Anchored Cobalt Nanoparticles on Layered Perovskites for Rapid Peroxymonosulfate Activation in Antibiotic Degradation.

In the Fenton-like reaction, revealing the dynamic evolution of the active sites is crucial to achieve the activity improvement and stability of the catalyst. This study reports a perovskite oxide in which atomic (Co0) in situ embedded exsolution occurs during the high-temperature phase transition. This unique anchoring strategy significantly improves the Co3+/Co2+ cycling efficiency at the interface and inhibits metal leaching during peroxymonosulfate (PMS) activation. The Co@L-PBMC catalyst exhibits superior PMS activation ability and could achieve 99% degradation of tetracycline within 5 min. The combination of experimental characterization and density functional theory (DFT) calculations elucidates that the electron-deficient oxygen vacancy accepts an electron from the Co 3d-orbital, resulting in a significant electron delocalization of the Co site, thereby facilitating the adsorption of the *HSO5/*OH intermediate onto the "metal-VO bridge" structure. This work provides insights into the PMS activation mechanism at the atomic level, which will guide the rational design of next-generation catalysts for environmental remediation.

Downregulation of lncRNA CDKN2B-AS1 attenuates inflammatory response in mice with allergic rhinitis by regulating miR-98-5p/SOCS1 axis.

Long non-coding RNA cyclin-dependent kinase inhibitor 2B antisense RNA 1 (CDKN2B-AS1) in various diseases has been verified. However, the underlying mechanism of CDKN2B-AS1 contributes to the development of allergic rhinitis (AR) remains unknown. To evaluate the impact of CDKN2B-AS1 on AR, BALB/c mice were sensitized by intraperitoneal injection of normal saline containing ovalbumin (OVA) and calmogastrin to establish an AR model. Nasal rubbing and sneezing were documented after the final OVA treatment. The concentrations of IgE, IgG1, and inflammatory elements were quantified using ELISA. Hematoxylin and eosin (H&E) staining and immunofluorescence were used to assess histopathological variations and tryptase expression, respectively. StarBase, TargetScan and luciferase reporter assays were applied to predict and confirm the interactions among CDKN2B-AS1, miR-98-5p, and SOCS1. CDKN2B-AS1, miR-98-5p, and SOCS1 levels were assessed by quantitative real-time PCR (qRT-PCR) or western blotting. Our results revealed that CDKN2B-AS1 was obviously over-expressed in the nasal mucosa of AR patients and AR mice. Down-regulation of CDKN2B-AS1 significantly decreased nasal rubbing and sneezing frequencies, IgE and IgG1 concentrations, and cytokine levels. Furthermore, down-regulation of CDKN2B-AS1 also relieved the pathological changes in the nasal mucosa, and the infiltration of eosinophils and mast cells. Importantly, these results were reversed by the miR-98-5p inhibitor, whereas miR-98-5p directly targeted CDKN2B-AS1, and miR-98-5p negatively regulated SOCS1 level. Our findings demonstrate that down-regulation of CDKN2B-AS1 improves allergic inflammation and symptoms in a murine model of AR through the miR-98-5p/SOCS1 axis, which provides new insights into the latent functions of CDKN2B-AS1 in AR treatment.

H3K27ac modification and transcription characteristics of adipose and muscle tissues in Chuxiang Black pig.

The establishment of high-quality pork breeds for improving meat quality in the pig industry is needed. The Chuxiang Black (CX) pig is a new breed developed from Chinese local pigs and Western lean pigs that has a high proportion of lean meat and excellent meat quality. However, the characteristics of cis-regulatory elements in CX pigs are still unknown. In this study, cis-regulatory elements of muscle and adipose tissues in CX pigs were investigated using ChIP-seq and RNA sequencing. Compared with the reported cis-regulatory elements of muscle and adipose tissues, 1768 and 1012 highly activated enhancers and 433 and 275 highly activated promoters in CX muscle and adipose tissues were identified, respectively. Motif analysis showed that transcription factors, such as MEF2A and MEF2C, were core regulators of highly activated enhancers and promoters in muscle. Similarly, the transcription factors JUNB and CUX1 were identified as essential for highly activated enhancers and promoters in CX adipose tissue. These results enrich the resources for the analysis of cis-regulatory elements in the pig genome and provide new basic data for further meat quality improvement through breeding in pigs.

Downregulation of Roundabout guidance receptor 2 suppresses hepatocellular carcinoma progression by interacting with Y-box binding protein 1.

Roundabout guidance receptor 2 (Robo2) is closely related to malignant tumors such as pancreatic cancer and liver fibrosis, but there is no relevant research on the role of Robo2 in HCC. The study will further explore the function and mechanism of Robo2 and its downstream target genes in HCC. Firstly, Robo2 protein levels in human HCC tissues and paired adjacent normal liver tissues were detected. Then we established HepG2 and Huh7 hepatoma cell lines with knock-down Robo2 by transfection with lentiviral vectors, and examined the occurrence of EMT, proliferation and apoptosis abilities in HCC cells by western blot, flow cytometry, wound healing assay and TUNEL staining. Then we verified the interaction between Robo2 and its target gene by Co-IP and immunofluorescence co-staining, and further explored the mechanism of Robo2 and YB-1 by rescue study. The protein expression level of Robo2 in HCC was considerably higher than that in the normal liver tissues. After successfully constructing hepatoma cells with knock-down Robo2, it was confirmed that down-regulated Robo2 suppressed EMT and proliferation of hepatoma cells, and accelerated the cell apoptosis. High-throughput sequencing and validation experiments verified that YB-1 was the downstream target gene of Robo2, and over-expression of YB-1 could reverse the apoptosis induced by Robo2 down-regulation and its inhibitory effect on EMT and proliferation. Robo2 deficiency inhibits EMT and proliferation of hepatoma cells and augments the cell apoptosis by regulating YB-1, thus inhibits the occurrence of HCC and provides a new strategy for the treatment of HCC.

SPOP regulates the expression profiles and alternative splicing events in human hepatocytes.

Speckle type BTB/POZ protein (SPOP) may have cancer promoting or inhibiting effects. At present, the role of SPOP in hepatocellular carcinoma (HCC) has rarely been studied. In this study, to investigate the effects of SPOP in HCC and elucidate the underlying molecular mechanisms of its relationship with genes, differentially expressed genes (DEGs) were classified through RNA sequencing. The gene ontology analysis and Kyoto Encyclopedia of Genes and Genomes functional pathway analysis were used to further predict the function of DEGs after the overexpression of SPOP. The biological function of SPOP-regulated alternative splicing events in cells is comprehensively assessed. The Cancer Genome Atlas database and Gene Expression Omnibus dataset were performed to evaluate the correlation between SPOP and HCC progression. Due to SPOP overexpression, 56 DEGs in the HCC related pathway were further identified. The results showed that SPOP overexpression facilitated the cell proliferation and changed the gene expression profiles of human normal hepatocytes. SPOP-regulated alternative splicing events were involved in pathways associated with cellular processes, metabolism, environmental information procession, organismal systems, and so on. In conclusion, SPOP may potentially exhibit tumor-promoting effects, necessitating further investigations to unveil its molecular mechanisms comprehensively.

[Clinical and genetic analyses of Joubert syndrome in children]. / 儿童Joubertç»¼åˆå¾ä¸´åºŠåŠé—ä¼ å­¦åˆ†æž.

OBJECTIVES: To study the clinical and genetic features of Joubert syndrome (JS) in children. METHODS: A retrospective analysis was performed on the clinical data, genetic data, and follow-up data of 20 children who were diagnosed with JS in the Department of Children's Rehabilitation, the Third Affiliated Hospital of Zhengzhou University, from January 2017 to July 2022. RESULTS: Among the 20 children with JS, there were 11 boys and 9 girls. The common clinical manifestations were developmental delay (20 children, 100%), abnormal eye movement (19 children, 95%), and hypotonia (16 children, 80%), followed by abnormal respiratory rhythm in 5 children (25%) and unusual facies (including prominent forehead, low-set ears, and triangular mouth) in 3 children (15%), and no limb deformity was observed. All 20 children (100%) had the typical "molar tooth sign" and "midline cleft syndrome" on head images, and 6 children (30%) had abnormal eye examination results. Genetic testing was performed on 7 children and revealed 6 pathogenic genes, i.e., the CPLANE1, RPGRIP1L, MKS1, CC2D2A, CEP120, and AHI1 genes. CONCLUSIONS: For children with developmental delay, especially those with abnormal eye movement and hypotonia, it is recommended to perform a head imaging examination to determine the presence or absence of "molar tooth sign" and "midline cleft syndrome", so as to screen for JS to avoid missed diagnosis and misdiagnosis. There are many pathogenic genes for JS, and whole-exome sequencing can assist in the diagnosis of JS.

Effects of OsAOX1a Deficiency on Mitochondrial Metabolism at Critical Node of Seed Viability in Rice.

Mitochondrial alternative oxidase 1a (AOX1a) plays an extremely important role in the critical node of seed viability during storage. However, the regulatory mechanism is still poorly understood. The aim of this study was to identify the regulatory mechanisms by comparing OsAOX1a-RNAi and wild-type (WT) rice seed during artificial aging treatment. Weight gain and time for the seed germination percentage decreased to 50% (P50) in OsAOX1a-RNAi rice seed, indicating possible impairment in seed development and storability. Compared to WT seeds at 100%, 90%, 80%, and 70% germination, the NADH- and succinate-dependent O2 consumption, the activity of mitochondrial malate dehydrogenase, and ATP contents all decreased in the OsAOX1a-RNAi seeds, indicating that mitochondrial status in the OsAOX1a-RNAi seeds after imbibition was weaker than in the WT seeds. In addition, the reduction in the abundance of Complex I subunits showed that the capacity of the mitochondrial electron transfer chain was significantly inhibited in the OsAOX1a-RNAi seeds at the critical node of seed viability. The results indicate that ATP production was impaired in the OsAOX1a-RNAi seeds during aging. Therefore, we conclude that mitochondrial metabolism and alternative pathways were severely inhibited in the OsAOX1a-RNAi seeds at critical node of viability, which could accelerate the collapse of seed viability. The precise regulatory mechanism of the alternative pathway at the critical node of viability needs to be further analyzed. This finding might provide the basis for developing monitoring and warning indicators when seed viability declines to the critical node during storage.

Integrated analysis of genome-wide association studies and 3D epigenomic characteristics reveal the BMP2 gene regulating loin muscle depth in Yorkshire pigs.

BACKGROUND: The lack of integrated analysis of genome-wide association studies (GWAS) and 3D epigenomics restricts a deep understanding of the genetic mechanisms of meat-related traits. With the application of techniques as ChIP-seq and Hi-C, the annotations of cis-regulatory elements in the pig genome have been established, which offers a new opportunity to elucidate the genetic mechanisms and identify major genetic variants and candidate genes that are significantly associated with important economic traits. Among these traits, loin muscle depth (LMD) is an important one as it impacts the lean meat content. In this study, we integrated cis-regulatory elements and genome-wide association studies (GWAS) to identify candidate genes and genetic variants regulating LMD. RESULTS: Five single nucleotide polymorphisms (SNPs) located on porcine chromosome 17 were significantly associated with LMD in Yorkshire pigs. A 10 kb quantitative trait locus (QTL) was identified as a candidate functional genomic region through the integration of linkage disequilibrium and linkage analysis (LDLA) and high-throughput chromosome conformation capture (Hi-C) analysis. The BMP2 gene was identified as a candidate gene for LMD based on the integrated results of GWAS, Hi-C meta-analysis, and cis-regulatory element data. The identified QTL region was further verified through target region sequencing. Furthermore, through using dual-luciferase assays and electrophoretic mobility shift assays (EMSA), two SNPs, including SNP rs321846600, located in the enhancer region, and SNP rs1111440035, located in the promoter region, were identified as candidate SNPs that may be functionally related to the LMD. CONCLUSIONS: Based on the results of GWAS, Hi-C, and cis-regulatory elements, the BMP2 gene was identified as an important candidate gene regulating variation in LMD. The SNPs rs321846600 and rs1111440035 were identified as candidate SNPs that are functionally related to the LMD of Yorkshire pigs. Our results shed light on the advantages of integrating GWAS with 3D epigenomics in identifying candidate genes for quantitative traits. This study is a pioneering work for the identification of candidate genes and related genetic variants regulating one key production trait (LMD) in pigs by integrating genome-wide association studies and 3D epigenomics.

Facet Engineering-Induced Construction of Ni2P/ZnIn2S4 Heterostructures for Boosted Photocatalytic CO2 Reduction.

Facet engineering was realized to enhance the CO2 photoreduction performance of the Ni2P/ZnIn2S4 heterostructure, in which the commonly exposed (1 0 2) face of ZnIn2S4 was converted to the (1 0 1) face due to the unique properties of the phosphide. The variation in the crystal plane strengthened the intense interfacial contact between Ni2P and ZnIn2S4, resulting in the promotion of utilization and absorption efficiency for incident light and boosting the surface reaction rate. Combined with the significant metallicity of Ni2P, inhibited recombination and strengthened transfer efficiency were achieved, leading to an obvious enhancement of photoreduction activity over Ni2P/ZnIn2S4 compared to pure samples. In particular, the optimal NZ7 composite (the mass ratio of Ni2P to ZnIn2S4) reached 68.31 µmol h-1 g-1 of CH4, 10.65 µmol h-1 g-1 of CH3OH, and 11.15 µmol h-1 g-1 of HCOOH. The mechanism of the CO2 photoreduction process was elucidated using ESR and in situ DRIFTS techniques.

The enormous repetitive Antarctic krill genome reveals environmental adaptations and population insights.

Antarctic krill (Euphausia superba) is Earth's most abundant wild animal, and its enormous biomass is vital to the Southern Ocean ecosystem. Here, we report a 48.01-Gb chromosome-level Antarctic krill genome, whose large genome size appears to have resulted from inter-genic transposable element expansions. Our assembly reveals the molecular architecture of the Antarctic krill circadian clock and uncovers expanded gene families associated with molting and energy metabolism, providing insights into adaptations to the cold and highly seasonal Antarctic environment. Population-level genome re-sequencing from four geographical sites around the Antarctic continent reveals no clear population structure but highlights natural selection associated with environmental variables. An apparent drastic reduction in krill population size 10 mya and a subsequent rebound 100 thousand years ago coincides with climate change events. Our findings uncover the genomic basis of Antarctic krill adaptations to the Southern Ocean and provide valuable resources for future Antarctic research.

Copper-Based Catalysts for Electrochemical Reduction of Carbon Dioxide to Ethylene.

Electrochemical reduction of CO2 into high energy density multi-carbon chemicals or fuels (e. g., ethylene) via new renewable energy storage has extraordinary implications for carbon neutrality. Copper (Cu)-based catalysts have been recognized as the most promising catalysts for the electrochemical reduction of CO2 to ethylene (C2 H4 ) due to their moderate CO adsorption energy and moderate hydrogen precipitation potential. However, the poor selectivity, low current density and high overpotential of the CO2 RR into C2 H4 greatly limit its industrial applications. Meanwhile, the complex reaction mechanism is still unclear, which leads to blindness in the design of catalysts. Herein, we systematically summarized the latest research, proposed possible conversion mechanisms and categorized the general strategies to adjust of the structure and composition for CO2 RR, such as tip effect, defect engineering, crystal plane catalysis, synergistic effect, nanoconfinement effect and so on. Eventually, we provided a prospect of the future challenges for further development and progress in CO2 RR. Previous reviews have summarized catalyst designs for the reduction of CO2 to multi-carbon products, while lacking in targeting C2 H4 alone, an important industrial feedstock. This Review mainly aims to provide a comprehensive understanding for the design strategies and challenges of electrocatalytic CO2 reduction to C2 H4 through recent researches and further propose some guidelines for the future design of copper-based catalysts for electroreduction of CO2 to C2 H4 .

IAnimal: a cross-species omics knowledgebase for animals.

With the exponential growth of multi-omics data, its integration and utilization have brought unprecedented opportunities for the interpretation of gene regulation mechanisms and the comprehensive analyses of biological systems. IAnimal (https://ianimal.pro/), a cross-species, multi-omics knowledgebase, was developed to improve the utilization of massive public data and simplify the integration of multi-omics information to mine the genetic mechanisms of objective traits. Currently, IAnimal provides 61 191 individual omics data of genome (WGS), transcriptome (RNA-Seq), epigenome (ChIP-Seq, ATAC-Seq) and genome annotation information for 21 species, such as mice, pigs, cattle, chickens, and macaques. The scale of its total clean data has reached 846.46 TB. To better understand the biological significance of omics information, a deep learning model for IAnimal was built based on BioBERT and AutoNER to mine 'gene' and 'trait' entities from 2 794 237 abstracts, which has practical significance for comprehending how each omics layer regulates genes to affect traits. By means of user-friendly web interfaces, flexible data application programming interfaces, and abundant functional modules, IAnimal enables users to easily query, mine, and visualize characteristics in various omics, and to infer how genes play biological roles under the influence of various omics layers.

Numerical study of hydrodynamic effects on Manila clam population distribution and transport in the Southwest Laizhou Bay, China.

Pelagic larvae of marine organisms are abundant on many continental shelves. Due to their importance as a biological resource and contribution to marine biodiversity, the dynamics of pelagic larvae have received wide attention. Numerical models are an efficient approach to assessing pelagic larval transport driven by various ocean dynamics. However, few studies have focused on the pelagic larval distribution of Manila clam populations and related dynamic factors in the southwestern Laizhou Bay (SLB) during late spring. A hydrodynamic model including realistic meteorologic and oceanic boundary conditions was coupled with a larval transport model to describe the pelagic larval distribution and transport processes. The hydrodynamic model was validated with observational and satellite-derived data. Effects of hydrodynamics and biological behavior on pelagic dynamics were further simulated with numerical experiments. During the early planktonic period, most clam larvae in the SLB were transported eastward or northeastward. Two potential larval settlement areas (LSAs) were recognized: the east side of the dike outside Guangli port and the Lao River estuary. The dominant controlling factor was southerly wind, and larvae's response to river plume or estuarine circulation played a secondary role. Larval transport depended on bottom subtidal currents when late-stage larvae settled near the bottom layer. The hydrodynamic and larval transport model established in this study can be applied to other bays and coastal waters. Understanding the clam larval distribution and transport dynamics in the SLB can provide a reference for predicting LSAs and biological resource management in coastal aquaculture areas.

USF1-CHCHD4 axis promotes lung adenocarcinoma progression partially via activating the MYC pathway.

BACKGROUND: This study aimed to identify genes related to lung adenocarcinoma (LUAD) and investigate the effects and molecular mechanisms of coiled-coil-helix-coiled-coil-helix domain containing 4 (CHCHD4) in the progression of LUAD. METHODS: The GEPIA database was used to evaluate the differential expression of CHCHD4 and the survival data of LUAD patients compared to controls. TCGA-LUAD database, JASPAR website, and GSEA were used to analyse the relationship between CHCHD4 and the upstream stimulating factor 1 (USF1) or MYC pathways. The proliferation, apoptosis, migration, and invasion of LUAD cells were evaluated using cell counting kit-8, 5-ethynyl-2'-deoxyuridine, colony formation, flow cytometry, wound healing, and transwell assays. qRT-PCR, western blotting, and immunohistochemistry were used to detect the mRNA and protein expression, respectively. Furthermore, xenograft tumours from nude mice were used to verify the effect of CHCHD4 on LUAD in vivo. RESULTS: CHCHD4 overexpression was found in LUAD tumor tissues and cells, and high CHCHD4 was associated with a poor prognosis. Interestingly, CHCHD4 knockdown suppressed the malignant phenotype of the LUAD cells. Moreover, we found that USF1 upregulated CHCHD4 and promoted LUAD progression. CHCHD4 knockdown also inhibited the progression of LUAD. In addition, CHCHD4 knockdown suppressed xenograft tumour growth. CONCLUSION: USF1-CHCHD4 axis can promote LUAD progress, which may be through activating MYC pathway.

Melatonin enhances autologous adipose-derived stem cells to improve mouse ovarian function in relation to the SIRT6/NF-κB pathway.

BACKGROUND: Premature ovarian insufficiency (POI) is the main cause of female infertility. Adipose-derived stem cells (ADSCs) are ideal candidates for the treatment of POI. However, some deficient biological characteristics of ADSCs limit their utility. This study investigated whether melatonin (MLT)-pretreated autologous ADSCs were superior to ADSCs alone in the treatment of the POI mouse model. METHODS: Autologous ADSCs were isolated and cultured in MLT-containing medium. Surface markers of ADSCs were detected by flow cytometry. To determine the effect of MLT on ADSCs, CCK-8 assay was used to detect ADSCs proliferation and enzyme-linked immunosorbent assay (ELISA) was used to detect the secretion of cytokines. The POI model was established by intraperitoneal injection of cyclophosphamide and busulfan. Then, MLT-pretreated autologous ADSCs were transplanted into mice by intraovarian injection. After 7 days of treatment, ovarian morphology, follicle counts, and sex hormones levels were evaluated by hematoxylin and eosin (H&E) staining and ELISA, and the recovery of fertility was also observed. The expressions of SIRT6 and NF-κB were detected by immunohistochemical (IHC) staining and quantitative real-time polymerase chain reaction (qRT-PCR). RESULTS: Flow cytometry showed that autologous ADSCs expressed CD90 (99.7%) and CD29 (97.5%). MLT can not only promote the proliferation of ADSCs but also boost their secretory function, especially when ADSCs were pretreated with 5 µM MLT for 3 days, improving the interference effect. After transplantation of autologous ADSCs pretreated with 5 µM MLT, the serum hormone levels and reproductive function were significantly recovered, and the mean counts of primordial follicle increased. At the same time, the expression of SIRT6 was remarkably increased and the expression of NF-κB was significantly decreased in this group. CONCLUSIONS: MLT enhances several effects of ADSCs in restoring hormone levels, mean primordial follicle counts, and reproductive capacity in POI mice. Meanwhile, our results suggest that the SIRT6/NF-κB signal pathway may be the potential therapeutic mechanism for ADSCs to treat POI.

Enhancer-promoter interaction maps provide insights into skeletal muscle-related traits in pig genome.

BACKGROUND: Gene expression programs are intimately linked to the interplay of active cis regulatory elements mediated by chromatin contacts and associated RNAs. Genome-wide association studies (GWAS) have identified many variants in these regulatory elements that can contribute to phenotypic diversity. However, the functional interpretation of these variants remains nontrivial due to the lack of chromatin contact information or limited contact resolution. Furthermore, the distribution and role of chromatin-associated RNAs in gene expression and chromatin conformation remain poorly understood. To address this, we first present a comprehensive interaction map of nuclear dynamics of 3D chromatin-chromatin interactions (H3K27ac BL-HiChIP) and RNA-chromatin interactions (GRID-seq) to reveal genomic variants that contribute to complex skeletal muscle traits. RESULTS: In a genome-wide scan, we provide systematic fine mapping and gene prioritization from GWAS leading signals that underlie phenotypic variability of growth rate, meat quality, and carcass performance. A set of candidate functional variants and 54 target genes previously not detected were identified, with 71% of these candidate functional variants choosing to skip over their nearest gene to regulate the target gene in a long-range manner. The effects of three functional variants regulating KLF6 (related to days to 100 kg), MXRA8 (related to lean meat percentage), and TAF11 (related to loin muscle depth) were observed in two pig populations. Moreover, we find that this multi-omics interaction map consists of functional communities that are enriched in specific biological functions, and GWAS target genes can serve as core genes for exploring peripheral trait-relevant genes. CONCLUSIONS: Our results provide a valuable resource of candidate functional variants for complex skeletal muscle-related traits and establish an integrated approach to complement existing 3D genomics by exploiting RNA-chromatin and chromatin-chromatin interactions for future association studies.

Proteomic analysis of differential anther development from sterile/fertile lines in Capsicum annuum L.

Background: Pepper (Capsicum annuum L.) is a major cash crop throughout the world. Male sterility is an important characteristic in crop species that leads to a failure to produce functional pollen, and it has crucial roles in agricultural breeding and the utilization of heterosis. Objectives: In this study, we identified many crucial factors and important components in metabolic pathways in anther and pollen development, and elucidated the molecular mechanism related to pollen abortion in pepper. Methods: Pepper pollen was observed at different stages to detect the characteristics associated with male sterility and fertility. The phytohormone and oxidoreductase activities were detected in spectrophotometric and redox reaction assays, respectively. Proteins were extracted from male sterile and fertile pepper lines, and identified by TMT/iTRAQ (tandem mass tags/isobaric tags for relative and absolute quantitation) and LC-MS/MS (liquid chromatograph-mass spectrometer) analysis. Differentially abundant proteins (DAPs) were analyzed based on Gene Ontology annotations and the Kyoto Encyclopedia of Genes and Genomes database according to |fold change)| > 1.3 and P value < 0.05. DAPs were quantified in the meiosis, tetrad, and binucleate stages by parallel reaction monitoring (PRM). Results: In this study, we screened and identified one male sterile pepper line with abnormal cytological characteristics in terms of pollen development. The peroxidase and catalase enzyme activities were significantly reduced and increased, respectively, in the male sterile line compared with the male fertile line. Phytohormone analysis demonstrated that the gibberellin, jasmonic acid, and auxin contents changed by different extents in the male sterile pepper line. Proteome analysis screened 1,645 DAPs in six clusters, which were mainly associated with the chloroplast and cytoplasm based on their similar expression levels. According to proteome analysis, 45 DAPs were quantitatively identified in the meiosis, tetrad, and binucleate stages by PRM, which were related to monoterpenoid biosynthesis, and starch and sucrose metabolism pathways. Conclusions: We screened 1,645 DAPs by proteomic analysis and 45 DAPs were related to anther and pollen development in a male sterile pepper line. In addition, the activities of peroxidase and catalase as well as the abundances of phytohormones such as gibberellin, jasmonic acid, and auxin were related to male sterility. The results obtained in this study provide insights into the molecular mechanism responsible for male sterility and fertility in pepper.

Effectiveness and Safety of Anlotinib with or without PD-1 Blockades in the Treatment of Patients with Advanced Primary Hepatocellular Carcinoma: A Retrospective, Real-World Study in China.

Purpose: Anlotinib, a novel multi-target tyrosine kinase inhibitor, has shown encouraging antitumor effects in advanced hepatocellular carcinoma (HCC). This study evaluated the effectiveness and safety of anlotinib with or without programmed death-1 (PD-1) blockades for patients with advanced primary HCC in a real-world setting in China. Patients and Methods: Between July 2019 and May 2021, 27 patients with advanced primary HCC who received at least 2 cycles of anlotinib were included in this retrospective study. Primary endpoint was objective response rate (ORR). Secondary endpoints were disease control rate (DCR), progression-free survival (PFS), overall survival (OS), and safety. Results: Of the 27 patients, ORR and DCR were 25.93% and 74.07%, respectively. The median follow-up time was 6.27 months (range: 1.30-17.40) with a median PFS and OS of 3.29 months (95% CI: 1.31-15.47) and 6.21 months (95% CI: 2.23-15.87), respectively. A total of 14 patients received anlotinib and PD-1 blockade combination therapy, and 13 received anlotinib monotherapy. No significant differences were observed in ORR (28.57 vs 23.08%), DCR (71.43 vs 76.92%), PFS (3.38 [95% CI: 2.66-13.14] vs 11.86 months [95% CI: 4.27-15.93]) and OS (4.90 [95% CI: 2.56-13.60] vs 11.04 months [95% CI: 1.31-17.18]) between the two groups (all p>0.05). Treatment-related AEs were reported in 88.89% of patients. Grade 3 AE was bleeding, which occurred in 3 patients (11.11%). Conclusion: Anlotinib yielded a promising efficacy and manageable safety in patients with advanced primary HCC irrespective of whether patients received PD-1 blockades, indicating that anlotinib might be a promising treatment option for this patient population.