The emergence of microbial diseases has become a major concern for humans. In the recent past, we have noticed the emergence and re-emergence of several microbes that include coronaviruses , and others like Zika virus, Nipah virus, Influenza virus, and Ebola virus. These microbes have been noted to spill over from animals into humans. Several such microbes which were previously restricted to wild animals are now becoming responsible for infections in humans and have spread across the borders and resulted in pandemics. It has been more than two years since the discovery of the novel SARS-CoV-2 virus responsible for the coronavirus disease 2019 (COVID-19), and we are still struggling to cope-up with it and live normal lives. Recently, the monkeypox virus, which was confined to West and Central African countries, and caused endemic infections in monkeys and humans was associated with human infections in non-endemic regions like the United States of America (USA) and more than 30 other countries. Therefore, in this editorial, we attempt to put the spotlight on the monkeypox virus that is currently threatening to cause another widespread pandemic. The poxviruses are a large group of deoxyribose nucleic acid (DNA) viruses that include several pox viruses which cause infections in humans and animals. The poxviruses belong to the family of Poxviridaeand are classified into two subfamilies based on their ability to infect vertebrates and non-vertebrates as Chondropoxvirinae and Entomopoxvirinae, respectively. The pox viruses that infect vertebrates including birds, animals, and humans are further classified into various genera that include Orthopoxvirus , Parapoxvirus , Molluscipoxvirus (humans), Yatapoxvirus , Capripoxvirus (goats), Suipoxvirus (pigs), Leporipoxvirus , Avipoxvirus (birds), Crocodylidpoxvirus (crocodiles), and Cervidpoxvirus (deer and cattle). The variola virus , belonging to the Orthopoxvirus group has been noted to frequently cause human infections. After the eradication of the smallpox virus, the vaccinia virus is maintained in the research laboratories and is used as a vaccine strain for immunization against the smallpox virus. Moreover, several pox viruses in animals have the potential to spill over and cause human infections, especially the cowpox virus, and the monkeypox virus .The cowpox viral infection among the milkmaids, and their immunity against severe infection with smallpox virus during the previous smallpox virus pandemics was responsible for the discovery of a vaccine against smallpox in humans by Edward Jenner, who was later called the father of immunization. The monkeypox virus, which belongs to the Poxviridae family, Chordopoxvirinae subfamily, and Orthopoxvirus genus, causes monkeypox disease, which is currently an infrequent zoonotic illness. The classification of the pox viruses and the position of the monkeypox virus are depicted in Figure Monkeypox and smallpox viruses are related closely and monkeypox symptoms are similar to smallpox. The similarity in presenting symptoms of fever and rash between the two viral infections poses an immense significance for effective management. Since the discovery of the monkeypox virus in 1970 in the Democratic Republic of the Congo (DRC), the monkeypox virus and its epidemiology remained unclear. Monkeypox infection spread through contact with infected vesicles and pustular fluids, dressings, and close contact. The contaminated surfaces and material need to be disinfected before further handling. Hand and surroundings hygiene, laundry of clothes, using personal protective equipment, and keeping a safe distance from patients might be useful in breaking the transmission chain [The viruses that generally affected wild animals and were confined to wildlife have been able to successfully crossover into humans. Interestingly, these viral species have adapted extremely well to be able to establish themselves among humans thereby enabling human-to-human transmission. This has been the case with the novel Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), the causative agent of COVID-19. The SARS-CoV-2 was linked to a wet market in Wuhan, China that was a place where different species of birds, seafood, and animals were sold. However, scientists have not been able to identify the exact animal/bird species from which the SARS-CoV-2 could have emerged [Monkeypox is a viral disease that was noted to be restricted to monkeys living in the wild until human cases were identified. This was attributed to the uninhibited encroachment of the wildlife environment by humans, especially in the low-socioeconomic African countries for food and living. However, the virus has now been reported in non-African countries including the United States of America (USA), among others. Before the reports of monkeypox infections among people outside the African nations, the countries that were considered endemic for monkeypox included Cameroon, the Central African Republic, the DRC, and Nigeria .The reason is the illegal transportation of wild, endangered, and exotic animals across the globe. The demand for such animals was due to their flesh, and medical benefits, among others. Moreover, several such animals have also gained demand as pets. Such human behavior could have facilitated the spillovers of several microbes that were restricted to animals into humans. The cause for concern here is the ability of the microbes to undergo genetic variations after the spillovers that help them to adjust to the new/human host. This has been proven by the previous emergence of microbes like the Ebola virus, human immunodeficiency virus (HIV), Zika virus, Nipah virus, severe acute respiratory syndrome coronavirus (SARS-CoV), SARS-CoV-2, and Middle-East respiratory syndrome (MERS) coronavirus, among others. Moreover, several such microbes that crossover from animals to humans and cause serious infections like the SARS-CoV-2 are complex and are not completely understood. Therefore, it is essential to investigate the exact origins of such microbes by extensively screening the wild, domestic, and pet animals throughout the world in a coordinated manner, similar to the one health initiative, that potentially enables scientists to predict any future emergences and the governments to implement control and prevention strategies .Smallpox immunization with the vaccinia virus was found to be effective against monkeypox infections. However, routine immunization against smallpox is no longer recommended after the elimination of smallpox in 1980, and no orthopoxvirus vaccination program has been implemented in almost four decades. The laboratory and clinical confirmation of monkeypox viral infection in humans are complicated by the fact that this virus shares both pathological (eruptive lesions on skin and mucus membrane) and clinical characteristic features with other viruses including the Varicella-Zoster virus (chickenpox virus), and cowpox virus, among others.Monkeypox infection can be diagnosed by isolating monkeypox DNA from a patient's sample and growing it in a viral culture or polymerase chain reaction (PCR). Alternatively, tests that indicate the presence of Orthopoxvirusin a patient specimen, barring patient exposure to another of the same genus, can be sufficient to diagnose, such as electron microscopy visualization, immunohistochemical staining for orthopoxvirus antigens, and serum studies for anti-orthopoxvirus IgM and IgG antibodies. The presence of IgM antibodies implies current or recent evidence of infection or exposure. The presence of IgG antibodies implies previous infection or immunity acquired passively through vaccination.Medical treatment currently is at the clinical trials stage. From previous studies, it was noted that treatment with antiviral therapy consisting of tecovirimat (4-trifluoromethyl phenol derivative) was able to decrease the viral load by reducing the release of intracellular virus from the cell. Brincidofovir and cidofovir were found to inhibit viral DNA polymerase and reduce viral replication cascade . But furThe eradication of the smallpox virus and discontinuation of smallpox vaccination could have contributed to a decline in herd immunity against monkeypox and resulted in the spread of the viral infection. However, the extensive endemic circulation of cowpox, and other vertebrate poxviruses among animals and people living in India and other geographical regions may confer protection by cross-immunity. Therefore, the development of effective vaccination and treatment strategies are to be dealt with in further studies to curb future epidemics. It is also important to perform genomic sequencing of the virus and identify the circulating strains/clades of the virus, their probable origins, host predilections, potential reservoirs, and the risk and severity of infections among humans.


This review highlights the role of TRP channels in cardiac fibroblasts and the possible underlying signaling mechanisms. Changes in the expression or activity of TRPs such as TRPCs, TRPVs, TRPMs, and TRPA channels modulate cardiac fibroblasts and myofibroblasts, especially under pathological conditions. Such TRPs contribute to cardiac fibroblast proliferation and differentiation as well as to disease conditions such as cardiac fibrosis, atrial fibrillation, and fibroblast metal toxicity. Thus, TRP channels in fibroblasts represent potential drug targets in cardiac disease.Cardiac fibroblasts make up a major proportion of non-excitable cells in the heart and contribute to the cardiac structural integrity and maintenance of the extracellular matrix. During myocardial injury, fibroblasts can be activated to trans-differentiate into myofibroblasts, which secrete extracellular matrix components as part of healing, but may also induce cardiac fibrosis and pathological cardiac structural and electrical remodeling. The mechanisms regulating such cellular processes still require clarification, but the identification of transient receptor potential (TRP) channels in cardiac fibroblasts could provide further insights into the fibroblast-related pathophysiology. TRP proteins belong to a diverse superfamily, with subgroups such as the canonical (TRPC), vanilloid (TRPV), melastatin (TRPM), ankyrin (TRPA), polycystin (TRPP), and mucolipin (TRPML). Several TRP proteins form non-selective channels that are permeable to cations like Na Traditionally, the understanding of heart function at the cellular level has focused on contractile cells  as well as pacemaker and conduction cells. Hence, cardiac diseases such as heart failure have been understood as being mainly due to a dysfunction of these cells: loss of contractile function to account for pump failure, and abnormalities of electrical impulse initiation and conduction to account for arrhythmias. With growing interest in conditions such as heart failure with preserved ejection fraction where there is no apparent loss of cardiomyocytes or of conduction cells, there has also been an increase in the attention given to other cardiac cell types and to the extracellular matrix as well as to their alterations under disease conditions . The othvia the opposite actions of proteolytic enzymes such as proteases like metalloproteinases and of anti-proteases  stress. This response consists of increased cell proliferation and ECM protein synthesis. During myocardial injury, cardiac fibroblasts can be triggered to migrate to the site of injury by chemotactic factors and pro-inflammatory cytokines as well as be activated to trans-differentiate into myofibroblasts. The latter are secretory and contractile cells with an even greater capacity for fibrinogenesis and proliferation, resulting in the remodeling of the ECM and the development of fibrosis and the formation of fibrotic scars . Myofibrvia the release of renin and angiotensin-converting enzyme by injured cardiomyocytes, infiltrating macrophages, and other fibroblasts  pathways or Smad-independent non-canonical pathways  and the subsequent translocation of the nuclear factor of activated T cells (NFAT) to the nucleus  ion channels, which are generally Ca2+-permeable. These channels act as biosensors of different physical and chemical stimuli and as mediators of extracellular and intracellular signaling in several types of cells, including myocardial cells . Many TRP channels are present in the heart . In thee review , the ADP2+ influx implicated in pressure overload-induced cardiac interstitial fibrosis in mice  is linked to profibrotic cardiac effects  unfunctional , their role in other tissues, including the myocardium, is less clearly defined. Patients suffering from PKD present with various cardiac abnormalities, indicating that polycystins are also involved in cardiac physiology and pathophysiology. Polycystin 1 (PC1) is present in mouse fibroblasts, where it seems to be localized mainly at the primary cilium detected in these cells, and is implicated in fibroblasts activation . FibrosiGiven the importance of myocardial ischemia as a major cause of morbidity, especially as related to congestive heart failure, here we summarize the role of fibroblast TRPs in the post-ischemic structural and functional changes (cardiac remodeling).. Similarly, TRPP1 was shown to attenuate the fibroblast-myofibroblast differentiation in response to ischemia/reperfusion injury  and iron overload cardiomyopathy , etc. These cardiomyopathies are characterized by metal accumulation into cardiac cells, generally involving cardiomyocytes but it is possible that non-cardiomyocyte cells such as fibroblasts could also be implicated. In general, the entry pathway for the metal is unknown. Although voltage-dependent Caion iron , pharmacin vivo and in cultured cardiac fibroblasts , their expression in other non-myocyte cells like fibroblasts may not have been specified. This could be the case with the highly Cahe heart , and thehe heart . The celhe heart , but dirThe structural complexity of some TRPs may blur the TRP functionality in fibroblasts. Apart from ion channel activity, some TRPs have metabolically active domains that modulate cardiac fibroblasts, like the kinase in TRPM7  and the The multicellular myocardial environment in which cardiac fibroblasts reside also limits the understanding of the role of TRPs in fibroblasts. Depending on the species studied and on the type of fibroblast biomarker and quantification methods used, the fraction of fibroblasts relative to the total number of myocardial cells has been reported to be 64% in rats  or 43–58Several types of TRPs are expressed in cardiac fibroblasts, in which they induce fibroblast proliferation, fibroblast migration, and myofibroblast differentiation as well as fibrinogenesis in response to not only physiological stimuli, but even more so to pathological stimuli, with the potential to produce cardiac fibrosis, arrhythmias, and post-ischemic pathological cardiac remodeling. Other TRPs have antifibrotic effects, whereas a single type of TRP may have both profibrotic and antifibrotic effects, indicating the complexity of the modulation. 2+ and other cations as well as modulate either profibrotic or antifibrotic mediators (The TRPs in fibroblasts act as sensors of various stimuli and as pathways of entry of Caediators . Nonethe


Compassion is a warm response of care and concern for those who are suffering, which drives individuals to devote their resources for the sake of others. A prominent evolutionary framework grounds compassion in the neurobiology of the caregiving system - the inborn motivation to support close others in times of need. The current review paper investigates the neurobiological mechanisms of compassion, and in particular, the neuropeptide oxytocin which is known to play a significant role in caregiving. Integrating the state-of-the-art literature on oxytocin with the current understanding of compassion, we suggest that oxytocin regulates the necessary precursor of compassion, i.e., the saliency of pain and distress cues. In according to this view, social cues are more likely to be noticed and responded to in an oxytocin-enriched environment. This framework focuses on the saliency processes in the context of social suffering. It sheds light on two central aspects of compassion. First, it highlights the less investigated initial stages of compassion, i.e. sensitivity and attentiveness to pain and distress. Second, it opens the door to the vast variability of social responses when facing suffering others, by demonstrating that emotions, motivations and behaviors elicited by such sensitivity to pain are crucially dependent on context and personality.Compassion is a warm response of care and concern for those who are suffering, which drives individuals to devote their resources for the sake of others. A prominent neuroevolutionary framework grounds compassion in the neurobiology of the mammalian caregiving system. Accordingly, it has been suggested that the oxytocinergic system, which plays a central role in parental caregiving and bonding, provides the neurobiological foundation for compassion towards strangers. Yet, the specific role of oxytocin in compassion is far from clear. The current paper aims to target this gap and offer a theoretical framework that integrates the state-of-the-art literature on oxytocin with research on compassion. We suggest that oxytocin mediates compassion by enhancing the saliency of cues of pain and distress and discuss the plausible underlying neurobiological substrates. We further demonstrate how the proposed framework can account for individual differences in compassion, focusing on the effects of attachment on caregiving and support. The proposed framework integrates the current scientific understanding of oxytocin function with compassion-related processes. It thus highlights the largely ignored attentional processes in compassion and taps into the vast variability of responses in social contexts involving pain and suffering. Compassion is a warm response of care and willingness to alleviate suffering, which may have evolved in humans to increase survival . Indeed,A crucial question in compassion research concerns the neurobiological mechanisms driving these other-oriented motivations, which can arise despite significant self-costs. Multiple voices in the literature have suggested that the mammalian caregiving system, evolutionarily designed to ensure caring for offspring, plays a pivotal role in the compassionate motivation to attend to and care for less fortunate members of a group ,11,12,13These theoretical claims, which assign a pivotal role to oxytocin in the context of compassion, are supported by substantial empirical findings linking oxytocin with various indexes of care and empathy. For instance, a comprehensive series of studies employing acute intranasal oxytocin treatment have shown that exogenous oxytocin significantly increased emotional empathy  and compassion  towards pictorial characters in emotionally charged situations ,18,19,20Despite this body of evidence and common theoretical claims, the specific functional role of oxytocin in compassion remains surprisingly unclear. A widely accepted framework suggests that oxytocin exerts its effects by optimally orchestrating reward- and stress-related systems and their interconnections ,34,35,36In the current work, we aim to delineate the potential role of oxytocin in eliciting compassionate responses towards distressed strangers while building upon the tremendously rich and evolving science regarding oxytocin. We first present the widely agreed-upon contemporary framework of oxytocin’s function, which highlights its pivotal role in shaping the saliency of social cues in a context-dependent manner . We thenThe researchers increasingly acknowledge that the effects of oxytocin are not uniform and are more complex than previously believed . For insOverall, the SSH has received substantial empirical support. Central to the current study, research on social attention has consistently demonstrated that oxytocin increases attention towards social but not non-social stimuli in humans and monkeys ,58,59,60To summarize, previous research on social attention and recognition of social-emotional signals has shown that intranasal oxytocin enhanced attention to social stimuli and affected the saliency of critical features of these stimuli. This impressive body of research highlights saliency signaling as a central role of oxytocin, which may or may not lead to pro-sociality.While there are many definitions of compassion, all of them seem to agree that compassion encapsulates attentiveness and sensitivity to social signals of distress ,72. SignIntegrating the SSH with the significance of distress cues for caring, we suggest that oxytocin may modulate the saliency of distress cues which, in turn, can significantly shape compassionate responses. A recent pharmacological eye-tracking study showed that oxytocin administration enhanced visual attention to emotionally salient regions, i.e., faces. Notably, increased attention to the face region in negative scenes was correlated with increased empathy rates for those pictured . Other sTo summarize, we suggest that oxytocin modulates the attentional, perceptual, and motivational aspects of distress processing. Accordingly, oxytocin is not a mechanism of compassion per se, in the sense that increases in oxytocin causally lead to increases in compassion. Instead, oxytocin regulates a key saliency process that has the potential to impact compassion for others, as well as a variety of other social behaviors, depending on the context and individual differences.The mesolimbic dopaminergic reward system is the brain’s central motivation system. It signals the significance of stimuli, assigns motivational value, and selects appropriate action, such as approach or avoidance. The dopaminergic reward circuitry is believed to encode "incentive salience," i.e., the attention-grabbing and motivational features of rewards and their learned cues ,86. RemaIn line with this model, neuroimaging research has demonstrated that activation of the brain’s reward circuitry is directly linked to compassionate responses to suffering ,97, as wTo summarize, several converging lines of evidence have suggested that neural modulation via oxytocin of the dopaminergic reward-related neural circuits may play a pivotal role in driving compassionate responses to suffering. Centrally, this neurobiological model combines the attentional-perceptual aspects of the SSH described in the previous section and the pro-social motivation aspects of earlier models of oxytocin ,15,36 byHumans are not routinely compassionate when facing others in distress. The willingness and motivation to care for others are fragile and highly dependent on individual characteristics, available resources, and social context ,78. ReseThe diversity of social behaviors in empathic contexts resonates well with the SSH, which suggests that the effects of oxytocin-driven saliency of social cues vary as a function of context as well as individual differences of the perceivers ,48,104. Combining the SSH framework with evidence of individual differences in compassion ,106, we In the above section, we showed how oxytocin-driven processes might underlie the variability of behaviors in social contexts, increasing care and compassion if certain conditions are met but inhibiting it if other conditions occur. In the next section, we demonstrate how the saliency processes interact with the vital personality characteristic in the context of compassion and care, i.e., attachment patterns. One of the most comprehensive frameworks for individual differences in caring and compassion is the attachment theory, which concerns the effects of early life close relationships on patterns of thought and behavior in subsequent relationships ,112,113.Significantly, attachment security does not simply boost the propensity for social engagement. In resonance with the SSH, attachment security facilitates sensitivity and attunement to social cues, potentially via the modulation of social signals saliency through the oxytocin pathways ,36,120. Seminal studies on the provision of support in romantic relationships have provided an exquisite example of how the saliency of distress cues on behalf of the support seeker can elicit different experiences and behaviors from the support provider as a function of their attachment patterns . For parOverall, these studies demonstrate that individuals with secure attachment are more sensitive to the needs of others and are better able to modulate their attentional, emotional, and motivational processes in a way contingent on their partners’ expressions of distress . In contIt is plausible that the above-described effects of attachment on compassion are mediated via oxytocinergic pathways as attachment and oxytocin exhibit intricate interactions. Both human and rodent studies have demonstrated that oxytocin plays a central role in forming and manifesting attachment and caregiving systems ,130,131.En masse, this evidence suggests that attachment security is linked with basal oxytocin levels and the release of oxytocin in response to social cues. Accordingly, attenuated saliency of social distress cues may mediate the the disrupted support provision in individuals with attachment insecurities. In support, insecurely attached individuals were shown to benefit more from the intranasal administration of oxytocin in social contexts involving trust, intimacy, and cooperation ,136,137.Introducing saliency processes into the functional model of oxytocin has allowed the integration of vast variability of oxytocin effects under one theoretical umbrella. This review has aimed to extend this explanatory model to include the context of compassion. The resulting integrative framework offers two straightforward advances for understanding compassion mechanisms. First, it provides a neurobiological account of the critical component of compassion, namely, sensitivity to cues of suffering . Second,The saliency model of oxytocin highlights the less investigated attentional processes in compassion. While an essential part of compassion is to be "attentive to the distress and needs of another" , little Integration of oxytocin-driven saliency aspects in compassion-related processes highlights the variable response repertoire in social distress. Caring for others is a costly behavior and, therefore, is generally more likely to be focused on kin and allies . Thus, cThe effects of context and personality on compassion, presented in the previous section, lead to an intriguing conclusion: the dependency of compassion on the neurobiology of mammalian caregiving grounds the human pro-social system in habitual responses that reactivate existing personality patterns and learned associations when facing suffering others . Therefo


Discoid lupus erythematosus and oral lichen planus are chronic systemic immune system-mediated diseases with unclear etiology and pathogenesis. The oral mucosa is the common primary site of pathogenesis in both, whereby innate and adaptive immunity and inflammation play crucial roles. The clinical manifestations of discoid lupus erythematosus on the oral mucosa are very similar to those of oral lichen planus; therefore, its oral lesion is classified under oral lichenoid lesions. In practice, the differential diagnosis of discoid lupus erythematosus and oral lichen planus has always relied on the clinical manifestations, with histopathological examination as an auxiliary diagnostic tool. However, the close resemblance of the clinical manifestations and histopathology proves challenging for accurate differential diagnosis and further treatment. In most cases, dentists and pathologists fail to distinguish between the conditions during the early stages of the lesions. It should be noted that both are considered to be precancerous conditions, highlighting the significance of early diagnosis and treatment. In the context of unknown etiology and pathogenesis, we suggest a serological and genetic diagnostic method based on TNF-α and IL-10. These are the two most common cytokines produced by the innate and adaptive immune systems and they play a fundamental role in maintaining immune homeostasis and modulating inflammation. The prominent variability in their expression levels and gene polymorphism typing in different lesions compensates for the low specificity of current conventional diagnostic protocols. This new diagnostic scheme, starting from the immunity and inflammation of the oral mucosa, enables simultaneous comparison of discoid lupus erythematosus and oral lichen planus. With relevant supportive evidence, this information can enhance physicians’ understanding of the two diseases, contribute to precision medicine, and aid in prevention of precancerous conditions. Lupus erythematosus is a general term for a group of chronic, recurrent autoimmune diseases that manifests in two main forms: systemic lupus erythematosus (SLE), which involves multiple organs, and cutaneous lupus erythematosus (CLE), which is limited to the skin and mucosae . Among CDespite the unclear etiology, it is known that DLE and OLP are regulated by the immune system. Multiple immune factors participate in the pathogenesis of DLE and OLP. Therefore, to address this clinical dilemma, it is necessary to identify immune factors that are strongly correlated with DLE and OLP, and to achieve a definite diagnosis by detecting differences among them. During our investigation, we found that a series of prospective studies and reviews highlight genotypes and expression levels of IL10 and TNF-alpha as characteristic and promising immunologic differentiators. It is expected that more accurate diagnosis will facilitate more precise and timely treatment.OLP is a common chronic inflammatory disease that manifests with oral mucosal and cutaneous lesions. It is characterized by lacelike white stripes on the oral mucosa with an abnormality of keratinization. The distribution of the lesions is primarily bilateral and symmetrical, particularly in the buccal mucosa. The disease can be classified as reticular, plaque-like, atrophic, bullous, erosive, and popular types according to their morphological characteristics. During the clinical course of the disease, the different types of lesions can transform into each other. After remission of the disease, pigmentation may remain on the mucosa. The pathological hallmarks are liquefied degeneration of the basal lamina and dense lymphocytic infiltration of the lamina propria with a predominance of T cells. OLLs are a heterogeneous group of diseases with clinical manifestations and histopathology similar to OLP, also known as oral lichenoid reactions (OLRs). In 2006, at the World Workshop in Oral Medicine IV, OLLs were separated into oral lichenoid contact lesions (OLCL) caused by contact with dental restorative materials, oral lichenoid drug reactions (OLDRs) caused by certain systemic drugs, and oral lichenoid lesions of graft-vs.-host disease (GVHD) . The WHOProgress regarding the development of OLL classifications has been achieved by the inclusion of more subtypes and the addition of OLL definitions. At present, DLE is classified as a type of OLL because of similarities in clinical and histopathological manifestations, cell kinetics, immune alterations, treatment, and prognosis. First, from an epidemiological perspective, young and middle-aged women are susceptible to both disorders. In terms of clinical manifestations, oral lesions of DLE occur on the buccal mucosa, vermilion, gingiva, dorsal tongue, ventral tongue and palate; whereas for OLP, any part of the oral mucosa could be affected, with the buccal mucosa being the most common . Oral leDespite consideration of the clinical details, pathologists can only conservatively report the lesion as either OLP or OLL . Lu et aImmunological methods have been widely used as an adjunctive diagnostic tool for OLP and DLE. Unlike pemphigus, pemphigoid, and other oral mucosal autoimmune diseases, DLE and OLP lack specific pathological manifestations. The immunopathological diagnosis mainly relies on observing the distribution and types of various immune factors. In an earlier comparative study , it was Heat shock proteins (HSPs) have been implicated as antigenic stimuli of autoimmune diseases, also known as “stress proteins” and “molecular chaperones”. The two subtypes of HSPs, HSP60 and HSP70, are highly competent for T-cell activation, and histological studies demonstrate that OLP is a T-cell mediated disease , 24. MeaTNF-α belongs to the TNF/TNFR cytokine superfamily, and is one of the most important pro-inflammatory cytokines and potent immunomodulators that regulates a wide range of immune-related activities, including inflammation, innate and adaptive immune responses, and autoimmunity . TNF-α iin vitro lymphocyte stimulation  (rs18000896), 819 (C/T) (rs1800871) and 592 (C/A) (rs1800872) generate three haplotypes , which are associated with the transcription rate of IL-10 and variability in IL-10 production , 58. IL-in vitro analysis of IL-10 mRNA and expression using 35S-labelled oligonucleotide probes and polymerase chain reaction showed that cells capable of generating IL-10 mRNA were present in the original lesions of OLP , and then the frequency of their alleles can be determined qualitatively by typing gene polymorphisms using a polymerase chain reaction (PCR) with sequence specific primers, i.e., allele A of TNF-α (-308 A>G) and allele G of IL -10 (-1082 A>G). This novel diagnostic scheme is expected to facilitate the screening of DLE from the previous histopathological classification of OLLs or, more directly, to confirm suspected cases as DLE or OLP. Therefore, the protocol for the admission of patients is described as below: the initial step is the exclusion of other definable diseases or impairments based on evidence from the initial clinical examination, followed by the above recommended methods for ancillary diagnosis. Given the invasive nature of surgical biopsy and the potentially malignant nature of OLP and DLE, the lesional biopsy is the last diagnostic option to be considered  (Grant Nos. 82002877) and Young Talent Project of Sichuan Provincial People’s Hospital (No. 2016QN15) contributed to the design of the study, the collection, analysis, and interpretation of data, and writing the manuscript.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


With the growing burden of cancer, parallel advancements in anticancer nanotechnological solutions have been witnessed. Among the different types of cancers, breast cancer accounts for approximately 25% and leads to 15% of deaths. Nanomedicine and its allied fields of material science have revolutionized the science of medicine in the 21st century. Novel treatments have paved the way for improved drug delivery systems that have better efficacy and reduced adverse effects. A variety of nanoformulations using lipids, polymers, inorganic, and peptide-based nanomedicines with various functionalities are being synthesized. Thus, elaborate knowledge of these intelligent nanomedicines for highly promising drug delivery systems is of prime importance. Polymeric micelles (PMs) are generally easy to prepare with good solubilization properties; hence, they appear to be an attractive alternative over the other nanosystems. Although an overall perspective of PM systems has been presented in recent reviews, a brief discussion has been provided on PMs for breast cancer. This review provides a discussion of the state-of-the-art PMs together with the most recent advances in this field. Furthermore, special emphasis is placed on regulatory guidelines, clinical translation potential, and future aspects of the use of PMs in breast cancer treatment. The recent developments in micelle formulations look promising, with regulatory guidelines that are now more clearly defined; hence, we anticipate early clinical translation in the near future. Breast cancer is one of the most frequently diagnosed cancers causing death among women, thereby posing a severe global burden . Among tMolecular subtypes of breast cancer include human epidermal growth factor receptor-2 (HER-2), triple-negative breast cancer (TNBC), estrogen (ER)/progesterone receptor (PR)-positive or -negative molecular subtypes, and luminal A and luminal B  ER/PR-poNormally, the adoption of any regime is based on the condition of the patient and the stage of the disease. The standard approach to treat breast cancer is to use cytotoxic chemotherapeutics before surgery, as it is a less invasive technology, or to reduce the extent of surgery, which is called neoadjuvant therapy ,6. OtherNanotherapeutics are part of a powerful strategy employed to deliver hydrophobic drugs to overcome certain challenges and improve drug efficacy. Nanomedicine is a broadly applied term for various types of systems, such as liposomes , polymerThe most commonly employed hydrophilic part is polyethylene glycol (PEG), along with other emerging polymers, such as poly(vinylpyrrolidone) and poly(trimethylene carbonate) . The hyd−1 ..113].Majorly developed new nanotechnology fails the criteria for efficacy due to the insufficient amount of studies conducted to meet basic criteria for clinical trials, i.e., ease of fabrication, reproducibility, and long-term stability of the nanosystems. Hence, many of the reported formulations for cancer therapy have not advanced to an appropriate level . PresentA properly designed nanomaterial database with up-to-date information should be designed to mine necessary information and assign nanostructure-based annotations. This knowledge helps facilitate the development of nanoparticles with definitive or near-predicted properties under biological conditions. With such a vision, the Nanoinformatics Roadmap 2030 was undertaken by the USA and the European Union, including a few other countries, in 2018 . This inThe quality target product profile is derived by considering aspects such as micelle formulation, sterility, and pharmaceutical quality. The targets for the attributes were fixed based on the product label as desired by the respective agencies (examples are provided in The unit operations and the process parameters in the manufacturing process of micelle injections are very important and dependent on the manufacturing process. It is essential to develop scalable and controllable methods to achieve consistent results in the production process. Example unit operations and process parameters are provided for PMs in PMs represent a major contribution to the nanomedicine field, especially in anticancer therapy. PMs are next-generation drug delivery systems in the treatment of breast cancer and TNBC for delivering target-specific, poorly water-soluble drugs. PMs are known to enhance the loading efficiency of drugs and are easy to prepare in comparison to other nanoformulations. However, PM clinical translation is hindered primarily by nonpredictable stability in biological conditions and a lack of a cost-effective reproducible production strategy. Hence, the principal focus lies in overcoming these drawbacks. Thus, understating the relationship between the physicochemical properties and in vivo behavior of PM is an important area of investigation. This can be supported through extensive studies to determine the stability of formulation in various conditions such as in vitro and in vivo conditions such as oral administration, blood, saliva, etc. Furthermore, scalability could be improved by adopting technologies such as microfluidic technology .Moreover, the clinical translation of nanomedicines can be improved with the help of recent advances in science and technology. The emergence of machine learning and artificial intelligence has provided novel techniques for toxicity testing and can be employed for predicting nanoformulation toxicity. Such technology can be used to predict the biological response, pharmacokinetics, and behavior in the target organ . In addi


Streptococcus pneumoniae (pneumococcus) with the alveolar epithelium. Invasive pneumococcal disease is an important health problem that may occur as a result of the spread of pneumococcus from the lower respiratory tract to sterile sites. We show here an efficient experimental approach to model the main events of the pneumococcal infection that occur in the human lung, exploring bacterial adherence to the epithelium and internalization and triggering an innate response that includes the interaction with surfactant and the expression of representative cytokines and chemokines. Thus, this model, based on human minilungs, can be used to study pneumococcal virulence factors and the pathogenesis of different serotypes, and it will allow therapeutic interventions in a reliable human context.The new generation of organoids derived from human pluripotent stem cells holds a promising strategy for modeling host-bacteria interaction studies. Organoids recapitulate the composition, diversity of cell types, and, to some extent, the functional features of the native organ. We generated lung bud organoids derived from human embryonic stem cells to study the interaction of IMPORTANCEStreptococcus pneumoniae is responsible for high morbidity and mortalities rates worldwide, affecting mainly children and adults older than 65 years. Pneumococcus is also the most common etiologic agent of bacterial pneumonia and nonepidemic meningitis, and it is a frequent cause of bacterial sepsis. Although the introduction of pneumococcal vaccines has decreased the burden of pneumococcal disease, the rise of antibiotic-resistant strains and nonvaccine types by serotype replacement is worrisome. To study the biology of pneumococcus and to establish a reliable human model for pneumococcal pathogenesis, we generated human minilungs from embryonic stem cells. The results show that these organoids can be used to model some events occurring during the interaction of pneumococcus with the lung, such as adherence, internalization, and the initial alveolar innate response. This model also represents a great alternative for studying virulence factors involved in pneumonia, drug screening, and other therapeutic interventions. Streptococcus pneumoniae (pneumococcus) is the leading cause of severe bacterial pneumonia, with high morbidity and fatality rates worldwide. Lower-respiratory infections were responsible for over 2.74 million deaths in 2015 and the third major cause of mortality worldwide in children under 5 years of age, with S. pneumoniae being the leading cause of these infections  cells (responsible for gas exchange and surfactant production) or their responses during the initial infection, including the early phases of acute pneumonia. This is partially due to the lack of reliable cell models and the difficulty of extracting, establishing, and maintaining primary ATI and ATII cells in culture. In the alveoli, ATII cells represent the preferred target for pneumococcal adherence and cell damage . 16–t0, there were multiple bacteria in the lumen , CFUs on the order of 6 × 106 were found in the cell extracts . To evaluate the host-pathogen interactions, we used bacterial mutants in LytA, PspC, and the double mutant in LytA/PspC, because they are important virulence factors involved in pathogenesis  showed reduced bacterial levels compared to the wild-type strains. These results demonstrate that LytA and PspC, to a greater extent, are surface-exposed proteins involved in the interaction of S. pneumoniae with lung epithelial cells . Taken together, these results suggest that the fast decay of bacterial viability observed might be due to the interaction with surfactant that could be contributing to the control of bacterial levels. It has been reported that different surfactant proteins, such as SFTPA and SFTPB, have antimicrobial activity by affecting the depolarization and permeabilization of the bacterial membrane and the induction of toroidal pores , IL-8, TNF-α, CXCL5, and CCL20 (MIP3) because they are important components of the host immune response involved in the recognition of and inflammatory response to invading pathogens such as S. pneumoniae  to build lung bud organoids (LBOs) that develop branching airway and early alveolar structures embedded in Matrigel sandwiches. The use of the hESC line AND-2 and the experimental procedures of this study were approved by the ISCIII Ethics Committee (reference no. CEI PI 10_2015-v2) and the National Committee of Guarantees for the Use and Donation of Human Cells and Tissues (reference no. 345 288 1 and 436 351 1). Lung organoids like those generated here have numerous advantages over cell lines or simple primary cultures, as they offer an unlimited availability of primary cells and can emulate structural and functional features of the original organ. The generation of optimal lung organoids relies primarily on the selection of good hESCs showing adequate morphology when growing, along with inactivated feeder cells (inactivated mouse embryo fibroblasts [iMEFs]). hESCs are picked up and passaged to new plates with iMEFs to accumulate material for subsequent differentiation to the lung lineage. extracts . A fast extracts . The bacextracts . The bacextracts . Similarogenesis , 23. Oural pores , 24. Theal pores . Upon inal pores , 26. Thenfection . In addiS. pneumoniae with the alveolar epithelium, including the host immune response. Below, we summarize the potential of the model presented here in terms of human material availability, time, and relevance to pneumococcal biology.These minilungs are human primary cells organized into 3D structures mimicking the structure and function of the native organ.The system shows an unlimited and rapid availability of precious primary human material. The hESCs or lung lineage progenitors can be expanded to an unlimited extent to get enough material for the differentiation process.Infective bacteria can be delivered directly to the lumen by microinjection to mimic alveolus exposure to exogenous agents.This model has enormous potential for studying the adherence of bacteria to the eukaryotic cell during the early stages and the influence of bacterial virulence factors. This potential includes the possibility of therapeutic interventions: developing antiadhesive strategies to block transmission and colonization.This model will allow the establishment of specific individual organoids, organoid biobanks, and high-throughput analyses. The application of this protocol to induced PSCs (iPSCs), for instance, will allow the development of individual-specific minilungs to study pneumococcal interactions with the alveolar epithelium, alveolar innate responses, and the interaction of pneumococcus with chronic diseases such as chronic obstructive pulmonary disease (COPD). In addition, the use of human PSCs (hPSCs) may serve to set up biobanks with minilungs from different individuals for modeling targeted drug treatments.Overall, our study demonstrates the suitability of hESC-derived lung organoids for modeling early interactions of Please contact the corresponding author for data requests.


The obesity epidemic has serious implications for women of reproductive age; its rising incidence is associated not just with health implications for the mother but also has transgenerational ramifications for the offspring. Increased incidence of diabetes, cardiovascular disease, obesity, and kidney disease are seen in both the mothers and the offspring. Animal models, such as rodent studies, are fundamental to studying maternal obesity and its impact on maternal and offspring health, as human studies lack rigorous controlled experimental design. Furthermore, the short and prolific reproductive potential of rodents enables examination across multiple generations and facilitates the exploration of interventional strategies to mitigate the impact of maternal obesity, both before and during pregnancy. Given that obesity is a major public health concern, it is important to obtain a greater understanding of its pathophysiology and interaction with reproductive health, placental physiology, and foetal development. This narrative review focuses on the known effects of maternal obesity on the mother and the offspring, and the benefits of interventional strategies, including dietary intervention, before or during pregnancy on maternal and foetal outcomes. It further examines the contribution of rodent models of maternal obesity to elucidating pathophysiological pathways of disease development, as well as methods to reduce the impact of obesity on the mothers and the developing foetus. The translation of these findings into the human experience will also be discussed.  The global incidence of obesity continues to rise at alarming rates. Concerningly, the incidence of women of childbearing age with obesity is escalating, leading to risks for both the mother and the child . ObesityAnimal models of maternal obesity are highly beneficial in probing the effects of maternal obesity on maternal and foetal outcomes, as well as interrogating the effectiveness of weight modulation during and prior to pregnancy. Animal studies have the advantage of controlled experimental design, allowing a specific maternal perturbation to be induced to determine its influence on maternal and perinatal outcomes while minimising the confounding effects of genetic and postnatal environmental influences. Further, rodent strains are highly susceptible to weight gain when fed a high-fat diet (HFD), and they can manifest features of the metabolic syndrome, namely obesity, insulin resistance, diabetes, and hepatic steatosis . This article reviews the current evidence using rodent models of obesity and weight reduction before or during pregnancy on maternal and neonatal outcomes. Our review will highlight current evidence gaps and generate meaningful and translatable avenues for research in the area of interventional strategies for maternal obesity. Rodent studies have contributed to the growing body of evidence that exposure to a maternal obesogenic environment has deleterious effects on maternal health. Maternal obesity is associated with reduced fertility ,9 and inHigh saturated fatty acid (SFA) intake in maternal mice has been shown to be deleterious for total cholesterol and LDL-cholesterol levels , which iAbnormal placentation has been observed in rodent models of obesity. Placenta from HFD-fed obese mouse dams show impaired placental development and vascularization, which may mediate foetal growth changes through the reduced transfer of nutrients across the placenta . ChronicSimilar to the findings in rodent studies, the pathophysiologic changes associated with obesity in human pregnancy include the upregulation of systemic inflammation, hormonal aberrations, and immunologic dysregulation ,54,55,56Maternal obesity has effects on human placental physiology. The upregulation of inflammation occurs in the placentas of obese women, and increasing inflammatory markers are detected in the foetus . IncreasOverwhelmingly, rodent studies show foetal overgrowth as a major consequence of maternal obesity ,45,64,65In comparison to the known mechanisms and effects of maternal obesity on perinatal complications for the mother and the neonate, the developmental influences of maternal obesity on the long-term health of the offspring are less well established, especially in human studies. Rodent studies have been helpful in establishing the growing body of evidence that a maternal obesogenic environment in pregnancy is a determinant of metabolic dysregulation in the offspring that lasts a lifetime. A large accumulating body of evidence overwhelmingly supports the concept that maternal obesity programs the development of metabolic disease and obesity in the offspring. Offspring exposed to maternal obesity, fed a hypercaloric diet, show a greater propensity to non-alcoholic liver disease . Adult fOur research team has previously shown that the offspring of obese dams have sustained upregulation of oxidative stress pathways in the kidneys of male adult offspring ,79. The Maternal obesity affects offspring subfertility. In the male offspring of obese dams, sperm quality and function are impaired, with deficiencies in sperm mitochondrial function and a higher number of abnormal metaphase and greater reactive oxygen species . SimilarThe programming effects of maternal obesity on the offspring are potentiated by postnatal diet-induced obesity . Our preThe impact of developmental programming due to maternal obesity differs by sex of the offspring in rodent models. Male offspring, compared to female offspring, show greater body weight, retroperitoneal fat mass, liver mass, plasma leptin levels, and impaired glucose tolerance ,88. FurtDiscerning the impact of genetic disposition, postnatal environment, and foetal programming on offspring outcomes is problematic in human studies. Population-level data suggest that the adult offspring of mothers with obesity have a greater risk of premature death, mainly driven by cardiovascular disease . Higher Interventional strategies for obesity during pregnancy have the potential to influence health outcomes for both the mother and the offspring. However, few studies have investigated the effect of interventional strategies for weight modulation during pregnancy in rodent models. One study utilised a modified fatty acid composition diet enriched with medium-chain fatty acids and decreased polyunsaturated fats to demonstrate reduced maternal body weight, adipocyte size, and hepatic fat accumulation compared to unmodified HFD fed mice. Moreover, there was a trend toward lower fasting glucose, insulin, and leptin concentrations in the mothers . Fish oiIncreased physical activity in the form of voluntary exercise during pregnancy improves maternal insulin and glucose sensitivity, though this did not translate to reduced body weight, duration of gestation, litter size, or neonatal weight . ImportaStudies on pregnant women intending to reduce obesity-related adverse events by limiting gestational weight gain have shown only modest effects. The LIMIT trial was a large study of supervised lifestyle modification in pregnancy involving 2152 women and 2142 liveborn infants. Neither improved maternal outcomes of pregnancy nor reduced neonatal morbidity, including large for gestational age, were seen . DisappoThere are few studies that have investigated the benefits of pre-pregnancy weight modulation on maternal and offspring health in rodent models of maternal obesity. These studies include interventional strategies with diet modification, dietary supplements, pharmacological agents, and surgery.Switching the rodent diet from HFD to chow in the preconception period results in progressive improvements in insulin sensitivity, glucose tolerance, and serum insulin over the course of 4 weeks of diet change. Further, cholesterol levels also improved ,112. TheAn interesting study that examined the impact of maternal exercise on perinatal outcomes in mice found that exercise throughout the pregestational and gestational periods, rather than pregnancy alone, was most efficacious for improving glucose tolerance and peripheral insulin sensitivity . Such efPre-pregnancy pharmacological interventions are limited. Dennison et al. investigated preconception use of probiotics alone or in combination with a dipeptidyl peptidase 4 inhibitor (DPP-4 i), sitagliptin, with or without probiotics, and found reduced maternal body weight, improved insulin sensitization and outcomes of pregnancy in obese mice but not improved fertility . Our recent study showed that the use of the glucose-like peptide-1 (GLP-1) agonist, liraglutide, in the preconception period is an effective interventional strategy to reduce maternal body weight, improve maternal glucose tolerance and lipid metabolism, and fertility rates were improved in obese mice treated with pre-pregnancy liraglutide . InteresThe use of preconception bariatric surgery to facilitate rapid and significant weight loss has been examined in HFD-fed rodent models of maternal obesity. A study using vertical sleeve gastrectomy, involving an 80% excision of the stomach, resulted in significantly reduced caloric intake, adiposity, circulating lipids, and improved glucose tolerance in the dams and their reproductive cycle normalized inferring better fertility outcomes. Offspring, however, showed evidence of growth restriction, with greater levels of glucose intolerance and increased adiposity than the offspring of lean mothers or obese mothers who underwent sham surgery . SimilarOverall, preconception diet, exercise and pharmacotherapy for weight loss show promising signs of benefits for maternal and neonatal health; however, significant weight loss with surgical intervention appears to be too drastic with potentially adverse outcomes for the offspring. Importantly, no studies to date have examined the impact of pre-pregnancy intervention for maternal obesity on the long-term health of the offspring.The benefits of preconception weight loss have been explored in few human studies. Hypocaloric diets in the preconception period can induce weight loss and, therefore, subsequently improve fertility . The PreBariatric surgery before pregnancy is an effective approach for achieving pre-pregnancy weight loss and improved fertility with a lower incidence of miscarriage or congenital malformation in women with severe obesity. However, weight loss surgery can lead to vitamin deficiencies, preterm delivery, and small-for-gestational-age outcomes if pregnancy ensues within 12 months of surgery ,126. As The research to date has uncovered many avenues for further investigation. There is still much to uncover about the mechanisms underpinning foetal programming. The role of oxidative stress and meta-inflammation (the combination of low-grade chronic inflammation and metabolic dysfunction observed in diabetes and obesity ) in offsThe possible avenues for intervention are numerous and worthy of further investigation. Either pre- or interpregnancy weight-loss interventions are still not demonstrably effective and require further study. The role of neural mechanisms, hormonal pathways, and gut absorption are a few possibilities for targeted intervention to reduce the impact of obesity. Postnatal interventions for offspring could also be considered to reduce the chronic disease burden in the offspring. Drug development, including more potent GLP-1 receptor agonists, is revolutionizing obesity management and has exciting implications for women of reproductive age. The prevalence of surgical procedures is also increasing, with implications for the health of both the mother and the offspring. These surgical procedures, and emerging options such as Endobarrier © , requireIn view of the growing body of evidence regarding the transgenerational consequences of maternal obesity, it is paramount that efforts are directed to discover ways to ameliorate or mitigate the impacts of maternal obesity on adverse foetal programming. Overall, the evidence for the efficacy of weight modulation strategies during pregnancy is disappointing, and the preconception period is emerging as a time where meaningful gains may be made. Devising effective pre-pregnancy strategies, utilising diet modification, pharmacotherapy, or surgical intervention, are necessary to halt the transgenerational propagation of obesity. The utilisation of animal models to facilitate mechanistic and therapeutic discovery continues to be central to these discoveries. The ease of modelling, the reproductive potential, and the translational capacity of rodent models make them ideally placed to facilitate translation from bench to bedside discovery. Increasing the urgency of women with obesity of reproductive age to consider their fertility potential, plan pregnancy, and utilise intervention to improve pregnancy outcomes for themselves and their babies deserves increased public health attention worldwide.


The impact of climate-friendly agricultural practices on rural household productivity is not well understood, and the available evidence is mainly qualitative. Therefore, this study investigated the impact of the introduction of Climate-Smart Agriculture Practices  on the productivity of improved wheat producers of rural farmer households in Misha Woreda, the southern region of Ethiopia. For this study, we used the data collected from 202 randomly selected wheat producers through a structured questionnaire. The data were analyzed using propensity score matching (PSM) and the generalized Roy model of the semiparametric local instrument variable (LIV) method. The results of the PSM estimation showed that wheat row planting has a positive and significant impact on productivity. The study found that farmers who sowed wheat in a row produced 1368 kg of wheat per hectare compared to the counterfactual scenario. To further validate whether this result is a pure effect of the row planting technique, we performed a covariate balance test that confirmed the insensitivity of the treatment effect estimates to unobserved selection bias. In addition, the Marginal Treatment Effect (MTE) model also showed that the marginal utility of row planting adoption increases the propensity of farmers to adapt climate-smart agriculture technologies. Therefore, by increasing the productivity of farm households, the expansion of technology will significantly contribute to farmers' resilience to the harmful effects of climate change and welfare. Climate change is becoming a growing challenge to maintaining global food security that primarily affects the livelihoods of rural households in developing countries –3. MaintSince the introduction of the Climate Resilient Green Economy (CRGE) strategy in 2011, Ethiopia has built up climate-friendly agriculture. The design aims primarily to increase food security and improve farm income by introducing improved farming practices and infrastructure while protecting the quality of the environment. Climate-smart agricultural practices (CSA) are mainly yield-enhancing and reduce the challenges of climate variability . AdoptinMany agricultural technologies, such as fertilizers, improved varieties, and water management practices, have immense potential for increasing yields. However, they are capital intensive, less affordable, and therefore their adoption rate is lower. Thus, despite efforts to increase the uptake of these inputs, agricultural productivity is still at its lowest level, compounded by weak institutions, imperfections in the credit market, poor infrastructure, and the lack of advanced research and advisory systems . The conTo the best of our knowledge, there are few studies on the effects of row planting on household welfare . Tolosa et al.  studied Furthermore, the evidence on the superiority of row planting over traditional broadcasting methods is mainly qualitative and based on agronomic knowledge ; Abraha Against this background, our study aims to assess the impact of row planting on wheat productivity of rural smallholder households in the district of Misha, South Nation, and Nationalities Region, and the contribution of our study is manifold. First, we measure smallholder farmers' welfare in productivity (wheat yield/ha). Second, we applied Propensity Score Matching (PSM) with the generalized Roy model's semiparametric Local Instrumental Variable (LIV) method. The Roy model is superior to the linear endogenous treatment effects and maximum likelihood estimation of switching regression because the Roy-LIV model estimates the marginal treatment effect (MTE) and the average treatment effect (ATE) of the adoption decision . In addihypothesis 1: Row-planting technique enhances the productivity of smallholder farmershypothesis 2: Row-planting adoption increases the marginal utility of farmers to adapt climate-smart agriculture practices.Therefore, the major objective of this study is to investigate the impact of climate-smart agriculture practices on rural household welfare in the southern region of Ethiopia. First, our study investigated the quantitative impact of wheat row planting on the productivity of smallholder farmers. Second, the study examined the marginal treatment effect of row planting adoption. Based on these objectives, our study forwarded the following hypothesis.We organized the rest of our work as follows. Wheat is an important food crop grown in the highland areas of Ethiopia. It plays an essential role in maintaining food security and poverty alleviation in Ethiopia . In addiWheat is a strategic staple in Africa, and its demand increases over time due to income growth and urbanization. However, sub-Saharan countries produce around 30% of their domestic needs, meaning these countries are heavily dependent on imports. Dependence on imports carries the risk of commodity price volatility and supply shocks . In EthiTo increase productivity, climate-friendly farming practices have recently been introduced, including row plantings. This production technology has several advantages that we cannot achieve with the traditional broadcast method. For example, planting in rows helps increase the spacing between plants, allowing better access to water and sunlight and reducing the amount of seed.This study was conducted in the Misha district of southern Ethiopia using household-level survey data collected through a structured questionnaire. According to the population projection of the Central Statistical Office, the Mischa district had 170,490 inhabitants in July 2021; of that, 48.6 per cent were men and 51.4 per cent were women. Around 95 per cent of the population lives in rural areas and depends on agriculture. The Misha District has three agro-climatic zones: lowland , mid-altitude , and highland  . The mosWe used a multistage sampling method to select the study participants. For this study, we first purposively chose Misha Woreda because wheat is the dominant crop in the area. Second, we selected three kebele , namely Gidasha, Ololico, and Forks kebele, that primarily produce wheat. Third, we randomly select 202 households that produce improved wheat from the three kebele. Of that, 83 households are adopters and 119 households are nonadopters of row planting technology in their wheat farm. The sample size was determined based on the proportion to the size of the household in each kebele. In the first step, we selected those farmers who produce improved wheat varieties in the study area. In the second phase, we divided these farmers into producers of an improved wheat variety using row seeding technology and traditional broad seeding technology. Finally, we randomly selected wheat producers from each treatment status category in the kebele sample and collected the data through a structured questionnaire in the 2018/19 cropping season.The main challenge in evaluating an intervention or program is obtaining a credible counterfactual estimate: What would have happened to the participating units if they had not participated? . TherefoY1–Y0. This is the difference between the outcome of the treatment group and the controlled groups. However, although it is mathematically simple, estimating impacts using the above equation leads to a “lack of data problem” referred to in the program evaluation literature [Based on Heckman et al. , one canterature . One priterature . TherefoZi is the binary treatment variable and indicates the treatment status of the household i; it takes on the value one of the households adopted row planting and zero, otherwise (adopted broadcasting method), and Xi is the set of controlled covariates. E  refers to the mean outcome for the treatment group, and E  refers to the mean outcome of the controlled group. While the mean outcome for the treated group is observable, the mean outcome for the untreated group is not. Therefore, we need to find groups that share characteristics similar to the treatment group to arrive at an accurate estimate of the average treatment effect (ATT). To this end, we used a propensity score matching method to find a controlled group that matched with the treatment group and to estimate the average treatment effect of adopting wheat row plantings. In the empirical literature, there have been different approaches to estimating the treatment effects. Other approaches, such as the endogenous switching regression model [Thus, for our study, the average treatment effect on treated (ATT) is given by the following:on model –36 and eon model , 37, canon model –41.Z between the treatment and matched comparison group samples. If the standardized bias difference is greater than 20%, it signals a failure of the match. However, our results are insensitive to hidden biases.A covariate balancing test is required to control the bias and see if it changes after matching, making the matching group an appropriate counterfactual for the treated group. However, there are different versions of balance tests in the literature . AccordiA major problem with propensity score matching is that it fails to account for unobserved heterogeneity. Therefore, we fitted the generalized Roy model with local instrumental variables to complement the propensity score matching results. As a result, the Roy model underpins the selection of unobservable factors, estimates the marginal treatment effect, and the mean treatment effect of the decision to enter treatment using parametric and nonparametric approaches .After a thorough analysis of the related empirical literature, we selected the variables presented in Compared to nonadopters of row planting technology, adopters are male, have larger household sizes, are younger, are closer to advisory offices, are cooperative members, have more social roles, and are involved in nonfarm activities. The average household size of adopters is 4.5 people compared to 4.4 people for nonadopters, although the difference is statistically insignificant. The choice of wheat row planting is positively associated with access to market information, membership in cooperatives, social role, and off-farm income. Access to these institutional services could help farmers adapt yield-enhancing technologies. Because, on the one hand, farmers have the opportunity to observe, learn, and develop knowledge about the use and application of improved technologies, and on the other hand, farmers become risk-takers. Adopters also consume more fertilizers and have larger farm sizes compared to nonadopters.The other important variable is the outcome variable, that is, wheat productivity as measured by yield per hectare of land. Adopters have higher wheat productivity than nonadopters. There is a significant difference in the average productivity of wheat production between users and nonusers of the row sowing method. Adopters produce about 21 quintals (2124.696 kg/ha) per hectare, and nonadopters produce eight quintals (800.489 kg/ha) per hectare of land, which is significant at the 1 per cent significance level.Finally, we asked respondents about their reasons for adopting row planting technology in their production. Approximately 90% of adopter respondents cited improving productivity, reducing seed requirement (70%), and easing weeding (40%) as the first, second, and third reasons for adopting row planting. Similarly, we asked the nonadopters why they did not apply the row-planting method in their wheat production. Accordingly, about 85% of them reported that the technology is labor intensive and time-consuming. The result prompts the need to use complementary technologies, such as agricultural mechanization, that reduce labor and time requirements, thereby increasing nonuser's acceptance of row planting technology.This section highlights the estimation of propensity scores and matching based on the propensity score. After calculating the propensity score, we produced the matched controls with the corresponding treatment samples. Then we assessed the average treatment effects on persons treated (ATT) based on the matched households.The outcome of the selection model also shows that a male householder is positively associated with the adoption of row planting technology. Male-headed households are 31.7 per cent more likely to adapt than their female counterparts are. The result is similar to the results of Admassie & Ayele , who argAge is another variable positively associated with household adoption decisions, but only limited. The effect of the age of the household head on technology adoption was not clear in the literature , 46. On Among the institutional variables, membership in cooperatives is positively associated with row planting technology. Farmer's membership in cooperatives significantly increases the probability of adoption by 26.9 percentage points. Because cooperatives serve as a source of information, provide inputs and offer training of various kinds to enable farmers to develop new skills in using new technologies and become more risk-takers. The role of cooperative membership in promoting agricultural technology adoption has been widely proved in the literature, and our findings are in line with the findings of , 48, 49.After estimating the logit model using the covariates in p-value of LR (χ2) is 0.935. Thus, the distribution of covariates between the treated and control groups is balanced after matching.We plot the common region of support that balances household characteristics between adopters and nonadopters of row planting technology using the predicted propensity score. The presence of a significant number of samples of the two groups in the common support region indicates the presence of an appropriate balance in the distribution of covariates between the treated and controlled samples. When covariate imbalances occur, it is just accidental. To check the fulfillment of the balancing condition, we introduced the common support condition in the estimation by matching the region of common support. Using four comparative techniques, we estimated the effects of adopting row-planting technology on the welfare of farmers' growing improved wheat. These techniques are the nearest neighbor (NN) matching, radius matching, kernel matching, and stratification matching algorithms. Estimations are using Bootstrap standard errors.The estimates of all matching techniques showed the positive and significant effect of row planting on wheat productivity for the treated groups. As shown in Despite the difference in the size of the average treatment effect from using all matching algorithms, row planting has a positive effect that shows its essential role in increasing wheat productivity for the treated farmers. Therefore, our result has implications for broadcasters that should produce wheat by sowing in a row instead of using the traditional broadcast method.Sensitivity analysis verifies the sensitivity of the estimated treatment effect to small deviations in the model's specification, which is a strong assumption that must be maintained to have the pure effect of interventions on outcome variables. In the empirical literature, Rosenbaum & Rubin  recommenThe results of semiparametric LIV are similar to those of propensity score matching with positive mean treatment effects. The marginal treatment effect (MTE) increases with a higher probability of participating in the treatment. The MTE is estimated using the semiparametric LIV method with values within the common support of the predicted propensity scores. Accordingly, as shown in The empirical evidence shows that the relationship between climate-smart agricultural technologies and their impact on well-being is unexplored, and the available evidence is mixed. It is challenging to find appropriate methods to analyze the quantitative impacts of climate-friendly practices, and therefore, there are few studies on the uptake of climate-smart agriculture technologies and their impact on the productivity of rural farm households. Therefore, this study examined the effects of CSA (row planting) technology on wheat-producing farm households' welfare (measured in terms of productivity) using state-of-the-art analysis methods. We used propensity score matching and the semiparametric LIV method to estimate the mean treatment effect of introducing row plantings to treated sample households. In addition, the sensitivity analysis of the estimated treatment effects using the Rosenbaum limit method is verified, and the ATT estimates are the pure effects of applying the row planting technique.The results of our study showed the significant and positive contribution of row planting technology to the productivity of wheat-producing farmers. Propensity Score Matching created appropriate matching samples for the treatment groups, and the estimates confirm that the average productivity of the row seeders is higher than that of the broadcasters. Furthermore, as confirmed by the sensitivity analysis, the treatment effect is free from hidden bias. Thus, for adopter households, the increase in productivity is associated only with sowing wheat in rows. We also estimated the marginal treatment effect of introducing row plantings using the semi-parametric LIV model. The results showed that the marginal benefit of adopting row-planting increases as the likelihood of farmers adapting climate-smart agriculture practices.Our study also explained why farmers use row planting technology for those who adapt it and why they do not use it for nonusers. Accordingly, a more significant proportion of adopters responded that the need for productivity and ease of weeding are the main reasons for adopting the technology. On the other hand, nonadopters reported that labor and time limitations are the challenges of adopting the technology. Therefore, efforts to disseminate this technology should focus on helping farmers with labor allocation and time management or helping them by providing agricultural mechanization (reducing the need for labor).Our result showed that education, gender, age, and cooperative membership are strongly associated with row planting adoption. The main implication is that the positive impact of introducing row planting on farmer productivity could be enhanced by encouraging farmer membership in cooperatives, supporting female-headed households with farm information and access to formal credit, and increasing access to education.The results of our study correspond to similar studies on the introduction of agricultural technology. Further expansion of the technology to other but similar geographic features could increase farmer acceptance of the technology and improve farm household well-being by increasing productivity. Aside from these, farmers exposure to climate change could also be less since the technology is climate-friendly. However, we encourage other researchers interested in this area to analyze large datasets across different geographical regions to generalize the results on a larger scale.