This study aimed to define the molecular basis for 12 prenatal cases of Cri‐du‐chat syndrome (CdCS) and the potential genotyping‐phenotyping association.Karyotyping and single nucleotide polymorphism array analyses for copy number variants were performed.Nine cases had 5p terminal deletions and three had 5p interstitial deletions, and these cases had variable deletion sizes with partial overlapping. Phenotypically, besides intrauterine growth restriction (IUGR) and brain as well as heart abnormalities, hypospadias, and lung dysplasia were observed. Potential genetic causes for specific phenotypes in these cases were identified.This study defined the molecular bases for the patients of CdCS, which is important for genetic counseling for these families. The findings of present study expand the clinical features of CdCS in the fetal period, and provided important information for further refining the genotypic–phenotypic correlations for this syndrome. This study provides clinical and molecular characterization for 12 prenatal case of Cri‐du‐chat syndrome (CdCS) and genotyping‐phenotyping analysis for these cases. The findings from the present study are important for genetic counseling for the families of affected individuals, expand the clinical features of CdCS in the fetal period, and provide important information for further refining the genotypic–phenotypic correlations for this syndrome. CdCS is one of the most common chromosomal defect syndromes. It is estimated that CdCS occurs in 1 in 15,000–50,000 live birth infants Niebuhr, . ClinicaCTNND2; OMIM *604275) and semaphorin 5A  in 5p have linked to severe intellectual disability in individual affected with CdCS , NADH‐ubiquinone oxidoreductase subunits 6 , steroid 5 alpha‐reductase 1 , and/or ADAM metallopeptidase with thrombospondin type 1 motif 16  are associated with some specific phenotypes in CdCS.In this study, we defined the molecular bases for 12 prenatal cases of CdCS, and further identified that haploinsufficiency of iroquois homeobox 4  according to the manufacturer's instruction. Data from SNP array analysis was analyzed by using Chromosome Analysis Suite . All genomic coordinates were taken from the human reference sequence. Genes and Online Mendelian Inheritance in Man (OMIM) references were from RefSeq and OMIM entries, respectively  analyses were performed in cells in metaphase according to standard protocols  had developmental anomalies, and two cases  showed no apparent abnormality. Results of fetal ultrasound for case 6, 8, and 12 were not found. Among those with abnormal ultrasound findings, three cases  showed retarded embryo growth or intrauterine growth restriction (IUGR), five cases  displayed cerebellar hypoplasia, and two cases (4 and 7) exhibited CHD. In addition, fetus 3 also had lung tissue dysplasia, and both fetus 7 and 10 showed hypospadias. The detail information regarding the clinical findings is listed in Table Although fetus 11 appeared normal at 22 weeks of gestation by ultrasound testing, medical examination demonstrated that the father who carried the same 5p deletion had slight dysmorphic faces and mild intellectual disability. In addition, according to family history information, the first pregnancy of the same parents of fetus 11 was aborted because of the findings of CHD and diaphragmatic hernia at 7‐months gestation, and the second pregnancy was miscarried in the early stage.3.2Karyotyping by G‐banding were performed for 11 fetuses 2–12), and revealed that 9 of them except for fetus 9 and 11 showed 5p deletions. In addition, in accompany with the 5p deletion, duplication of 14q31.3‐q32.33 and 8p23.3‐p12 were detected in fetus 7 and fetus 8, respectively. Fetus 7 and 8 inherited the 5p deletion from the unaffected mother who underwent a balanced chromosome translocation between chromosome 5 and other chromosome. The karyotyping results are listed in Table –12, and Single nucleotide polymorphism array analysis identified 5p deletions in all 12 fetuses, and mapped the breakpoints for the deletion fragments. Nine cases had terminal deletions starting at 113,576 base pairs (bp) (position of the first probe from the used BeadChip in 5p) with distinct end breakpoints between 2,035,54 bp and 39,068,326 bp, and three cases had interstitial deletions. The smallest deletion encompassed 1.9 Mb and the largest spanned 39.0 Mb. The breakpoints for the duplicated fragment in fetus 7 and 8 were also mapped. SNP array analysis for the parents of the fetuses revealed that the 5p deletions in seven fetuses  were de novo, and in another five fetuses were inherited. The results of SNP array analysis are listed in Table 3.3TPPP; OMIM*608773), telomerase reverse transcriptase , IRX4, NDUFS6, ADAMTS16, CTNND2, NOP2/Sun RNA methyltransferase 2 , SEMA5A, membrane associated ring‐CH‐type finger 6 , dynein axonemal heavy chain 5 , and natriuretic peptide receptor C  among others to some specific feature of CdCS (Correa et al., Recent studies have linked the haploinsufficiency of tubulin polymerization promoting protein (4Cri‐du‐chat syndrome was first identified in three patients by Lejeune in 1963 (Lejeune et al., TPPP, NSUN2, and SEMA5A that localize in 5p13.3 have been demonstrated to play major roles in brain development (Blanco et al., CTNND2 that localize in 5p13.2 have also been linked with brain development (Hofmeister et al., NSUN2 and SEMA5A (Figure Abnormal brain development and function are one typical feature of CdCS patients in postnatal (Honjo et al., IRX4, NDUFS6, and DNAH5 that localize in this regions have been demonstrated to be critical for cardiovascular development (Nelson et al., IRX4 and NDUFS6, suggesting that haploinsufficiency of IRX4 and/or NDUFS6 lead to CHD.CHD has been reported in 15%–20% of patients of CdCS (Hills, Moller, Finkelstein, Lohr, & Schimmenti, SRD5A1 has been implicated as a candidate genetic reason for hypospadias. Notably, another two studies provided evidence that mutations of SRD5A2, instead of SRD5A1, were present in some boys with isolated hypospadias (Sun, Zhou, & Liu, SRD5A1 and SRD5A2 encode isoform 1 and 2 of 5α‐reductase that catalyzes the conversion of testosterone into the more potent androgen, dihydrotestosterone, and their protein products shared 50% sequence identity, but whether hemizygous deficiency each of them have similar effect in the development of hypospadias awaits future functional analysis.Hypospadias were rarely reported in patients of CdCS. Chen et al. reported a prenatal case with distal deletion involving 5p15.1 → pter that displayed cerebellar hypoplasia, hypospadias, and facial dysmorphisms (Chen et al., DNAH5 and ADAMTS16 were the deletion region. Li et al. demonstrated that the protein production of DNAH5 played an important role in the development of lung (Li et al., In the present study, we report a case of CdCS showing lung dysplasia of fetus 3 Figure B. The fe5p deletions with no apparent phenotype have been reported (Nguyen et al., 5p deletions mostly arise de novo, and 80%–90% of which are paternal in origin potentially due to breakage of chromosome 5 during gamete formation in males (Campbell et al., In summary, this study clarified the genetic diagnosis for 12 prenatal cases of CdCS from different families, which was important for guidance of the future pregnancy. In addition, this study provides more material for the clinical manifestation of CdCS in the fetal period, which is helpful for further analysis of the genotype‐phenotype correlation in CdCS. This study also provided evidence supporting the critical regions and candidate genes whose haploinsufficiency is causative for clinical features of CdCS.All authors declare that they have no commercial or other conflicting interests.Y Peng and H Wang designed the study. Y Peng and C Tang prepared the manuscript. J Pang and N Ma performed the SNP array analysis. Y Peng, J Liu, and S Yang interpreted the data of SNP array analysis. J Hu, H Xi, and Z Jia analyzed the karyotype study. X Huang performed the prenatal ultrasound testing.Written informed consent was obtained prior to investigation. The authors have no ethical conflicts to disclose.


However, the screening of nuclear attraction by inner core shells is more efficient for s than for p valence shells. The uniqueness of the 2p AO is explained by this differential shielding. Thereby, the present work paves the way for future physical explanations of the 3d, 4f, and 5g cases.The Periodic Table, and the unique chemical behavior of the first element in a column (group), were discovered simultaneously one and a half centuries ago. Half a century ago, this unique chemistry of the light homologs was correlated to the then available atomic orbital (AO) radii. The radially nodeless 1s, 2p, 3d, 4f valence AOs are particularly compact. The similarity of  2p or not 2p? Similarity of radii (and energies) of the atomic valence orbitals is the precondition for hybridization and hybrid bonding. In the Coulomb potential of H‐like atoms, the 2p orbital without a radial node is much smaller than 2s (2s≫2p), whereas higher p orbitals are comparably less contracted (ns≳np). The screening of nuclear attraction by the core shells is more effective for the core penetrating s orbitals, so that for the valence orbital radii of ordinary many‐electron atoms of the 2nd row, 2s≈2p, whereas in rows n>2, hybridization is less pronounced owing, i.a., to ns≪np. Knowing the trends along a series of related compounds is valuable for every chemist. Understanding the underlying physical reasons is even better. The individual chemical facts can be related to the general physical laws, stepwise, by first finding some generalizing empirical rule, and then rationalizing the rule by atomistic and electronic models that can be deduced from a quantum chemical basis.nsp valence atomic orbitals (AOs) of the p‐block elements, that is, of the canonical orbitals from Hartree–Fock or Dirac–Fock or Kohn–Sham levels of theory; which simulate the observable spatial and energetic changes in physical ionization and excitation processes.The unique chemical behavior of the 2p elements of the second period of the table of elements, in particular of B to F, is well known.12, 13In 2019, we celebrated the sesquicentenary of the first comprehensive tables of chemical elements, developed by Meyer, Mendeleev, and others in the 1860s.14, 15any vertical group of the periodic table to the exceptionally small radial extensions of the 1s, 2p, 3d, and 4f AOs. Orbital functions of all atoms had become known through the then‐possible routine atomic structure computations . The 1s, 2p, 3d and 4f AOs are characterized by having no radial nodes, in contrast to the nℓ AOs with higher principal quantum numbers n>ℓ+1, which have n−(ℓ+1) radial nodes . This so‐called Radial Node Effect is now linked to a well‐documented set of empirical chemical phenomena.. The energy quanta of radial and angular motions are equal . That does not hold for most other potentials such as for the harmonic oscillator, the particle in a box, or the linear potential . In general, there are large gaps between the s and p orbital levels. For instance, the energies of three‐dimensional harmonic vibrations in potential V(r)∼+r+2 ∼−r−1, see Eq. (1), Eq. (5)) are , remarkably independent of the cores: 1s2 for 2sp, or (1s2s2p)10 for 3sp, or (1s–3d)28 for 4sp, or (1s–4d)46 for 5sp. The radius patterns of H‐like or inner‐core AOs are contrasted with the valence AOs of the p‐block elements in Table Table We now investigate how the shielding of the nuclear attraction of the outer valence s and p AOs by the inner core shells emerges. Different relativistic Dirac–Fock and Kohn–Sham density functional calculations yield similar trends. Technical details are given in the Supporting Information (S.4). We increase the nuclear charge of an excited H atom and simultaneously add electrons.ns,np)1 (H*), obtaining Be ns2np2 (Be**) with an empty core and populated valence shells as in atoms C (n=2), Si (n=3), or Ge (n=4). Since the AO radii vary as ∼1/Z (compare Eq. (3)), we plot 1/⟨r⟩ versus Z to obtain nearly linear lines , Si n=, or Ge (2), Si n=, or Ge (σ→1), whereas screening by outer (Rydberg) shells would be even weaker (σ→0). The radii of the sp valence shells behave approximately as expected for Slater's nuclear screening by the next inner (σs=σp=0.85) and further in‐bound sp shells (σs=σp=1), corresponding to the flat lines on the right side of Figure ns than for np AOs in Figure σs≈0.7 and σp≈0.9 to 1.0, than by Slater's single averaged value of σs,p≈0.85. As a consequence, the valence s AOs of heavier p‐block atoms are eventually more contracted than the p AOs.Second, we populate the core shells until reaching C, Si, or Ge. Screening by inner shells is more efficient , and for group 14 atoms of the second to fourth period  are displayed in Table r⟩ and rmax ratios show similar trends as sketched in Figure ns versus np AOs by the (1s)2, (1s–2p)10, and (1s–3d)28 core shells reduces the hydrogenic rns/rnp ratio nQ throughout by approximately −40 %, whereas the s2p2 intra‐valence shell shielding is nearly an order of magnitude smaller (ca. −5 %). The two shielding effects interfere and damp each other (by ca. +15 %), which is not uncommon for two different ‘perturbations’. The joint screening reduction of nQ then sums up to approximately −40 %−5 %+15 %≈−30 %, throughout, as mentioned above , except r2s≈r2p in the second period (with dominant sp‐hybrid bonding). The hydrogenic relations are in contrast r2s≫r2p, and rns≳rnp for n>2. Although independent‐electron orbitals in principle do not exist by themselves in many‐electron systems,When periodic tables of elements were designed 150 years ago, it was realized that the first element in a column is special. A good century later, a large body of observed facts on the light homologs had been collected, classified, and related to the comparatively small radii of the 1s, 2p, 3d, and 4f valence AOs, resulting in different bonding schemes for the first versus the heavier homologs. Concerning the unique p elements of the second period, another half century passed until the final step of understanding is now achieved. The physical elucidation reveals why quantized motions of electrons in the nuclear Coulomb potential, screened by the other electrons. Canonical orbitals are conveniently chosen as a mutually orthogonal set. Owing to the mutual orthogonality and to the atomic potential V(r), the inner node positions of different radial orbitals of given ℓ occur at similar places, determined by the shape of the potential. The number of radial and angular orbital nodes and extrema is the number of quanta of the respective radial and angular motions. The number of quanta is required either by the Pauli principle and the occupied core shells, or by electronic excitation into a higher orbital above unoccupied ones. An orthogonality constraint on lower (occupied or unoccupied) AOs can be simulated by a pseudopotential, which is repulsive in the inner region. A pseudopotential is a useful tool for computations and for explanations, it does not represent a physical causal effect of mutual orthogonality.(1) The orbital set of an atom (or molecule) emerges as a coherent set, describing the r−1 are flattish at larger nuclear distances, with a narrow deep well at the center. This potential shape yields rather large orbital radii of the 2s, 3s, and 4s AOs, that is, significantly larger than the radii of orbitals 2p, 3d, 4f at the same energies. Radial motion (nodes) in a nuclear Coulomb potential moves the outer maximum of an orbital to larger radii  than the centrifugal force, in particular in the case of the 2s–2p orbital pair, where the 2p AO has no radial node. The radially nodeless 7i (ℓ=6) AO is smaller than 7s and even than 6s. For the 2s,2p AOs of H as well as of heavy atoms with occupied core shells, (rmax)2s/(rmax)2p is around 1.3, and ⟨r⟩2s/⟨r⟩2p is around 1.2.(2) Coulomb potentials ∼−ℓ=0 s states. For atomic ions Zq+, the effective Zeff varies from Zeff=Z at r=0 to Zeff=1+q at large r. The difference of the effective potential inside the atomic cores, compared with pure Coulomb potentials, leads to contracted s AOs (the Core Screening Effect). Slater's lowest‐order approximation of similar core screening for s and p valence AOs is not accurate enough for the chemical problems at hand. Although a basically Coulombic potential yields the orders ⟨r⟩2s≫⟨r⟩2p and ⟨r⟩3s≳⟨r⟩3p≳⟨r⟩3d for the inner core orbitals of all heavier atoms , the outer valence orbitals in the screened Coulomb potential follow the inverted order ⟨r⟩2s≲⟨r⟩2p, but ⟨r⟩3s≪⟨r⟩3p<⟨r⟩3d .(3) Radial oscillation samples the potential at large distances as well as in the nuclear vicinity, especially for the and radial patterns of the valence AOs determine the bonding behavior of an element.(4) Some update of chemical explanations appears appropriate. (a) The centrifugal force owing to a quantum of angular motion (corresponding to an angular node of the AO), is comparable to the expanding effect of a quantum of radial motion, represented by a radial node. Which is more effective depends on the shape of the effective potential in the core. (b) Electrons in valence s AOs of many‐electron atoms are less shielded and more attracted and contracted than their p counterparts. (c) Both the energetic 2 core of the 2nd period and the ‘standard sized’ (n‐1)p6 or (n‐1)p6d10 cores of the heavier nth periods codetermine the interatomic separations, and thereby the different valence‐orbital overlaps. More exotic core interpretations  have been refuted.[Other aspects may also be highlighted,30, 31and potential energy effects and their interplay need be analyzed together in physical explanations of chemistry. There is a tendency to explain covalent bonding electrostatically, whereas the electronic–kinetic aspect is physically dominating.Kinetic The relevance of each term  can only be judged on the basis of quantitative data, in particular in the more complicated cases of d and f orbitals. That is needed for a better future understanding of chemistry over the periodic table. Investigations of differential screening connected to the Radial Node Effect, as presented here for the p‐block, are still awaiting their turn to trace the physical origin of the chemical peculiarities of the 3d, and 4f, not to mention the hypothetical 5g block.r2s/r2p≈1, but nsr/npr<1 for n>2. The uniqueness of the 2p (as well as the 3d and 4f) block elements exhibiting the quantum primogenic effect plays a significant role in general chemistry. The effect is also essential for the topical support influence in heterogeneous catalysis.In summary, the 2p elements are known to be qualitative‐chemically different from their heavier congeners. The physical origin is the quantitative interplay of the electronic kinetic and potential energies of the valence orbitals: 2p has no radial node and little radial kinetic energy, thus 2p is radially contracted. All s orbitals are weakly shielded from nuclear attraction, thus 2s, 3s, 4s etc. are radially contracted. Therefore The authors declare no conflict of interest.As a service to our authors and readers, this journal provides supporting information supplied by the authors. Such materials are peer reviewed and may be re‐organized for online delivery, but are not copy‐edited or typeset. Technical support issues arising from supporting information (other than missing files) should be addressed to the authors.SupplementaryClick here for additional data file.


The morphological, physical, chemical properties of the nanocomposite have been investigated. The results revealed that the surface area of BiVO4, BiVO4/SiO2 and BiVO4/SiO2/GO was 11.13, 28.47 and 43.93 m2/g, respectively. The structural test by XRD proved that the nanocomposites were monoclinic phase of bismuth vanadate. Adsorption and photocatalytic degradation were two main mechanisms that strongly related to pollutant removal efficiency . The BiVO4/SiO2/GO nanocomposite obtained the greatest MB removal efficiency due to its high adsorption ability from high surface area, whereas the photocatalytic degradation was insignificant mechanism. In contrast, the relatively low adsorption ability of BiVO4/SiO2/GO nanocomposite was observed when the pollutant was phenol due to negative charge and high stability of phenoxide ions, then the photocatalytic degradation became the main mechanism for phenol removal. The phenol removal efficiency reached approximately 70% in 6 h with H2O2 assistance. The combination of SiO2 and GO improved the surface property of BiVO4-based photocatalyst, however the excessive combination ratio generated the excellent adsorbent material rather than the photocatalyst. Hence, the optimal combination ratio is essential to archive the greatest nanocomposite for photocatalytic application.The nanocomposite of BiVO Many technologies have been used to treat and reuse water source such as biological, chemical and physical processes to control pollutants leading to the sustainable development of environment. However, biological processes often require a previous acclimatization or special nutritional conditions, and many pollutants can form toxic or carcinogenic compounds which have a high bio-persistence. In the meantime, physical and chemical processes can generate second byproducts or transfer pollutants into other phases instead of destroying completely pollutants5. Therefore, advanced oxidation processes (AOPs) have been developed as a promising method for removing organic pollutants from aqueous environment, in which photocatalytic process using semiconductor is receiving much attention of researchers due to its advantages including environmental friendliness, no waste byproducts, complete degradation and mild operating conditions7. As the first photocatalyst discovered, titanium dioxide (TiO2) has been used widely to eliminate pollutants from water sources for many years8. However, the wide bandgap of TiO2 (3.2 eV) is only activated under UV region, which only occupies about 3–5% of solar light9. Therefore, visible light driven photocatalysts have been developed to use thoroughly the energy of solar light.In recent years, the water pollution has been causing serious problems influencing on the environmental crisis and the human health due to the release of organic wastewater from the rapid development of industries12, in which bismuth vanadate (BiVO4) has emerged as an effective photocatalyst due to its excellent properties including inexpensiveness, resistance to corrosion, high physicochemical stability and dispersibility14. Unfortunately, the photocatalytic activity of BiVO4 is restricted by the weak absorption and the poor migration of charged carriers16. In order to improve the photocatalytic activity of BiVO4, the combination of BiVO4 with appropriate materials is an effective way to enhance the specific surface area and the crystalline structure, leading to the increase of photocatalytic efficiency17. Among materials, silicon dioxide (SiO2) is known as an inexpensive material, well biocompatibility, large specific surface area, and easy functionalization; that can form p–n junction with BiVO4 to enhance the adsorptive ability and the separation of charged carriers20. In addition, graphene oxide (GO) is known as a 2D carbonaceous material which have large surface area (2630 m2/g), high conductivity and excellent mobility of charged carriers23. Therefore, GO is used as a favorable anchoring center to prevent the fast recombination of charged carriers, improving further the photocatalytic activity. As a result, it is expected that the combination of BiVO4, SiO2 and GO can generate a nanocomposite photocatalyst which have the best efficiency of photocatalytic activity.Among visible light driven photocatalyst, bismuth (Bi)-based photocatalysts have been attracting much attentions4/SiO2/GO nanocomposite by using solvothermal method. The sample was characterized by X-ray diffraction (XRD), scanning electron microscopy (SEM), and Brunauer–Emmett–Teller (BET) to clarify the morphology and crystalline structure. The photocatalytic activity was evaluated by the degradation of methylene blue (MB) and phenol under visible light irradiation. In addition, active species trapping test was also conducted to determine main species during the photocatalytic process of nanocomposite. Based on the obtained results, new insight of photocatalytic degradation of organic pollutant over BiVO4/SiO2/GO nanocomposite was found in the present work.Therefore, the objective of this work was to synthesize BiVO3)3·5H2O), ammonium metavanadate (NH4VO3), tetraethyl orthosilicate (SiC8H20O4), graphite flakes, sodium hydroxide (NaOH), sulfuric acid (H2SO4), potassium permanganate (KMnO4), hydrogen chloride (HCl), benzoquinone (C6H4O2), isopropyl alcohol (C3H8O), ammonium oxalate (C2H8N2O4), hydrogen peroxide (H2O2) were obtained from Sigma-Aldrich and were used as received without any further purification. The MB and phenol solution were prepared with DI water.Bismuth (III) nitrate pentahydrate  for 3 times, then with ethanol and DI water for several times to achieve pH nature. Finally, the obtained sample was dried at 80 °C for 24 h.In this work, graphene oxide was synthesized by Hummer’s method4-based nanocomposites were synthesized by using solvothermal method as follows: 5 mmol Bi(NO3)3·5H2O and 5 mmol NH4VO3 were stirred separately in 50 mL of ethanol for 30 min. These two solutions were then mixed together with the addition of 1 mL TEOS and 5 mL DI water for 1 h for the preparation of BiVO4/SiO2 core–shell. The pH of solution was adjusted to 5 by 2 M of NaOH solution. After that, the mixed solution was transferred into a Teflon-lined stainless steel and heated at 180 °C for 10 h. Finally, the resultant was washed with ethanol and DI water for several time, then dried at 80 °C for 24 h to achieve the final product. For the preparation of BiVO4/SiO2/GO nanocomposite, the obtained GO was sonicated in 20 mL of ethanol for 1 h in the first step. Secondly, 5 mmol Bi(NO3)3·5H2O and 5 mmol NH4VO3 were mixed in 100 mL of ethanol for 30 min, then followed by adding 1 mL of TEOS and 5 mL of DI water. In the third step, a calculated amount of GO solution was poured slowly into the above mixture. The fourth step is the pH adjustment of solution to 5 by NaOH of 2 M. Subsequently, the mixed solution was also heated at 180 °C for 10 h in the Teflon–lined stainless steel. After cooling, the BiVO4/SiO2/GO nanocomposites were obtained by washing with ethanol and Di water, which followed by drying at 80 °C for 24 h. In comparison, pure BiVO4 was also synthesized in the same conditions without the addition of SiO2 and GO.In the meantime, BiVOCrystal phase and structure of the as–synthesized samples were characterized by X–ray diffraction  using Cu Kα (λ = 1.54056 Å) radiation. The morphology was observed by transmission electron microscopy  and scanning electron microscopy . Brunauer–Emmett–Teller (BET) measurements  were performed to determine the specific surface area of samples.Typically, the photocatalytic experiments were performed at room temperature as follows: 0.05 g of photocatalyst was added into 50 mL of MB solution (3 ppm). The solution was stirred in dark condition for 30 min to achieve the adsorption–desorption equilibrium. After that, the solution was irradiated under visible light for 30 min by fluorescent lamp and the sample was collected every 10 min. The collected sample was centrifuged at 10,000 rpm for 15 min to remove the photocatalyst from dye solution. Finally, the concentration of dye solution was measured by UV–vis spectrophotometer  at the wavelength of 664 nm to determine the removal efficiency. Additionally, isopropyl alcohol, benzoquinone and ammonium oxalate was used as scavenger for the hydroxyl radical, super oxide, and hole respectively to determine main species during the photocatalytic process of MB.2O2 (35%) was stirred with 1 g/L of photocatalyst and for 30 min under dark condition. Afterwards, the mixed solution was irradiated under visible light for 360 min. The sample was collected at every 120 min followed by centrifugation, and then measured at 270 nm spectrophotometer  to determine the removal efficiency.Besides, the photocatalytic degradation of phenol was also conducted in this work. In which, 50 mL of 20 ppm phenol solution and a small amount of H4 nanoparticles, BiVO4/SiO2 core–shell and BiVO4/SiO2/GO nanocomposite. In which, the XRD peak of graphite was mainly observed at around 36° of 2θ, however this peak was moved to 11° of 2θ after graphite was oxidized to graphene oxide. In the meantime, Fig. 4 exhibited monoclinic phase corresponding to JCPDS No. 14-0688 which showed the highest photocatalytic activity17. Similarly, the diffraction peaks of BiVO4/SiO2 core–shell and BiVO4/SiO2/GO nanocomposite matched well with the monoclinic peaks of pure BiVO4 and no observation of other impurity peaks, this was due to the much lower content of SiO2 and GO in composite systems.Figure 4 and BiVO4/SiO2 were the aggregation of amorphous nanoparticles with the size of several micrometers. Therefore, they were adhered uniformly on the GO sheets to form BiVO4/SiO2/GO nanocomposite by the reduction of GO to graphene from hydrothermal reaction and the facilitation from the functional groups of GO nanosheets.The size and morphology of as–prepared samples were investigated via the SEM and TEM analysis, as shown in Fig. 4 nanoparticle adsorbed 35% of MB in the dark condition, and further degraded MB to 70% after 30 min of visible light irradiation. By coupling with SiO2, the adsorption of photocatalyst was increased to about 60%, leading to the final MB removal efficiency of 84%. In the meantime, the BiVO4/SiO2/GO nanocomposite showed the highest final MB removal efficiency of 94% with the high adsorption ability of 82%. The reason for excellent MB removal performance of BiVO4/SiO2/GO nanocomposite was that the specific surface area and the pore size were increased significantly by coupling with SiO2 and GO, as determined by BET characterization , which belonged to the average pore size diameter as reported in Table 4/SiO2/GO composite were 43.93 m2/g and 0.15 cm3/g; while those of single phase BiVO4 were 11.13 m2/g and 0.03 cm3/g, respectively. The quantity N2 adsorbed as well as other surface properties were found to increase as the SiO2 and GO were gradually added to BiVO4. The improvement of various surface properties of BiVO4/SiO2/GO were expected to benefit the pollutant to get adsorbed on the photocatalyst surface, which subsequently improved the photocatalytic process under light irradiation.Figure 4/SiO2/GO nanocomposite was analyzed further, as in the supplement  could not make an excellent photocatalyst, instead it generated the excellent adsorbent in the present work. This is summarized in Fig. 4/SiO2 and BiVO4/SiO2/GO was adsorption, whereas that of BiVO4 was photocatalysis, as calculated in the supplement , was measured in the treated phenol solution to confirm the complete mineraliation and/or the occurance of intermediates. The initial COD concentration was 80 mg/L and it was decreased to approximately 46, 25 and 10 mg/L for BiVO4, BiVO4/SiO2 and BiVO4/SiO2/GO respectively in the 6 h-treated phenol solution. Therefore, the phenol molecule was degraded to small organic compounds, especially using BiVO4/SiO2/GO composite. The possible intermediates during phenol degradation were hydroquinone, benzoquinone, catechol and organic acid26. It should be noted that the existing H2O2 as interfering substrate could have a positive error effected on COD analysis27. It is important to be noted that the prove of present hydroxyradical is improtant as presented by several works28. In addition to the valuation of photocatalytic activity, the active species generated during the MB photocatalytic degradation were investigated by using scavenger as shown in Fig. Due to the theoritical photocatalytic mechanism, the organic pollutant  was degraded by hydroxyl radical of photocatalyst and mineralized to CO4 was increased by the addition of AO and IPA. Unfortunately, this result was disagreement with previous studies because the recombination rate of electron–hole pairs of as–prepared BiVO4 was too fast, leading to less formation of hydroxyl radicals. Therefore, scavenger played as intermediate center which can reduce the recombination rate of electron–hole pairs, leading to the increase in photocatalytic degradation. In the meantime, not much change was observed in the photocatalytic process of BiVO4/SiO2 core–shell and BiVO4/SiO2/GO nanocomposite, because the scavenger can be adsorbed by SiO2 and GO layers, leading to the slight decrease in photocatalytic degradation. These results suggest that the scavenger test should be only used in the photocatalytic process which has much formation of active species. Figure 4 nanocomposite, BiVO4/SiO2 core–shell and BiVO4/SiO2/GO nanocomposite in the presence of scavenger.The obtained results indicated that the photocatalytic degradation of BiVO4/SiO2/GO nanocomposite was synthesized successfully by one–step solvothermal method. Nanocomposite was formed by the uniform adhesion of SiO2 and BiVO4 on GO nanosheets. Due to the low content of SiO2 and GO, the BiVO4/SiO2/GO nanocomposite exhibited the same XRD peaks of monoclinic BiVO4 without others contamination phase. The BiVO4/SiO2/GO showed the highest surface area of 43.93 m2/g, conversely the BiVO4 had only 11.13 m2/g. The BiVO4/SiO2/GO nanocomposite showed the higher adsorption ability rather than the photocatalytic degradation for MB removal. The enhancement of photocatalytic degradation was observed for phenol removal under H2O2 assistance. The BiVO4 nanoparticle still obtained the best photocatalytic ability than BiVO4/SiO2 core–shell and BiVO4/SiO2/GO nanocomposite. Although both SiO2 and GO were great property materials which able to improve the photocatalytic ability of BiVO4, the improper combination ratio caused the nanocomposite containing high adsorption ability and low photocatalytic degradation, as presented in this work. This is very important to be noted that the optimal combination ratio is essential to archive the greatest nanocomposite for photocatalytic application.In the present work, the BiVOSupplementary Information.


The results allow us to derive a model of the molecular mechanism of substrate binding to SBD2 and associated conformational changes.Substrate‐binding domains (SBD) are important structural elements of substrate transporters mediating the transport of essential molecules across the cell membrane. The SBD2 domain of the glutamine (GLN) transporter from bacteria consists of two domains D1 and D2 that bind GLN in the space between the domains in a closed conformation. In the absence of ligand, SBD2 adopts an open conformation with increased domain distance. In molecular dynamics (MD) simulations in the absence of ligands, no closing of the open conformation was observed on the MD time scale. Addition of GLN resulted in several reversible binding and unbinding events of GLN at the binding site on the D1 domain but did not induce domain closing indicating that binding and global domain closing do not occur simultaneously. The SBD2 structure remained in a closed state when starting from the GLN‐bound closed crystal structure and opened quickly to reach the open state upon removal of the GLN ligand. Free energy simulations to induce opening to closing indicated a barrier for closing in the absence and presence of ligand and a significant penalty for closing without GLN in the binding pocket. Simulations of a Leu480Ala mutation also indicate that an interaction of a C‐terminal D1‐tail This technique has already been used to study the dynamics of GLN binding proteinsWe use molecular dynamics simulations on the SBD2 of the GlnPQ importer from the gram‐positive bacterium 22.1Unrestrained molecular dynamics (MD) simulations were started from the open SBD2 state (PDB: 4KR5). In the absence of GLN ligands the root‐mean‐square deviation (RMSD) with respect to the start structure stayed in the range of ~2–3 Å within 1.8 μs simulation time and no indication of spontaneous global domain closing. The RMSD with respect to the closed structure remained at a high level of ~9–12 Å . In a seThe lifetime of these complexes was much longer (ranging from 100 to 1000 ns) than for the nonspecific placements distributed over the whole surface of the protein. After dissociation of one GLN, replacement with another GLN was observed two times indicating independent and uncorrelated binding events.lig < 2.5 Å . The analysis of individual contributions revealed Arg333 to play the dominant role in stabilizing GLN binding by a salt bridge of the terminal COO− through the guanidinium group of Arg333. The backbone carbonyl of Gly326 as well as the hydroxyl group of Ser328 also contribute significantly to ligand binding by forming frequent hydrogen bonds to the GLN alpha‐amino group. The bound GLN side chain amino group forms stabilizing hydrogen bonds with Asp267 or Ser325 as well as non‐polar interactions with the two opposing benzyl groups of Phe270 and Phe308.bound = 0.67 and Punbound = 0.33. With a ligand concentration of Cligand = 25 mM a standard binding free energy of GLN binding of ΔG = −2.6 kcal/mol was obtained. To further analyze the dynamics and intermediates of the ligand binding process we investigated each association and dissociation event at higher time resolution. We recorded three distances in distinct regions of the binding site that characterize the bound state  with GLN in the binding cleft between D1 and D2 domains indicated stable binding and also no tendency for global opening on the time scale of 1 μs . HoweverKQP with 418‐427, especially in the realm of the key residue Leu480, which we will discuss in more detail subsequently  to identify the correlation in the backbone dynamics of this opening transition and projected the trajectory onto the first two eigenvectors Figure , S4. Thay Figure . is still slightly visible…)418‐427) region when the protein is in an open state. All the residues with reduced mobility in the absence of GLN  contribute to the formation of a hydrophobic “lock,” that stabilizes the open state of SBD2  of each residue gives a measure of residues that showed different mobility in the two domain arrangements Figure . Typical2 Figure . Note, t2 Figure .2.3471‐484 residues of D1 form an interaction with D2's α‐helical418‐427 residues, to serve as a “lock,” stabilizing the open conformation. Despite the fact that other D1 residues  as well as tyrosine (Tyr344) in the β‐sheet hinge region also participate in this hydrophobic “locking” mechanism it is this close contact between the two helices which seems to be crucial in the open SBD2 state. Interestingly, this type of D1/D2 contact has been found in several SBDs . This transition also resulted in the disruption of the contact between C‐taild Figure  and the d Figure . The fird Figure .2.4The unrestrained MD simulations give important qualitative insights into the substrate dependent local and global dynamics of the SBD2 system. However, important transitions such as the open‐to‐close transition of the SBD2 protein upon ligand binding was only observed for a Leu480Ala mutation but not for the wild type indicating a substantial energy barrier not crossed within the simulated time scales. In order to investigate the free energy profile for open‐close domain transitions we performed extensive HREUS simulations on the system employing a center‐of‐mass distance reaction coordinate between the two subdomains D1 and D2 that allows to distinguish the open and closed state and correlated with the PC1 of the observed transition.471‐484‐D2 helix418‐427 contact is formed/disrupted  resulted in rapid (barrier less) closing and it also destabilizes the open state such that occasionally closed states are sampled in the absence of ligand on the present MD timescale .Another major result of the present study is the observation that the D1‐tailThe barrier for the transition from the closed SDB2 state to the open state is found to be significant in case of a bound GLN but considerably smaller for SDB2 without a ligand. Hence, the prediction from this result is that the lifetime of the closed‐form should be longer in the presence of a ligand than without a ligand. However, smFRET studies show that the addition of GLN increases the frequency for open‐to‐close transitions.44.1Lactococcus lactis−1·Å−2) on the protein non‐hydrogen atoms during 1 ns simulation time. The restraints were gradually removed for another 1 ns followed by unrestraint production simulations of more than 3 μs. All bonds involving hydrogens were kept at optimal length using Shake.The crystal structures of the open (PDB:4KR5) and the GLN bound closed SBD2 protein (PDB:4KQP) from 4.2−1·Å−2 was generated with an equidistant spacing of 1 Å covering distances from 6 Å up to 21 Å. During the replica exchange process exchanges between neighboring US windows were attempted every 1 ps reaching an acceptance rate of 25–45%. The equilibrium distance for the reaction coordinate in the unrestrained simulations of closed and open SBD2 structure was 7.7 Å and 20 Å, respectively. H‐REUS simulations were carried out in the presence and absence of GLN in the binding pocket on the D1 domain. In each case one simulation was started from the open SBD2 configuration and the other starting from closed SBD2, resulting in a total of four H‐REUS simulations. The overall simulation time for the ligand‐bound state amounted to ~15.1 μs for all 16 US windows, where each US window was simulated for ~400 ns for the first simulation and ~ 540 ns for the second simulation, respectively. For the unbound state the total simulation time amounted to ~16.6 μs, where each US window was simulated for ~300 ns for the first simulation and ~ 741 ns for the second simulation. The simulated distributions along the reaction coordinates for the ligand‐bound and unbound state were analyzed by employing the weighted histogram analysis method (WHAM)Umbrella sampling (US) simulations coupled with Hamiltonian Replica exchanges (H‐REUS) between neighboring US intervals4.3Average interaction energy calculations on the unbiased trajectories have been conducted using the MMPBSA trajectory post processing method,Conceptualization, Martin Zacharias; Investigation, Maximilian Kienlein; Writing, Maximilian Kienlein and Martin Zacharias; Resources, Martin Zacharias, Supervision, Martin Zacharias, Funding Acquisition, Martin Zacharias.Appendix S1: Supporting informationClick here for additional data file.


Leucine‐rich repeat–coupled receptor 6 (LGR6) is a marker of the skin, nails, and other types of adult tissue stem cells and has been widely found to be related to the development and progression of a variety of cancer types. The clinical significance and biological function of LGR6 in esophageal squamous cell carcinoma (ESCC) have not been determined.The expression of LGR6 at the transcriptional level was analyzed by searching the TCGA and UCSC data sets. Immunohistochemistry, WB, and q‐PCR were used to detect the expression of LGR6 in ESCC and adjacent normal tissues. LGR6 PPI networks and KEGG pathways were used to analyze the potential biological functions of LGR6.The expression of LGR6 in ESCC tissues was significantly higher than that in normal tissues and was negatively correlated with the differentiation degree of ESCC and the prognosis of the patients but not closely correlated with the TNM stage of ESCC. PPI networks showed that LGR6 had a close interaction with RSPO1, RSPO2, RSPO3, and RSPO4. KEGG pathway analysis showed that LGR6 activated the Wnt/β‐catenin signaling pathway by binding with RSPO ligands to promote the progression of ESCC.LGR6 can serve as a potential diagnostic and prognostic marker for ESCC. AJCCAmerican Joint Committee on CancerESCCesophageal squamous cell carcinomaKEGGKyoto encyclopedia of genes and genomesLGR6leucine‐rich‐repeat‐coupled receptor 6PPIprotein‐protein interactionSTRINGsearch tool for the retrieval of interacting genesTCGAthe cancer genome atlasUCSCUniversity of California Santa CruzWBWestern blot1Esophageal cancer is one of the most common malignant tumors in the world, and its incidence ranks seventh among those of all malignant tumors.Leucine‐rich repeat‐containing G protein–coupled receptors (LGRs) are a subgroup of the seven‐transmembrane G protein‐coupled superfamily that regulates various physiological processes associated with various diseases,LGR6 plays a pivotal role in adult stem cells, which are markers of various types of adult stem cells in the skin, nails, and a group of basal and intraluminal progenitors that induce luminal tumorigenesis.In this study, we evaluated the clinical significance of LGR6 expression in 102 patients with ESCC and analyzed its association with clinicopathological features and patient survival. We explored the functional effects and potential molecular mechanisms of LGR6 on ESCC progression by using the University of California Santa Cruz (UCSC) and the Cancer Genome Atlas (TCGA) data, constructing a protein‐protein interaction (PPI) network and performing Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis.22.1During the surgical resection of esophageal cancer at Fujian Medical University Union Hospital  from January 2009 to December 2011, ESCC samples and their corresponding non‐tumor esophageal tissues were collected (n = 102). Tissues were immediately frozen in liquid nitrogen and stored in a −80°C freezer or fixed in 10% formalin for paraffin embedding. All samples were collected with informed consent of the patients, and the study was approved by the institutional review committee and regulatory authorities of Fujian Medical University.The pathological diagnosis was based on the World Health Organization (WHO) classification, and the clinical‐pathological staging was based on the American Joint Committee on Cancer (AJCC) classification. No patient received chemotherapy or radiation before surgery. The median follow‐up time for overall survival was 43.5 months (range 1‐60 months). The characteristics of the 102 patients with ESCC are summarized in Table 2.2Total RNA was extracted from frozen tissue using TRIzol reagent (Ambion) according to the manufacturer's instructions, and 1 mg of RNA was reverse transcribed for first complementary DNA strand synthesis using a miScript Reverse Transcription Kit (Qiagen). Real‐time quantitative PCR was performed using a SYBR Premix EX Taq Kit (Takara). The relative mRNA expression of LGR6 was detected with the 2−ΔΔct method using specific primers, and its expression level was normalized to that of endogenous β‐actin. All primers were designed by BioSune Biotechnology Co., Ltd. The sequences of the primers used are as follows: LGR6: 5′‐TGGGGAACCCTCTGCTACAG‐3′ (forward) and 5′‐CAGGTACTGGAATGCCGATCT‐3′ (reverse); and β‐actin: 5′‐CTCCATCCTGGCCTCGCTGT‐3′ (forward) and 5′‐GCTGTCACCTTCACCGTTCC‐3′ (reverse).2.3Tissues were lysed in Western and radioimmunoprecipitation assay (RIPA) tissue lysis buffer (Beyotime) supplemented with phenylmethylsulfonyl fluoride  on ice for 30 minutes and then centrifuged at 12 000 rpm at 4°C for 10 minutes. The supernatant was collected as the total protein, and then, the protein concentration was determined using a BCA Protein Assay Kit (Thermo Scientific). The same amount (60 μg) of protein in each well was separated by 10% sodium dodecyl sulphate‐polyacrylamide gel electrophoresis (SDS‐PAGE) and transferred to a 0.45‐μm polyvinylidene fluoride (PVDF) membrane . The PVDF membrane was then blocked with 0.5% bovine serum albumin (Amresco) followed by incubation overnight at 4°C with primary antibodies against LGR6  and β‐actin . The PVDF membrane was then washed three times for 10 minutes each in Tris‐buffered saline Tween (TBST) at room temperature and then incubated with the secondary antibody for 1 hour at room temperature. The protein imprint was developed by enhanced chemiluminescence (Lulong Biotech).2.4ESCC and adjacent normal tissues from 102 patients were fixed with formalin and embedded in paraffin, followed by IHC studies using a human anti‐LGR6 antibody . The degree of LGR6 staining was calculated and quantified according to the following aspects: score of stained tumor cells  multiplied by the staining intensity score  to obtain the final score. A final score of 3 or lower was classified as low expression, and a final score of 4‐12 points was classified as high expression. The above scoring process was completed by two pathologists (Xinjian Lin and Wannan Chen) in an independent blinded manner. Before an agreement was reached, the two pathologists discussed any inconsistent scores.2.5http://genome.ucsc.edu/) and TCGA (http://cancergenome.nih.gov) databases.Differences in the mRNA expression of LGR6 in different normal tissues, as well as in different cancer tissues and the corresponding adjacent normal tissues, were investigated by searching the UCSC (2.6http://www.string-db.org/), a PPI network related to LGR6 was established. The interactions procured included known interactions and predicted interactions.Using the Search Tool for the Retrieval of Interacting Genes (STRING) database (2.7https://www.kegg.jp/kegg/pathway.html), and the function of the LGR6 gene was analyzed.The signaling pathways involving LGR6 were determined with the KEGG pathway database (2.8t test was used to test the significance of the differences between each of the two groups. All data are expressed as the mean ± standard deviation (SD) of three independent assays. The association between LGR6 expression and the clinicopathological features of ESCC patients was analyzed using the Pearson chi‐square test. The survival curve was plotted using the Kaplan‐Meier method. When P < .05, the difference was considered to be significant.Statistical analysis was performed using SPSS 24.0 for Windows . Student's 33.1First, we searched the UCSC data set. Among the 53 tissues obtained from 8555 samples (570 donors), LGR6 mRNA expression was highest in the artery‐aorta, and its expression in esophageal tissue was relatively low Figure . Next, wt test P < .001; Figure We used IHC to study LGR6 expression in ESCC tissues and the corresponding adjacent normal tissues (NT) in 102 patients. Representative staining images of LGR6 expression are shown in Figure 3.2P = .183), age (P = .181), tumor node metastasis category , or clinical stage (P = .112). LGR6 expression was significantly negatively correlated with 5‐year survival (P < .001) and differentiation status  patients showed low LGR6 expression, and 63 (61.76%) showed high LGR6 expression. LGR6 expression had no obvious correlation with clinical‐pathological variables, including sex , and LGR6 primarily participates in the Wnt/β‐catenin signaling pathway to exert its biological functions. LGR6 interacts with its ligand RSPO1‐4 to activate the Wnt/β‐catenin signaling pathway through phosphorylation, thereby affecting multipotent biological functions.The Wnt/β‐catenin signaling pathway plays a key role in the pathogenesis of various human diseases and tumors.However, the function of LGR6 in different cancers remains controversial.Hauser AS and Lappano R et al reported that G protein–coupled receptors and membrane signaling proteins including LGR6 are good candidates for cancer‐targeting molecular therapies.The limitation of this study is that there was no in‐depth study of the molecular mechanisms of LGR6 in the development and progression of esophageal cancer, which is where further research and exploration are needed in the future.In summary, this study confirmed for the first time that LGR6 is highly expressed in ESCC tissues and that increased expression of LGR6 is associated with a poor prognosis of ESCC patients. LGR6 may promote ESCC progression by activating the Wnt/β‐catenin signaling pathway. These findings provide a basis for the potential application of LGR6 as a biomarker for early diagnosis and as a target gene for early therapeutic intervention.The authors have no conflicts of interest to disclose. Click here for additional data file.


Europium ions are distributed throughout the SnO2 film during the formation process of SnO2, and they can diffuse directionally through the SnO2/perovskite interface into the perovskite, while most of the europium ions remain at the interface. Under the synergistic effect of distributed Eu3+ in the SnO2 and aggregated Eu3+ at the interface, the electron mobilities of ETLs are evidently improved. Meanwhile, diffused Eu3+ ions passivate the perovskite to reduce trap densities at the grain boundaries, which can dramatically elevate the open‐circuit voltage (Voc) of PSCs. Finally, the mainly PSCs coated on SnO2:Eu3+ ETL achieve a power conversion efficiency of 20.14%. Moreover, an unsealed device degrades by only 13% after exposure to ambient atmosphere for 84 days.So far, most techniques for modifying perovskite solar cells (PSCs) focus on either the perovskite or electron transport layer (ETL). For the sake of comprehensively improving device performance, a dual‐functional method of simultaneously passivating trap defects in both the perovskite and ETL films is proposed that utilizes guidable transfer of Eu 2 film and diffuse into perovskite, while most of Eu3+ remain at the interface. Under the synergistic effect of distributed Eu3+, the electron mobility of ETL is improved and the trap density of perovskite is also reduced.A dual‐functional method of simultaneously passivating trap defects in both perovskite and electron transport layer (ETL) films is proposed. Europium ions distribute throughout SnO Recently, the certified power conversion efficiency (PCE) of perovskite solar cells (PSCs) has risen steeply to 23.7%,10 how Various techniques, such as encapsulation, ultraviolet filtration, and modification have been used to delay the degradation of perovskite materials under the stress of environmental and device operational factors for maintaining long‐term stability of PSCs. Additionally, methods that introduce additives into perovskite films to promote PCE are widely used. For instance, goethite quantum dots interact with iodine, lead and methylamine, resulting in the retardation of crystallization kinetics to achieve perovskite films with high crystallinity and large grain size; Imidazole sulfonate zwitterions are introduced to regulate the crystal orientation of MAPbI3 film so it is highly ordered to passivate trap states; and the conjugated polymer poly(bithiophene imide) is incorporated within grain boundaries to improve the crystallinity of perovskite film for reducing its defects.Most of the reported methods aiming to improve either or both the PCE and stability of PSCs focus on optimizing the perovskite or electron transport layer (ETL). Regarding perovskite photon absorber layers, their soft crystal lattices tend to easily deform, particularly under various stresses, such as moisture, oxygen, and ultraviolet light exposure, and even under the electric field and thermal stress during device operation.17 Var2, using ‐Phenyl C61 butyric acid to modify ZnO, or doping TiO2 with Sm3+ and Eu3+ ions. Fabricating an ETL with organic chemicals or rare‐earth ions can not only tune the Fermi level of the ETL to better match the conduction band of the perovskite for facilitating charge carrier transfer but also modify the interface between the perovskite and the ETL to induce the perovskite to crystalize with better quality and larger grain size. However, more effective and convenient techniques need to be developed to improve both the perovskite and ETL by simultaneously repairing the different trap defects in the photon absorber and ETL, finally achieving effective photon‐induced charge carrier separation and transfer for higher PCE. This one‐step technique can reduce the cost of PSC engineering by a significant margin.Besides optimizing the photon absorber, as an important part of a PSC, the ETL must possess high electron mobility to extract photo‐induced carriers because effectively transferring carriers to the external circuitry can promote the PCE of devices. Meanwhile, a suitable ETL should present decent optical transmittance for ensuring enough light reaches the perovskite absorber. Various strategies for optimizing ETLs are reported, such as ethylene diamine tetraacetic acid complexing SnO2,23 usi0 and reduce I0 defects simultaneously in MAPbI3 thin films, and the elimination of both Pb0 and I0 defects promotes the photovoltaic properties of MAPbI3 PSCs with PCE up to 19.67%. This MAPbI3 film is deposited by a traditional two‐step method. In this process, Eu(acac)3 additive is added to the PbI2/DMF (dimethylformamide) precursor solution. In addition to modifying the perovskite materials, Eu3+ and Sm3+ co‐doped TiO2 are prepared by the pulsed laser deposition method. The incorporated Eu3+ ions in cooperation with Sm3+ optimize the TiO2 ETL, achieving higher electron extraction and lower interfacial recombination; therefore, power conversion efficiency as high as 19.01% can be obtained for a MAPbI3 solar cell. Evidently, for the purpose of simultaneously reducing the trap defects in perovskite and ETL films, europium additive is a good choice; however, the above‐discussed preparation methods present restrictive europium oxidation effects or high‐temperature/cost synthesis processes.Europium ions can perform as a redox shuttle to selectively oxidize Pbo 19.67%.10 Thi3+ incorporation in both the ETL and perovskite in one step. Europium and tin ions are simultaneously deposited to form SnO2:Eu3+ film on FTO (F‐doped SnO2) glass. We observed directional diffusion of Eu3+ from the SnO2 ETL to the MAPbI3 perovskite film, which leads to accumulation of large amount of Eu3+ at the perovskite/ETL interface. Eu3+ ions synergistically eliminate the trap defects in both the ETL and perovskite films, resulting in an improved electron mobility of the SnO2 and grain boundary passivation within MAPbI3 films. The champion fabricated PSC attains a PCE as high as 20.14%, and, when exposed to the ambient atmosphere, the unsealed PSC presents a slow degradation by only 13% after 84 days. All these results indicate that our dual‐functional technique of europium passivation is extremely effective and convenient.We demonstrate a guidable transfer method to achieve Eu22 films are different, the reflectance can be influenced by the modification of SnO2 films. Doping with Y3+ ions improves the antireflection ability of the SnO2 films and results in an increase in the optical transmittance in the region of 350 to 625 nm for the substrates. The optical transmittance spectra of SnO2 and SnO2:Eu3+ films on FTO substrates are shown in Figure 3+ ions can improve the optical transmission properties of FTO/SnO2 substrates. In both the 350–410 nm and 440–600 nm regions, the optical transmittances of FTO/SnO2 substrates are enhanced with increasing concentration of Eu3+ dopant.Since the refractive indices of FTO substrates and SnObstrates.26 The2:Eu3+ films, which should be related to the variable morphology of the homogeneously distributed SnO2:Eu3+ grains. Thus, the top‐view scanning electron microscopy (SEM) images of SnO2 and SnO2:Eu3+ films were measured and are shown in Figure S1, Supporting Information. The images show that the SnO2 film appears to be flat, uniform and pinhole‐free. After the introduction of Eu3+ ions, many nanoparticles appear on the grain surface. Figure S2, Supporting Information shows atomic force microscopy images of SnO2 and SnO2:Eu3+ films deposited on FTO substrates. The calculated data reveal that the root‐mean‐square roughness decreases from 29.9 to 22.1 nm with Eu3+ doping. Note that the smoother surface is beneficial to film‐forming of the perovskite layer.The variation of optical transmittance is caused by the reduction of light scattering on the surface of SnOte layer.233+and matrix SnO2. As shown in Figure −1 belong to the O—Sn—O symmetric stretch, and the peaks at 895 cm−1 are attributed to the O—O stretching about vibration of the oxygen adsorbed on the surface of SnO2 films. All the weaker peaks at ≈2180, ≈2027, and ≈1977 cm−1 are due to Sn—O stretching vibrations. All of these absorption peaks are unaffected by Eu3+ doping; however, for the SnO2:20% Eu3+ sample, the characteristic asymmetric stretching peaks on the SnO2 surface shift to 486, 446, and 434 cm−1, which demonstrates that Eu3+ ions might enter into the SnO2 crystal lattice and affect the SnO2 surface.FTIR spectra is used to study the interaction between the dopant Eubrations.27 All3+ and SnO2, the XPS spectra for SnO2 and SnO2:20% Eu3+ films are measured and shown in Figure 2 films, the shifts of ≈ 0.2 and 0.05 eV of the Sn 3d and O 1s peaks, respectively, can be observed in the SnO2:20% Eu3+ films, indicating that the Eu3+ dopant affects the SnO2 surface. Furthermore, the presence of trivalent Eu3+ can be confirmed by the observed binding energies at ≈1167.2 and 1139.8 eV, which are attributed to the 3d3/2 and 3d5/2 orbitals of Eu3+.To further clarify the interaction between Eu2 and SnO2:20% Eu3+ were measured and shown in Table S1, Supporting Information, respectively. The average Hall coefficients indicate that SnO2 and SnO2:20% Eu3+ are both well ETL films. Meanwhile the recorded resistivities, mobilities, and carrier concentrations prove Eu3+ doping can reduce resistivity and promote mobility in SnO2 films. It is known that the electron mobility of ETLs is the key factor for the performance improvement of PSCs. The various ETLs are also measured by the space charge‐limited current method, and the results shown in Figure 2:20% Eu3+ is 1.48 × 10−5 cm2 V−1 s−1, which is about eight larger than that of SnO2 (1.97 × 10−6 cm2 V−1 s−1). High electron mobility can effectively promote electron transfer in an ETL, thus the charge consumption at the interface between the ETL and perovskite is reduced, finally resulting in improved efficiency of PSCs.The electrical properties of semi‐conductive films can be characterized by the Hall Effect measurements, such as conductivity type, resistivity, mobility and carrier concentration. The average Hall coefficient, resistivity, mobility, and carrier concentration of SnOt method,23 and2/perovskite sample, significant PL quenching is observed with increasing Eu3+ concentration in the samples on SnO2:Eu3+ ETL substrates. The data demonstrate optimized SnO2:20% Eu3+ presents the most appealing merits with the highest electron mobility. Figure τ1 and a fast decay component τ2. Generally, τ1 is attributed to the radiative recombination of free carriers captured by the traps in bulk materials and τ2 originates from the quenching of charge carriers in the transportation process through the interfaces. The FTO/SnO2/perovskite sample presents a long τ2 lifetime of 37.55 ns, but it quickly decreases with increasing Eu3+ in SnO2 films. Smaller τ2 dominating PL decay indicates that electrons can be effectively extracted from the perovskite layer to the ETL with minimal recombination loss at the interface. In the sample of perovskite deposited on SnO2:20% Eu3+, τ1 was increased slightly to 7.65 ns, but τ2 was considerably shortened to 3.53 ns; moreover, the lifetime contributions of τ1 and τ2 are 13.05% and 86.95%, respectively. These results indicate that the Eu3+ dopant in SnO2:20% Eu3+ film leads to suppressed charge carrier recombination at the interfaces, which remarkably dominates the overall charge carrier transport process. Moreover, sharply decreased τ2 indicates that the carrier transfer efficiency at the interfaces can be significantly promoted by doping Eu3+ into SnO2. To summarize, the reduced loss of charge carriers at the interfaces drastically improves the carrier transfer efficiency in SnO2:20% Eu3+, which can be considered as a potential electron extraction layer for planar‐type PSCs.The PL spectra of the perovskite deposited on different ETL substrates are presented in Figure 3 perovskite films can simultaneously reduce Pb0 and I0 defects for achieving high PCE, and they more easily concentrate at surfaces and grain boundaries or intercalate into two adjacent lattices. In our research, X‐ray diffraction (XRD) patterns of MAPbI3 on various ETL substrates (SnO2 and SnO2:Eu3+) in Figure 2:Eu3+ films into MAPbI3 perovskite films. When the europium ion concentration in SnO2 films is adjusted from 5 to 20 mol%, an obvious shift of the MAPbI3 (110) diffraction peak is observed. Because the radii of Eu3+ and Pb2+ are 94.7 and 119 pm, respectively, the shifts of the diffraction peak indicate that Eu3+ may prefer to intercalate into two adjacent lattices than to enter into the perovskite crystal lattice, in accordance with the reported density functional theory result. When the doping concentration of Eu3+ exceeds 20%, excess Eu3+ might enter Pb2+ sites of the perovskite crystal lattice. Therefore, the shift of diffraction peak would reverse, and the corresponding photovoltaic properties of PSCs would be affected.The doped europium ions in MAPbIlattices.10 In 2 and perovskite/SnO2:20% Eu3+ films, respectively, and their spatial distribution images are presented in Figure 2 (or SnO2:Eu3+) films. It is observed that Eu3+ ions are evenly distributed in the SnO2 film, but they tend to aggregate at the interface between the perovskite and SnO2:20% Eu3+ films, and subsequently, through the process of diffusion, a few Eu3+ ions enter the perovskite film. Therefore, the shifts of the asymmetric stretching Sn—O peaks in the FTIR spectra /ETL/perovskite/PCBM (phenyl‐C61‐butyric acid methyl ester)/Ag, and the corresponding dark current–voltage (I–V) curves are shown in Figure S5, Supporting Information. At low bias voltage, the linear correlation shown as red lines indicates an ohmic response. When the bias voltage increases above the kink point, the current suddenly increases with a nonlinear correlation (cyan line), which reveals that the traps in the perovskite film are totally filled. The bias voltage corresponding to the kink point between the linear and nonlinear correlation is defined as the trap‐filled limit voltage (VTFL). The trap densities (Nt) of the perovskites on different ETLs are calculated by the equation Nt = (2VTFLεε0)/(eL2), where ε and ε0 are the relative dielectric constant for MAPbI3 perovskite and vacuum permittivity, respectively, e is the electron charge and L is the thickness of the MAPbI3 perovskite film. It is obvious that the trap densities of the perovskites were reduced from 1.69 × 1016 to 1.31 × 1016 cm−3 by increasing the amount of Eu3+ dopant to 20% in the SnO2 substrate, and this reduction is attributed to the passivation of grain boundaries caused by increased Eu3+ at grain boundaries and interfaces.Grain boundary plays a critical role in determining the charge collection efficiency and stability of PSCs. The passivation of grain boundary can reduce the trap densities of perovskite films to improve the performance of PSCs. Different grain boundary passivation methods are being studied, such as introducing the PbIbI3 PSCs,33 or 2:Eu3+ is expected to be a better ETL for PSCs than the pristine SnO2 film. Therefore, planar‐type PSCs with different SnO2 films as ETL substrates are designed with the structure shown in Figure 3 and Spiro‐OMeTAD are used as the photon absorber layer and hole‐transport layer, respectively. The thicknesses of the perovskites are nearly unchanged by doping 20% Eu3+ into SnO2 film, as shown in the cross‐sectional SEM images of PSCs in Figure S6, Supporting Information.According to the above discussion, SnOJ–V curves of PSCs on various ETL substrates, and the corresponding key parameters, such as the open‐circuit voltage (Voc), the short‐circuit current (Jsc), fill factor (FF), and PCE are all summarized in Table S3, Supporting Information. The maximum PCE of the devices based on the SnO2 ETL substrate is 18.66%, with the corresponding Voc = 1.06 V, Jsc = 22.57 mA cm−2, and FF = 77.77%. It is exciting that the optimal PCE can be increased to 20.14% by changing the SnO2 ETL to SnO2:20% Eu3+ ETL, with corresponding Voc and FF dramatically increased to 1.13 V and 78.76%, respectively. The increased FF are due to the reduced trap density in perovskite film; however, the improved Voc should be attributed to the reduced energy loss in MAPbI3 PSCs.Figure voltage Voc, the sC–V) measurement can be used to investigate the change of built‐in electric field and is carried out to further understand the charge carrier trapping and accumulating behaviors with the incorporation of Eu3+ dopant. Figure C−2–V plots for MAPbI3 perovskite PSCs, and the corresponding values of the built‐in electric fields (Vbi) in the PSCs based on different ETLs are obtained from the Mott–Schottky equation C−2 = (2(Vbi − V))/(A2eɛɛ0N), where C is the capacitance under applied voltage, Vbi is the built‐in potential, V is the applied bias, A is the device area, ɛ is the relative permittivity, ɛ0 is the vacuum permittivity, and N is the free carrier concentration at the edge of the depletion layer. The Vbi for the PSC coated on SnO2:20% Eu3+ ETL is 0.972 V, which is larger than 0.942 V of the control device without europium dopant. The enhanced built‐in potential provides more driving force to separate the photogenerated charge carriers, resulting in an extended depletion region, which suppresses electron‐hole recombination, finally contributing to the increase of Voc.Mott–Schottky analysis based on capacitance–voltage  is in the low‐frequency range, and, in our fabricated PSCs, it increases with increased Eu3+ doping in the SnO2 films. Compared to the control PSCs, the device fabricated on SnO2:20% Eu3+ substrate shows the largest Rrec of 289 Ω, which can effectively inhibit charge recombination at grain boundaries and the interface, because the aggregated Eu3+ at grain boundaries and the interface decrease the amount of negative defects Pb0 and I0.Electrical impedance spectroscopy is carried out to monitor the transfer resistance in PSCs. The Nyquist plots of the PSCs fabricated on different SnOJsc values versus wavelength for the PSCs based on different ETLs. The effect on IPCE of Eu3+ doping in the ETL is divided into two parts: 1) In the UV region of 300–370 nm, the IPCE intensity is enhanced by Eu3+ doping due to the f–f transitions absorption of Eu3+. The absorption of Eu3+ reduces the damage to the perovskite film from UV light, resulting in the obvious increase of the IPCE; 2) The enhancement of IPCE in the region of 370–550 nm is attributed to the increased transmittance of ITO/SnO2:20% Eu3+ substrate. The highest observed IPCE value reaches 92%. Meanwhile, the integrated Jsc increases from 22.22 to 22.33 mA cm−2 by using SnO2:20% Eu3+ film as the ETL substrate, which indicates SnO2:20% Eu3+ is an excellent ETL for application in PSCs. The stabilized power output of the device with SnO2:20% Eu3+ ETL is shown in Figure S10, Supporting Information. While maintaining an external bias near the maximum power output point (0.88 V), the stabilized photocurrent for the PSC with SnO2:20% Eu3+ ETL is 21.37 mA cm−2. The results indicate that SnO2:20% Eu3+ ETL is beneficial to the illumination stability of the MAPbI3 perovskite device.Figure 2:20% Eu3+ substrate exhibits excellent repeatability in contrast to that based on the pristine SnO2 substrate. Figure 2:20% Eu3+ substrate maintains 87% of its initial PCE on the 84th day, but the device coated on SnO2 substrate has decreased to 75% of its initial PCE under the same storage conditions. Their stabilities at higher temperature in N2 atmosphere, even under continuous illumination and higher humidity are both investigated and shown in Figure S11a,b, Supporting Information, respectively. After storing devices in dark with N2 atmosphere at 80 °C for 500 min, the PCE of control device has dropped to 30% of its initial value. But the decrease can be retarded to be very slow by 20% Eu3+ doped in SnO2, thus the device coated on SnO2:20% Eu3+ substrate just decreases to 65% of its initial PCE under the same storage conditions. Even under continuous 100 mW cm−2 illumination and 40–50% humidity at 60 °C for 300 min, the SnO2:20% Eu/Perovskite device can still keep 50% of its initial PCE, but the PCE of SnO2/Perovskite device has drop to 40% of its initial value. The comparison demonstrates that the PSCs coated on SnO2:20% Eu3+ show more excellent stability, which is due to the europium ions can effectively passivate the defects at the grain boundaries and interfaces preventing moisture permeation, further resulting in the improved environmental stability.Stability and repeatability are also very important characteristics for PSCs. The PCE distribution histograms for devices with different ETLs are presented in Figure tability.5032:Eu3+ ETL is developed, and the champion device incorporating it achieves a PCE of 20.14%, showing excellent stability by maintaining 87% of its initial efficiency after storage in ambient atmosphere for 84 days. The excellent performance of the PSCs is attributed to the dual‐passivation effect of europium ions in SnO2. The uniformly distributed europium dopants reduce the trap defects in the SnO2 film, resulting in increased electron mobility of the ETL. The aggregation of europium ions at the interface between the perovskite and SnO2 films is beneficial for improving electron transport through the interface by reducing the charge accumulation at the interface. Moreover, the aggregated europium ions passivate the perovskite by reducing the trap density in the grain boundaries, which is favorable to the Voc and FF of PSCs. Meanwhile, the aggregated europium ions both on the grain boundaries and interface suppress perovskite degradation by preventing moisture permeation. Our dual‐functional method provides a promising direction toward simultaneously optimizing the ETL and perovskite films, and we believe that the present work will facilitate the development of perovskite photovoltaics.This work describes a novel dual‐functional method to simultaneously optimize charge transport characteristics of the perovskite and ETL layers which account for the enhancement of performance of the corresponding PSCs. An effective SnO42·2H2O (98%) was purchased from Macklin. Thioglycolic acid was purchased from Sigma‐Aldrich. EuCl3·6H2O (99.99%) was purchased from CIVI‐CHEM. PbI2 (99.9985%) was purchased from Alfa Aesar. MAI (99.5%) was purchased from Xi'an Polymer Light Technology Corp. Urea, 4‐tert‐butylpyridine (TBP) and bis(trifluoromethane) sulfonamide lithium salt (Li‐TFSI) were purchased from Aladdin. HCl (37 wt%) and chlorobenzene (≥99.0%) were purchased from Sinopharm Chemical Reagent Corporation Co., Ltd. Spiro‐OMeTAD (≥99.0%) was ordered from Youxuan Tech. 4‐Hydroxybutanoic acid lactone (GBL) and dimethyl sulfoxide (DMSO) were ordered from Alfa‐Aesar.SnCl2 layers were prepared by the chemical bath deposition method. Briefly, for the preparation of undoped SnO2 ETL, 0.5 g of urea was dissolved in 40 mL deionized water, and then 10 mL thioglycolic acid and 500 mL HCl were added to the aqueous solution. Finally, SnCl2·2H2O was dissolved in the solution at 0.002 m concentration followed by stirring for 2 min. The clean FTO substrates were immersed in the aqueous solution at 70 °C for 3 h, followed by rinsing in a deionized water sonication bath for 2 min. Then they were dried with flowing air and heat‐treated for 1 h at 180 °C in air. For the preparation of  Eu‐doped SnO2 ETLs, EuCl3⋅6H2O was added directly to the prepared aqueous solution before immersing the cleaned FTO substrates.The FTO‐coated glass (2.5 × 2.5 cm) was cleaned by sequential sonication in acetone, isopropanol, and ethanol for 30 min each time and then dried under air flow and treated by ozone plasma for 6 min. The undoped and Eu‐doped SnO3 perovskite solution (1.4 m) was comprised of MAI and PbI2 in 1 mL of GBL/DMSO = 7:3 (v/v). The solution was stirred at room temperature for 12 h. Then the FTO/ETL substrates were treated by ozone plasma for 6 min. The solution was spin‐coated onto the FTO/ETL substrate by a consecutive two‐step process at 1000 rpm for 10 s and followed by 3000 rpm for 40 s. During the second step, 200 mL of chlorobenzene was dropped onto the substrate. The films were then annealed at 100 °C for 10 min in a nitrogen‐filled glovebox. 90 mg mL−1 spiro‐OMeTAD in 1 mL chlorobenzene with the addition of 36 mL TBP and 22 mL Li‐TFSI solution (520 mg in 1 mL acetonitrile) was spin‐coated onto the perovskite films at 5000 rpm for 40 s. The samples were kept in a desiccator overnight. Finally, 80 nm gold electrodes were deposited on the top of each cell by a thermal evaporator.The MAPbI2 films were characterized by SEM  at an acceleration voltage of 5 kV. XPS measurements were carried out by using a photoelectron spectrometer . SIMS curves were recorded by the time of flight secondary ion mass spectrometry . The J−V performance of the perovskite solar cells was analyzed using a Keithley 2400 Source Meter under ambient conditions at room temperature, and the illumination intensity was 100 mW cm−2 (AM 1.5G Oriel solar simulator) with scan rate 0.2 V s−1. The device area of 0.09 cm2 was defined by a metal aperture to avoid light scattering from the metal electrode into the device during the measurement. TheIPCE was characterized on a QTest Station 2000ADI system , and the light source was a 300 W xenon lamp. The monochromatic light intensity for the IPCE measurement was calibrated with a reference silicon photodiode. The Hall Effect measurements were recorded by the Hall Effect Measurement System (HMS‐3000).XRD spectra were obtained using a D/MAX 2400 diffractometer with Cu Ka radiation (Rigaku). Transmittance spectra were acquired on a PerkinElmer UV‐Lambda 950 instrument. PL  and TRPL spectra  were measured with a PicoQuant FT‐300. Water contact angles were measured using a DataPhysics OCA 20. The surface morphologies of the perovskite films and the SnOThe authors declare no conflict of interest.Supporting InformationClick here for additional data file.


Because the walnut tree is one of the most abundant trees in Iran, it was tried to synthesize Bi2O2CO3 QDNSs using a walnut skin extract. The saturation magnetization for Bi2O2CO3 QDNSs was calculated to be 68.1. Also, the size of products was measured at around 60–80 nm with the Debye–Scherrer equation. Moreover, the morphology, functional groups, and crystallography of the Bi2O2CO3 nanoparticles were investigated using atomic force microscopy, scanning electron microscopy, vibrating-sample magnetometer, and Uv–vis spectroscopy. The results demonstrated that Bi2O2CO3 QDNSs have opto-magnetic properties and they can be suggested as the candidate materials for the sorafenib delivery on the liver tissue. The optical band gap estimated for Bi2O2CO3 QDNSs was found to be red-shift from 3.22 eV. This study suggests the preparation of the Bi2O2CO3 QDNSs based on cellulose as new opto-magnetic materials at different temperatures of 180 °C, 200 °C, 220 °C, and 240 °C for sorafenib delivery as a type of biological therapy drug.This work aimed to prepare solvent-free or green Bi The liver is the hub of the metabolic activity of the body. With the advances in nanopharmaceutical sciences5, more goals have been pursued in service delivery structures to reduce the side effects of different drugs6, as well as improving drug delivery8 in economically feasible ways9. Nanoparticle-based anti-cancer drugs have improved the treatment of various liver diseases and different types of cancer with drug targeting and imaging agents for liver cancer imaging. In particular, magnetic and optic Bi2O2CO3 NPs-based delivery systems provide a good-looking method for localizing sorafenib as clinically important oral tyrosine kinase drugs in the liver using magnetic forces and optical effects. These drugs act at relatively long-range and do not affect most biological tissues. Sorafenib is an inhibitor for the treatment of various cancers10. With the development of new materials or methods, concern about environmental pollution has been doubled due to nanoparticles produced by chemical methods and the production of dangerous side-effects for in vivo preclinical imaging and drug discovery13. Therefore, there is a need for clean, non-toxic, and environmentally friendly green chemistry14. There are different physical and chemical methods for the synthesis of nanostructures in medicine such as chemical remediation16, lithography17, the ultrasonic method18, co-precipitation19, and microwave method20. The disadvantages of this method are the use of chemicals that act as restorative and stabilizing agents21. Nevertheless, these materials cause environmental pollution and these methods have a low production rate in high pressure and high energy during the reaction process22. Solvent-free synthesis as an eco-friendly useful approach23 helps synthesize nano compounds24 without using chemical and dangerous solvents25. The skin green walnut contains 13 phenolic compounds. Among these compounds, joggle is the most frequent and is the main ingredient in the green skin of walnut26. The thermal decomposition method for synthesizing monodispersed metal nanoparticles is one of the best ways to control particle sizes and regular-shaped and well-crystallized nanocrystals27. Today, imaging of living organisms is one of the ways to intercept drugs to treat cancer cells and tumors in the body of living organisms28. Optical drug tracking is performed using various materials that have a high potential in optical properties29. Due to the opto-magnetic properties of nanoparticles, recent studies on the case using the nanostructures as career drugs have been expanded rapidly Table In the past three decades34, nanoparticles exhibit corresponding changes in the emission properties35. The cellulose crystalline structures (CCS) act not only as a suitable substrate for the reductant agent of Bi2O2CO3 QDNSs but also serves as the green capping agent and packaging factor. In this study, we report a new chemical processing without using any solvent (solvent-free method) for the synthesis of Bi2O2CO3 QDNSs. This is a novel and useful opto-magnetic nanomaterial for sorafenib delivery for liver targeting in in-vivo imaging studies. The connection of Bi2O2CO3 QDNSs to sorafenib provides opto-magnetic routing. The synthesized products were characterized by X-ray diffraction (XRD), energy dispersive spectroscopy (EDX), Atomic force microscopy (AFM), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and UV–vis spectroscopy.Because of their unique properties such as large surface to volume ratio and the quantum confinement effect2O2CO3 QDNSs with opto-magnetic properties will enhance drug bioavailability and reduce dosing frequency and prevent hard and impossible treatment therapy. The structures of the suggested Bi2O2CO3/sorafenib formulation are illustrated in Fig. These Bi2O2CO3 nanocrystals in the cellulose base are shown in Fig. a) of the Bi2O2CO3 nanocrystals was obtained from the maximum intensity peak (112) while X-ray density (Dx) was calculated using Eqs. (a is Avogadro number (6.023 × 1023 atoms/mole), M is molar weight, and a is the lattice parameter. Crystallography data show that nanoparticles are likely smaller if the nucleation rate is larger than the crystal growth rate. The results show that the obtained products lack any impurities. Based on the XRD data, the crystalline size and diameter (Dc) of Bi2O2CO3 nanoparticles are calculated about 30–80. These values are estimated using the Scherer equation  throughout the manufacturing process. The XRD patterns 10 < 2θ < 80) of cellulose nanocrystals and Biθ < 80 oftion Eq.  from the2O2CO3 QDNSs is represented in Fig. 2O2CO3 QDNSs, the presence of elements such as C and O elements related to cellulose molecule, and very small quantities of N elements related to the existence of NO3 in precursors. The presence of very small amounts of Ti element can be attributed to unpredictable impurities in the reaction condition and measurement environment.EDX analysis is considered as a non-destructive analytical technique used to identify the percentage of elemental components. A typical EDX spectrum of the Bi2O2CO3 QDNSs treated at 180 °C, 200 °C, 220 °C, and 240 °C, respectively, for 4 h. Based on the SEM images, at 180 °C, Bi2O2CO3 QDNSs show scale-like structures in the presence of the cellulose molecules. As can be seen, with increasing temperature, the density of scale-like structures will increase in the samples. As the temperature gradually rises to 200 °C, the Bi2O2CO3 QDNSs grow on the cellulose surface and a large number of sheet structures can be found in the SEM images. In some areas, there is an overlap between the sheets. Cellulose molecules can play the role of the reductant agent and as a carbon source. Also, they can be responsible for control size and shape capping agent effects in the synthesis process of Bi2O2CO3 QDNSs. Aggregation of nanoparticles occurs due to excessive nucleation at high temperatures. As a result, activation of the surfaces of the nanoparticles causes the product made from Bi2O2CO3 QDNSs to have a larger particle size. It can be observed that Bi2O2CO3 QDNSs synthesized at 220 °C on cellulose-based have more uniform size and shape and these samples have smaller particles size than other samples.Figure 2O2CO3 QDNSs on the cellulose substrate through the thermal decomposition method. In this process, due to the high surface area of the Bi2O2CO3 QDNSs, the particle surfaces aggregated together and bulky structures are achieved when exposed to more heating.As temperature rises from 220 °C to 240 °C, the SEM image indicates an increase in the particle size of the products and generation of bulk Bi2O2CO3 QDNSs and Bi2O2CO3/sorafenib formulation are shown in Fig. −1 and 850 cm−1 correspond to the antisymmetric stretching mode of the CO3 group in Bi2O2CO3 nanostructures36. The absorption band appeared in the area 3300–3400 cm−1 is related to amine (N–H) bands in Bi2O2CO3/sorafenib formulation37. Two strong bands at 675 cm−1 and 1230 cm−1 with different intensities are respectively attributed to stretching of the alkene=C–F and Alkyl-Halide–C–F bonds in sorafenib molecular structures.Fourier transform infrared (FT-IR) spectrum is among the most important, non-destructive, and emerging tools that are widely used to identify organic (and in some cases inorganic) and functional groups in materials. FT-IR of Bi2O2CO3 QDNSs based on the cellulose surface composites (sample c) are shown in Fig. 2O2CO3 nanoparticles are distributed uniformly on the cellulose surface, leading to properties such as opto-magnetic performance. The root-mean-squared roughness (RMS) is an important parameter to introduce the roughness and softness and surface properties of the products. According to the AFM image data, Rrms as the standard deviation factor is determined as follows , TEM images were studied  have uniform size and shape as the cellulose molecules appear in the range of 15–40 nm. The quantitative determination of the solutions, ions, and efficiency conjugated drug compounds were calculated using the Uv–vis spectroscopy.AFM as a non-destructive analysis provides topography of the surface of the samples. AFM images of the Bilows Eq. :5\docume2O2CO3 QDNSs in different temperature conditions and Bi2O2CO3/sorafenib formulation samples are illustrated in Fig. 2O2CO3 nanostructures correspond to the exciton recombination. The emission peaks at 292 nm in Bi2O2CO3 NPs/sorafenib formulation are related to oxygen deficiency and lattice distortion molecular interactions of Bi2O2CO3 nanostructures and sorafenib. Magnetic properties of the nanoparticles’ diamagnetic, paramagnetism, ferromagnets, antiferromagnets, and ferrimagnets materials are measured using the VSM. Figure 2O2CO3/Sorafenib formulation in the air. Using magnetic properties in nanoparticles can create trackable and stable properties in various drugs and cause their interactions with cells or biological proteins, leading to the increased compatibility of drugs. The area within a loop represented in the hysteresis curve indicates magnetic energy loss. The B–H magnetic hysteresis curve for the Bi2O2CO3/sorafenib formulation indicates a very small hysteresis behavior for the samples. It also exhibits small values of coercivity field and remnant magnetization. The saturated magnetization (Bs) values and for Bi2O2CO3 nanoparticles/sorafenib formulation at a magnetic field of 1.5 T was obtained to be 68.1 emu/g. The Bi2O2CO3 nanostructure shows an obvious ferromagnetic behavior, suggesting the presence of the Bi molecule that can exist in the spinel systems.The magnetic properties of the samples were measured with a vibrating sample magnetometer (VSM). The Uv–vis spectroscopies of Bi2O2CO3 nanoparticles/sorafenib in a large number of in rates species, along with phenotypic and gene expression tests. The liver image of mice 2 min after injection and the same rate after 2 months later for the phenotypic investigation are illustrated in Fig. 2O2CO3 QDNSs to glucose structures and tracking these structures in the body. Vertical all-glass Franz-type diffusion cell with an active surface area of 2.37 cm2 and a receptor phase volume of 15 ml was used for the release study of sorafenib from Bi2O2CO3 QDNSs at 37 ± 1 °C. Cellulose acetate dialysis membrane  was used as a barrier between donor and receptor compartments of the diffusion cell. The receptor compartment was filled with normal saline solution (0.9%) and the donor compartment section was filled with 1 ml Bi2O2CO3 nanoparticles/sorafenib. Free drug solutions were used as controls sample and empty Bi2O2CO3 structures were examined as blanks. For this purpose, 1 ml sample was withdrawn at fixed time intervals from the receptor compartment, the same amount of fresh receptor medium was replaced, and the permeated drug concentration was measured. The cumulative release profiles of Bi2O2CO3/sorafenib formulation structures and Bi2O2CO3NPs are presented in Fig. 2O2CO3/sorafenib formulation structures, while the amount of the drug released for sorafenib solution was 2.47%. The reason is that, due to the high surface area of the nanostructures, they absorb more amount drugs on their surface.Initially, no optical properties were observed, but after 2 min, the image shows that the nano substance also contains the drug inside the liver. The evaluation showed that the synthesized material did not have a fatal effect. So, all organs were evaluated phenotypically to ensure that no damage was done to the target tissue and other organs. There was no change in the body tissues, especially the liver tissue. Therefore, it is suggested testing the levels of assurance of designs with different concentrations of Bi2O2CO3 QDNSs can act as an optical and magnetical delivery platform for the tracing sorafenib by magnetic and optical targeting. In the present study, Bi2O2CO3 QDNSs were synthesized and characterized as optical-magnetical carriers for sorafenib delivery in the living organism in the mice. For this purpose, BALB/c male mice were purchased from the Animal Care Center of Research Center, Institute of Neuropharmacology, Kerman University of Medical Sciences, Kerman, Iran. We propose Bi2O2CO3 QDNSs as green chemistry with significant optical and magnetic properties that can be used in the in vivo imaging of the living organism and also in optical density drugs. The TEM image proves that the size of the Bi2O2CO3 QDNSs (sample c) structures are in the range of 15–40 nm. After 240 min, 77.51% and 2.47% sorafenib was released from Bi2O2CO3/sorafenib and sorafenib solution formulation respectively.This study demonstrated that the Bi3)3 was purchased from SRL Company, India, and walnut shells were prepared from gardens around the Sirjan City of Iran. Sorafenib drug type was prepared from Loghman pharmaceutical and hygienic Co. The devices used in this study are as follows: X-ray diffractometer using Ni-filtered Cu-Ka radiation by a Rigaku D-max C III was used for XRD analysis. The EDS analysis was studied using the XL30 Philips microscope. For the morphological properties, SEM devices  were used. TEM  was recorded in the range of 400–4000 cm−1. AFM for surface morphology study was done using an easy scan 2 Advanced Research AFM device. The particle size and particle distribution of the nanoparticles were determined by laser-light scattering . In vivo imaging was obtained using in vivo imaging system F Pro model Kodak manufacturing company in the USA. The UV–visible spectrum of the product was recorded using a Scinco UV–vis scanning spectrometer (ModelS-4100).All the chemical and material reagents used in this study were used with no further purification as they were of pure and analytical grade. The starting reagent Bi3 powder was completely ground in a porcelain mortar. Then, the powder was transferred to a crucible containing black brown precipitations cellulose crystals from the previous step. All these experiments were performed in the same way. The samples were heated in the furnace at different temperament conditions including 180 °C, 200 °C, 220 °C, and 240 °C for 4 h. After the thermal treatment in each step, the system was allowed to cool under argon atmosphere to room temperature naturally and the as-synthesized final precipitations were collected and were characterized by SEM, XRD, Uv–vis, and FT-IR.In the next step, 0.4 g Bi.All the experimental procedures were carried out according to the protocols set for working with animals and for the care and use of laboratory animals at Kerman University of Medical Sciences . Males Balb/c with an approximate weight of about 150–200 g were fed with a standard diet. They were kept under 12:12 h light/dark cycles, at 20 °C, and relative humidity of 25–30% at an animal farm with the local ethics code of 97000588 from the Kerman University of Medical Sciences. The anesthesia was done using Ketamine/xylazine with a ratio of 1:2 followed by immediate injection of BiThis article does not contain any studies with human subjects. The mice  were feeded and raised according to the Institutional Animal Care and Use Committee (IACUC) protocol.


The study included more than 6.2 million individuals. The first sentence of the Results section should have stated that 6 665 429 individuals were identified at birth. In the Supplement, eTable 2 has been replaced with a corrected version. This article has been corrected.1In the Original Investigation titled “Mortality Among Young Adults Born Preterm and Early Term in 4 Nordic Nations,”