A novel PAX9 variant in a Chinese family with non-syndromic oligodontia and genotype-phenotype analysis of PAX9variants.

OBJECTIVES: This study aimed to identifyPAX9variants in non-syndromic tooth agenesis families of China, as well as to analyze the genotype⁃phenotype of non-syndromic tooth agenesis caused by PAX9variants, which can provide a basis for the genetic diagnosis of tooth agenesis. METHODS: We collected the data of 44 patients with non-syndromic oligodontia who underwent treatment at Stomatological Hospital of Hebei Medical University between 2018 and 2023. Whole-exome sequencing was performed on the peripheral blood of the proband and its core family members, and the variants were verified by Sanger sequencing. Pathogenicity analysis and function prediction of the variants were performed using bioinformatics tools. The correlation between the genotype of PAX9 variant and its corresponding phenotype was examined by reviewing 55 publications retrieved from PubMed. The studies involved 232 tooth agenesis patients with PAX9 variants. RESULTS: A novel PAX9 c.447delG (p.Pro150Argfs*62) and a reported PAX9 c.406C>T (p.Gln136*) were identified in two Chinese families. Through bioinformatics analysis and three-dimensional structural modeling, we postulated that the frameshift variant was pathogenic. The outcome was the premature cessation of PAX9 protein, which caused severe structural and functional deficiencies. Summarizing the PAX9 genotype-phenotype relationship revealed that patients carrying the PAX9 variant commonly led to loss of the second molars. CONCLUSIONS: We identified the novel PAX9 c.447delG (p.Pro150Argfs*62) in a Chinese family of non-syndromic oligodontia, expanding the known variant spectrum of PAX9. The most susceptible tooth position for PAX9 variants of tooth agenesis was the second molars and the deciduous molars during the deciduous dentition.

The interaction between gut microbiota and hibernation in mammals.

Hibernation, an evolved survival trait among animals, enables them to endure frigid temperatures and food scarcity during the winter months, and it is a widespread phenomenon observed in mammals. The gut microbiota, a crucial component of animal nutrition and health, exhibits particularly dynamic interactions in hibernating mammals. This manuscript comprehensively evaluates the impacts of fasting, hypothermia, and hypometabolism on the gut microbiota of hibernating mammals. It suggests that alterations in the gut microbiota may contribute significantly to the maintenance of energy metabolism and intestinal immune function during hibernation, mediated by their metabolites. By delving into these intricacies, we can gain a deeper understanding of how hibernating mammals adapt to their environments and the consequences of dietary modifications on the symbiotic relationship between the gut microbiota and the host. Additionally, this knowledge can inform our comprehension of the protective mechanisms underlying long-term fasting in non-hibernating species, including humans, providing valuable insights into nutritional strategies and health maintenance.

Metabolic profiling and spatial metabolite distribution in wild soybean (G. soja) and cultivated soybean (G. max) seeds.

Wild soybeans retain many substances significantly reduced or lost in cultivars during domestication. This study utilized LC-MS to analyze metabolites in the seed coats and embryos of wild and cultivated soybeans. 866 and 815 metabolites were identified in the seed extracts of both soybean types, with 35 and 10 significantly differing metabolites in the seed coat and embryos, respectively. The upregulated metabolites in wild soybeans are linked to plant defense, stress responses, and nitrogen cycling. MALDI-MSI results further elucidated the distribution of these differential metabolites in the cotyledons, hypocotyls, and radicles. In addition to their role in physiological processes like growth and response to environmental stimuli, the prevalent terpenoids, lipids, and flavonoids present in wild soybeans exhibit beneficial bioactivities, including anti-inflammatory, antibacterial, anticancer, and cardiovascular disease prevention properties. These findings underscore the potential of wild soybeans as a valuable resource for enhancing the nutritional and ecological adaptability of cultivated soybeans.

Glyphosate resistance and no fitness cost in backcross offspring of wild soybean and transgenic soybean with epsps gene.

BACKGROUND: The commercial utilization of genetically modified soybeans has yielded substantial economic advantages. Nevertheless, the genetic drift towards wild soybeans is one of the main ecological risks that needs to be addressed. Previous experiments demonstrated the absence of fitness cost or florescence overlap in hybrid offspring resulting from the crossbreeding of transgenic soybean GTS40-3-2 and Zhengzhou wild soybeans. In this study, hybrid progeny was systematically crossed with wild soybeans to establish a backcross progeny system. This system was employed to evaluate the ecological risk associated with the backcross progeny of transgenic and wild soybeans. RESULTS: The findings indicated that the offspring from the backcross exhibited glyphosate tolerance. Furthermore, the expression of foreign proteins in the backcross offspring was notably lower than in the transgenic soybean, and there was no significant difference when compared to the hybrid progeny. Parameters such as germination rate, aboveground biomass, pods per plant, full seeds per plant, and 100-grain weight exhibited no significant differences between the negative and positive lines of the backcross progenies, and no fitness cost was identified in comparison to wild soybeans. These results underscore the potential for foreign genes to propagate within other wild soybeans, which requires continuous attention. CONCLUSIONS: The widespread adoption of genetically modified soybeans has undeniably led to substantial economic gains. However, the research findings emphasize the critical importance of addressing the ecological risks posed by genetic drift towards wild soybeans. The backcross progeny system established in this study indicates that the potential for foreign gene dissemination to wild soybean populations warrants continued attention and mitigation strategies.

The Impact of High-Temperature Stress on Gut Microbiota and Reproduction in Siberian Hamsters (Phodopus sungorus).

Global warming has induced alterations in the grassland ecosystem, such as elevated temperatures and decreased precipitation, which disturb the equilibrium of these ecosystems and impact various physiological processes of grassland rodents, encompassing growth, development, and reproduction. As global warming intensifies, the repercussions of high-temperature stress on small mammals are garnering increased attention. Recently, research has highlighted that the composition and ratio of gut microbiota are not only shaped by environmental factors and the host itself but also reciprocally influence an array of physiological functions and energy metabolism in animals. In this research, we combined 16S rRNA high-throughput sequencing with conventional physiological assessments, to elucidate the consequences of high-temperature stress on the gut microbiota structure and reproductive capacity of Siberian hamsters (Phodopus sungorus). The results were as follows: 1. The growth and development of male and female hamsters in the high-temperature group were delayed, with lower body weight and reduced food intake. 2. High temperature inhibits the development of reproductive organs in both female and male hamsters. 3. High temperature changes the composition and proportion of gut microbiota, reducing bacteria that promote reproduction, such as Pseudobutyricoccus, Ruminiclostridium-E, Sporofaciens, UMGS1071, and CAG_353. Consequently, our study elucidates the specific impacts of high-temperature stress on the gut microbiota dynamics and reproductive health of Siberian hamsters, thereby furnishing insights for managing rodent populations amidst global climatic shifts. It also offers a valuable framework for understanding seasonal variations in mammalian reproductive strategies, contributing to the broader discourse on conservation and adaptation under changing environmental conditions.

Flavonoid localization in soybean seeds: Comparative analysis of wild (Glycine soja) and cultivated (Glycine max) varieties.

Wild soybean (Glycine soja) is known for its high flavonoid contents, yet the distribution of flavonoids in the seeds is not well understood. Herein, we utilized matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) and metabolomics methods to systematically investigate flavonoid differences in the seed coats and embryos of G. soja and G. max. The results of flavonoid profiles and total flavonoid content analyses revealed that flavonoid diversity and abundance in G. soja seed coats were significantly higher than those in G. max whereas the levels were similar in embryos. Specifically, 23 unique flavonoids were identified in the seed coats of G. soja, including procyanidins, epicatechin derivatives, and isoflavones. Using MALDI-MSI, we further delineated the distribution of the important flavonoids in the cotyledons, hypocotyls, and radicles of the two species. These findings imply that G. soja holds considerable breeding potential to enhance the nutritional and stress resistance traits of G. max.

Gender differences in brain region activation during verbal fluency task as detected by fNIRS in patients with depression.

BACKGROUND: Gender plays a role in the mechanisms of depression, but fewer studies have focused on gender differences in the abnormal activation of brain regions when patients perform specific cognitive tasks. METHODS: A total of 110 major depressive disorder (MDD) patients and 106 healthy controls were recruited. The relative change in oxygen-haemoglobin (oxy-Hb) concentration during the verbal fluency task were measured by a 52-channel near-infra-red spectroscopy (NIRS) system. Differences in brain region activation between patients and healthy controls and between genders of depression patients were compared. RESULTS: MDD patients demonstrated significantly decreased [oxy-Hb] changes in the right inferior frontal gyrus (p = 0.043) compared to healthy controls. A marked increase in leftward functional language lateralisation in the inferior frontal gyrus was observed in the MDD group in contrast to the HC group (p = 0.039). Furthermore, female patients in the MDD group exhibited significant reductions in [oxy-Hb] changes in the right frontal region (specifically, the superior and middle frontal gyrus; p = 0.037) compared with male patients. CONCLUSIONS: Gender impacts depression-related brain activation during cognitive tasks, potentially influencing depression's pathogenesis.

Characterization of novel MSX1 variants causally associated with non-syndromic oligodontia in Chinese families.

BACKGROUND: MSX1 (OMIM #142983) is crucial to normal dental development, and variants in MSX1 are associated with dental anomalies. The objective of this study was to characterize the pathogenicity of novel MSX1 variants in Chinese families with non-syndromic oligodontia (NSO). METHODS: Genomic DNA was extracted from individuals representing 35 families with non-syndromic oligodontia and was analyzed by Sanger sequencing and whole-exome sequencing. Pathogenic variants were screened via analyses involving PolyPhen-2, Sorting-Intolerant from Tolerant, and MutationTaster, and conservative analysis of variants. Patterns of MSX1-related NSO were analyzed. MSX1 structural changes suggested functional consequences in vitro. RESULTS: Three previously unreported MSX1 heterozygous variants were identified: one insertion variant (c.576_577insTAG; p.Gln193*) and two missense variants (c. 871T>C; p.Tyr291His and c. 644A>C; p.Gln215Pro). Immunofluorescence analysis revealed abnormal subcellular localization of the p.Gln193* MSX1 variant. In addition, we found that these MSX1 variants likely lead to the loss of second premolars. CONCLUSION: Three novel MSX1 variants were identified in Chinese Han families with NSO, expanding the MSX1 variant spectrum and presenting a genetic origin for the pathogenesis detected in patients and their families.

Seed coat colour and structure are related to the seed dormancy and overwintering ability of crop-to-wild hybrid soybean.

The possible persistence of genetically modified (GM) crop-to-wild hybrid seeds in the soil seed bank is a major concern in risk assessment and is closely related to seed characteristics such as dormancy. In the present study, we generated F3 hybrids via crosses between GM soybean accessions and wild soybean and evaluated the dormancy, overwintering ability and inheritance of foreign genes in different-coloured hybrid seeds (yellow, green, brown and black). The results revealed that the 5-enolpyruvylshikimate-3-phosphate synthase transgene may have no influence on crop wild hybrid seed dormancy and overwintering ability, and the dormancy of the hybrid seeds was closely related to seed coat colour. F3 hybrid seeds with light colours (yellow and green) were relatively nondormant, while seeds that were dark (brown and black) in colour were relatively dormant. Moreover, the hybrid seeds that were dark in colour had a much stronger overwintering ability than the lighter-coloured seeds, with 21.33 % of the black seeds and 33.33 % of the brown seeds remaining viable after 240 days of soil burial. In contrast, almost all the F3 yellow and green seeds were no longer viable during winter. Scanning electron microscopy revealed that the lighter-coloured seeds had a thin palisade layer and very few surface deposits, while the darker-coloured seeds had a thicker palisade layer and a large area of honeycomb-like surface deposits similar to those of wild soybean seeds. Thus, the physical dormancy and overwintering ability of the darker-coloured seeds may be related to the seed coat. Our results suggest that transgenes of GM soybean might disperse into wild populations and persist in seed banks.

Full-space wavefront control enabled by a bilayer metasurface sandwiching 1D photonic crystal.

Metasurfaces, composed of sub-wavelength structures, have a powerful capability to manipulate light propagations. However, metasurfaces usually work either in pure reflection mode or pure transmission mode. Achieving full-space manipulation of light at will in the optical region is still challenging. Here we propose a design method of full-space meta-device containing a bilayer metasurface sandwiching 1D photonic crystal to manipulate the transmitted and reflected wave independently. To provide a proof-of-concept demonstration, a device is proposed to show the light focusing in transmission and a vortex beam in reflection. Meanwhile, a device focusing the reflected light with oblique 45° incidence and the transmitted light with normal incidence is designed to indicate its application potential in augmented reality (AR) application. Our design provides a promising way to enrich the multifunctional meta-devices for potential applications.

Spindle Nanorods of CeO2 and NiS Heterointerface Coated by the NC Layer: A High-Performance Bifunctional Electrocatalyst for Water Splitting.

Currently, nickel sulfides are widely employed in the oxygen evolution reaction (OER) and hydrogen evolution reaction (HER), thanks to the narrow electronegativity difference of only 0.67 eV between nickel and sulfur. Among them, NiS stands out in terms of the OER performance; however, its HER performance and stability remain somewhat inadequate. The construction of heterogeneous interfaces can efficiently improve the HER performance and regulate the electronic structure of the NiS catalyst. CeO2 has been discovered to possess exceptional electronic modulation capabilities, which may lead to the effective enhancement of both HER and OER of the NiS catalyst. As a result, a nitrogen-doped carbon-coated CeO2-NiS heterogeneous interface catalyst (NC/NiS-CeO2) is designed as a bifunctional electrocatalyst for HER and OER with high performance. The NC/NiS-CeO2 catalyst demonstrates excellent HER (47 mV at 10 mA cm-2) and OER (92 mV at 10 mA cm-2) performances in a 1 M KOH alkaline solution. Characterization analysis reveals that the coupling of the heterostructure interface, which consists of CeO2 and NiS, significantly enhances electron conduction, the synergistic effect, and the electrocatalytic activity of the electrode. This study demonstrates that the HER and OER activity can be effectively improved by constructing a rational heterogeneous interface.

RuSe2-CoTe Heterogeneous Surfaces Coated with NC Layer for Excellent HER Performance under Alkaline Condition.

Electrocatalytic hydrogen production has been a promising high-purity hydrogen production technology, attracting a large number of researchers' research interest. Ru has a hydrogen binding capacity similar to Pt, but its price is far lower than Pt, making it a promising alternative to Pt. However, a single Se electronic structure modulation is not sufficient to enable RuSe2 to be used for practical applications on a large scale due to the lack of electrons. Therefore, choosing a suitable way to electronically modulate the Ru atoms in RuSe2 can effectively improve the activity of the catalyst. Cobalt telluride (CoTe) can significantly enhance electrocatalytic performance due to tellurium's low electronegativity and excellent metal properties. In this work, the NC layer possesses excellent electrical conductivity and CoTe acts as an electron donor to optimize the electronic structure locally and trigger electron transfer efficiently. The RuSe2-CoTe/NC electrode requires an overpotential of only 25.4 mV (10 mA cm-2), which is superior to that of RuSe2/NF (65 mV) and CoTe/NC (115 mV). Meanwhile, the Tafel slope of RuSe2-CoTe/NC (67.8 mV dec-1) was better than that of RuSe2/NF (113.6 mV dec-1) and CoTe/NC (209.5 mV dec-1), showing that the build-up of the superior heterojunction makes the RuSe2-CoTe/NC with better hydrogen evolution reaction (HER) reaction kinetics. In addition, after 30 h of long-term stability testing, no significant decrease in catalytic activity was observed, proving the good stability of the RuSe2-CoTe/NC catalyst.

Oxygen-Doped Red Carbon Nitride: Enhanced Charge Separation and Light Absorption for Robust CO2 Photoreduction.

Utilizing artificial photosynthesis for the conversion of CO2 into value-added fuels has been recognized as a promising strategy for the ever-increasing energy crisis and the greenhouse effect. Herein, the element doping engineering of red spherical g-C3N4 having oxygen bonded with compositional carbon (C-O-C) for CO2 photoreduction has been explored to address this challenge. The C-O bond was formed by hydrothermal treatment with dicyandiamide and 1,3,5-trichlorotriazine. The experimental and DFT results displayed the optimum oxygen substitution sites and demonstrated that the oxygen doping greatly improved the light utilization efficiency, CO2 affinity, and charge carrier transfer, which enhanced photoreduction efficiency of CO2. The evolution rates of CO (47.2 µmol g-1) and CH4 (9.1 µmol g-1) using O-CN were much higher than that of bulk-CN without a cocatalyst. The main reason was the contribution of the O 2p orbital to the conduction band (CB) and valence band of O-CN, which effectively reduced the electron mass, facilitating electron/hole separation and enhancing its fluidity. Furthermore, the Fermi level also shifted to the bottom of the CB, leading to higher electron density, which further improved the CO2 reduction ability. Our study marks an important step for developing high-performance photocatalysts for reduction of CO2.

Fitness changes in wild soybean caused by gene flow from genetically modified soybean.

BACKGROUND: Crop-wild hybridization has generated great concerns since gene flow can be an avenue for transgene escape. However, a rather limited number of studies on risk assessment regarding the dispersion of transgenes from GM soybean to populations of its wild relatives have been previously conducted. RESULTS: The results of the 3-year experiment demonstrated that hybrids between GM soybeans and wild soybean had lower seed germination and higher seed productivity than GM soybean. Both of these features of hybrid (especially F2 and F3) were similar to those of wild soybean. Furthermore, the foreign protein was stably expressed in hybrid EPSPS positive plants; however, no difference was observed in agronomic measurements between hybrids that are glyphosate sensitive or resistant, homozygous or heterozygous for the transgene, indicating that the presence of the EPSPS transgene does not affect the vigor of hybrid. In contrast, hybridization between GM soybean and wild soybean may have more impact on hybrid growth and fecundity, this increase in biomass and yield confers a potential competition benefit to hybrids. CONCLUSIONS: Gene flow from GM soybean to wild soybean has the potential to promote the adaptability of hybrids and may increase the possibility of dispersal of transgenes in wild soybean relatives.

Impacts of climate change on herpetofauna diversity in the Qinghai-Tibetan Plateau.

Although numerous studies on the impacts of climate change on biodiversity have been published, only a handful are focused on the intraspecific level or consider population-level models (separate models per population). We endeavored to fill this knowledge gap relative to the Qinghai-Tibetan plateau (QTP) by combining species distribution modeling (SDMs) with population genetics (i.e., population-level models) and phylogenetic methods (i.e., phylogenetic tree reconstruction and phylogenetic diversity analyses). We applied our models to 11 endemic and widely distributed herpetofauna species inhabiting high elevations in the QTP. We aimed to determine the influence of environmental heterogeneity on species' responses to climate change, the magnitude of climate-change impacts on intraspecific diversity, and the relationship between species range loss and intraspecific diversity losses under 2 shared socioeconomic pathways (SSP245 and SSP585) and 3 future periods (2050s, 2070s, and 2090s). The effects of global climatic change were more pronounced at the intraspecific level (22% of haplotypes lost and 36% of populations lost) than the morphospecies level in the SSP585 climate change scenario. Maintenance of genetic diversity was in general determined by a combination of factors including range changes, species genetic structure, and the part of the range predicted to be lost. This is owing to the fact that the loss and survival of populations were observed in species irrespective of the predicted range changes (contraction or expansion). In the southeast (mountainous regions), climate change had less of an effect on range size (>100% in 3 species) than in central and northern QTP plateau regions (range size <100% in all species). This may be attributed to environmental heterogeneity, which provided pockets of suitable climate in the southeast, whereas ecosystems in the north and central regions were homogeneous. Generally, our results imply that mountainous regions with high environmental heterogeneity and high genetic diversity may buffer the adverse impacts of climate change on species distribution and intraspecific diversity. Therefore, genetic structure and characteristics of the ecosystem may be crucial for conservation under climate change.

Impactos del cambio climático sobre la diversidad de herpetofauna en la meseta Qinghai-Tíbet Región Aunque se han publicado numerosos estudios sobre los impactos del cambio climática en la biodiversidad, son muy pocos los que se enfocan en el nivel intraespecífico o que consideran modelos a nivel poblacional (modelos separados por población). Intentamos cerrar este vacío de conocimiento en relación con la meseta Qinghai-Tíbet (MQT) con la combinación entre modelos de distribución de especies (MDE) y genética poblacional (modelos a nivel poblacional) y métodos filogenéticos (reconstrucción de árboles filogenéticos y análisis de diversidad filogenética). Aplicamos nuestros modelos a once especies endémicas de herpetofauna con distribución amplia en las elevaciones más altas de la MQT. Nos planteamos determinar la influencia de la heterogeneidad de las especies sobre la respuesta de las especies al cambio climático, la magnitud de los impactos del cambio climático sobre la diversidad intraespecífica y la relación entre la pérdida de distribución de la especie y las pérdidas de diversidad intraespecífica bajo dos vías socioeconómicas (SSP245 y SSP585) y tres periodos del futuro (2050s, 2070s y 2090s). Los efectos del cambio climático global fueron más pronunciados a nivel intraespecífico (22% de pérdida en los haplotipos y 36% en las poblaciones) que al nivel morfoespecie en el escenario de cambio climático SSP585. El mantenimiento de la diversidad genética casi siempre estuvo determinado por una combinación de factores que incluyen cambios en la distribución, estructura genética de las especies y la parte de la distribución que se pronosticó se perdería. Esto se debe a que observamos la pérdida y supervivencia de las poblaciones sin importar los cambios pronosticados en la distribución (contracción o expansión). En las regiones montañosas del sureste, el cambio climático tuvo un efecto menor sobre la distribución (>100% en tres especies) comparado con las regiones de la meseta central y del norte de la MQT (distribución <100% en todas las especies). Esto puede atribuirse a la heterogeneidad ambiental, la cual proporciona recovecos de clima adecuado en el sureste, mientras que los ecosistemas en las regiones central y norte fueron homogéneos. De manera general, nuestros resultados implican que las regiones montañosas con una elevada heterogeneidad ambiental y una gran diversidad genética podrían reducir los impactos adversos del cambio climático sobre la distribución de las especies y la diversidad intraespecífica. Por lo tanto, la estructura genética y las características del ecosistema pueden ser cruciales para conservar bajo el cambio climático.

Fabrication of multiphase MoSe2 modified BiOCl nanosheets for efficient piezo-photoelectric hydrogen evolution and antibiotic degradation.

Efficient spatial charge separation plays a crucial role in improving the photocatalytic performance. Therefore, 1T/2H MoSe2/BiOCl (1T/2H MS/BOC) and 2H MoSe2/BiOCl (2H MS/BOC) piezo-photocatalysts are synthesized. By combining piezoelectric catalysis and photocatalysis, a highly active piezo-photocatalytic process is realized. The optimal 1T/2H MS/BOC piezo-photocatalyst displays superior diclofenac (DCF) degradation and hydrogen (H2) evolution activity under the combined action of ultrasound and light. In particular, the DCF degradation kinetic constant (k) of optimal 0.5% 1T/2H MS/BOC under the synergistic effect of ultrasound and light is 0.057 min-1, which is 8.1 and 6.3 times higher than those of BiOCl (0.007 min-1) and 0.5% 2H MS/BOC (0.009 min-1). Moreover, the H2 evolution rate of 0.5% 1T/2H MS/BOC is 122.5 µmol g-1 h-1, which is also higher than those of BiOCl (45.8 µmol g-1 h-1) and 2H MS/BOC (49.5 µmol g-1 h-1). The dramatic improvement in the DCF degradation and H2 evolution piezo-photocatalytic performance of 1T/2H MS/BOC catalysts is ascribed to the built-in polarization electric field and abundance of active sites of 1T/2H MS/BOC as well as the advantageous band structure between BiOCl and 1T/2H MoSe2. Additionally, three probable degradation pathways of DCF were put forward from the results of liquid chromatography-mass spectrometry (LCMS) and density functional theory (DFT) calculations. This study provides the design strategy of high efficiency piezo-photocatalysts in environmental purification and energy-generation fields based on phase and band structure engineering.

Optimization of a concentrated growth factor/mesoporous bioactive glass composite scaffold and its application in rabbit mandible defect regeneration.

Maxillofacial bone defect repair and regeneration remains a tremendous challenge in the field of stomatology. However, the limited osteoinductivity of artificial materials and the high cost of bioactive agents restrain their clinical translation. This study aimed to construct an economical and efficient concentrated growth factor/mesoporous bioactive glass (CGF/MBG) composite scaffold for bone regeneration. The biochemical composition and biological effects of different forms of CGFs were systematically compared, and the results showed that CGF-conditioned medium effectively promoted proliferation, migration and osteogenesis of allogenic BMSCs. Gel phase CGF (gpCGF) exhibited superior bioactivity and osteoinductivity to liquid phase CGF (lpCGF) and liquid/gel mixed phase CGF (lgpCGF), and was further applied to construct CGF/MBG scaffolds. In vitro studies demonstrated that co-culture with gpCGF-conditioned medium further enhanced the biocompatibility of MBG, increasing cell adhesion and proliferation on the scaffold. On this basis, two compositing approaches to construct the scaffold by fibrin gel formation (CGF/FG/MBG) and freeze-drying (fdCGF/MBG) were applied, and the biological efficacy of CGFs was compared in vivo. In a rabbit mandibular defect model, higher osteogenic efficiency in in situ bone regeneration of CGF/FG/MBG composite scaffolds was proved, compared with fdCGF/MBG. Taken together, the CGF/FG/MBG composite scaffold is expected to be an efficient bone repairing therapy for clinical translation, and the CGF-composited scaffold using gpCGF and the fibrin gel formation method is a promising way to enhance the bioactivity and osteoinductivity of current clinical bone repairing materials, providing new thoughts on the development of future orthopedic biomaterials.

Bibliometric and visualized analysis of the top-100 highly cited articles on immunotherapy for endometrial cancer.

BACKGROUND: Immunotherapy is a promising method for the treatment of endometrial cancer (EC). We aimed to conduct a comprehensive bibliometric study of the top 100 most-cited publications on immunotherapy for EC and provide a reference for future research. METHODS: Global publications on immunotherapy for EC published from 1985 to the present in the Web of Science core database were retrieved. We focused on the study of the top 100 most-cited articles by extracting information such as year, country, journal, author, institution, literature, and keywords. Microsoft Excel, VOSviewer, and R were used to perform descriptive statistics and visual analyses. RESULTS: The top 100 most-cited articles were published between 2002 and 2022, including 70 original papers and 30 reviews. The total frequency of citations per article ranges from 15 to 287. Developed countries dominated these publications, with the United States contributing the most (50 articles). According to Bradford Law, 6 journals, including Gynecologic Oncology and the Journal of Clinical Oncology, are highly recommended. Santin A. D. from Yale University and Makker.V. from Memorial Sloan Kettering Cancer Center have made positive contributions. Among the top ten most-cited articles, 7 focused on clinical trials exploring the efficacy of immunotherapy drugs, of which 4 were lenvatinib combined with pembrolizumab for the treatment of advanced EC. The immune-microenvironment, immune antitumor mechanisms, immunomodulatory drugs, especially anti-pd-1/pd-l1 checkpoint inhibitors, and their clinical trials are the focus of current research. CONCLUSION: The attention of researchers from different countries to EC immunotherapy, especially immunosuppressants, has brought a breakthrough in this field. A large number of clinical trials have evaluated the efficacy and safety of immune agents, and immune combination therapy (especially targeted therapy) shows positive therapeutic promise. Immunodrug sensitivity and adverse events remain urgent issues. The key to promoting the development of EC immunotherapy is to select the best patients according to the molecular classification and immunophenotype such as tumor mutation load, MMR status, pd-l1 expression, tumor infiltrating immune cells to truly achieve accurate and personalized treatment. More new and influential EC immunotherapies, such as adoptive cell immunotherapy, still need to be explored in future clinical practice.

Phenotypic characteristics of taurodontism and a novel WNT10A variant in non-syndromic oligodontia family.

OBJECTIVE: Variants in wingless-type MMTV integration site family member 10A (WNT10A) have been proposed to be the most common cause of non-syndromic oligodontia (NSO). The goal of the present study was to identify the novel WNT10A variants in Chinese families with NSO. DESIGN: Clinical data were collected from 39 families with oligodontia admitted to the Hospital of Stomatology Hebei Medical University (China) from 2016 to 2022. Whole-exome sequencing (WES) and Sanger sequencing were performed to identify WNT10A variants in three families with non-syndromic oligodontia. Amino acid conservation analysis and protein conformational analysis were conducted for the WNT10A variant. Genotype-phenotype analysis was performed on the previously reported WNT10A variants related to NSO. RESULTS: We found a novel heterozygous WNT10A variant c.1127 G>A (p.Cys376Tyr) and two reported heterozygous variants c.460 C>A (p.Leu154Met) and c.511 C>T (p.Arg171Cys). Structural modeling showed that the novel WNT10A variant was located in a highly conserved domain, which led to structural damage of WNT10A protein. In addition, we found that the phenotype of the WNT10A variants affected the maxillary second premolars, followed by the mandibular second premolars, and rarely affected the maxillary central incisor. Herein, it is the first time to report that NSO patients with WNT10A monoallele mutation carry taurodontism phenotype and 6.1% prevalence of taurodontism in WNT10A-related NSO patients. CONCLUSIONS: Our results demonstrated that the novel variant c.1127 G>A (p.Cys376Tyr) of WNT10A causes NSO. The present study expanded the known variation spectrum of WNT10A and provided valuable information for genetic counseling of families.

In silico identification of natural compounds against SARS-CoV-2 main protease from Chinese herbal medicines.

Aims: To determine natural compounds with inhibitory effects toward SARS-CoV-2 Mpro from Chinese herbal medicines. Materials & methods: ∼1200 natural compounds from 19 Chinese herbal medicines were collected. Computational methods including molecular docking, drug-likeness assessment, molecular dynamics simulation and molecular mechanics Poisson-Boltzmann surface area analysis were combined to obtain potent inhibitors against SARS-CoV-2 Mpro. Results: Top 20 compounds mainly originated from Ranunculus ternatus and Picrasma quassioides exhibited low binding free energies which below -9.0 kcal/mol. Compounds Japonicone G and Picrasidine T were obtained with favorable drug-likeness. Moreover, the complex of Japonicone G and Mpro had prominent stability. Conclusion: Natural compound Japonicone G is highly promising as a potent inhibitor against SARS-CoV-2 for further study.