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The plant cuticle, a structure primarily composed of wax and cutin, forms a continuous coating over most aerial plant surfaces. The cuticle plays important roles in plant tolerance to environmental stress, including stress imposed by drought. Some members of the 3-KETOACYL-COA SYNTHASE (KCS) family are known to act as metabolic enzymes involved in cuticular wax production. Here we report that Arabidopsis (Arabidopsis thaliana) KCS3, which was previously shown to lack canonical catalytic activity, instead functions as a negative regulator of wax metabolism by reducing the enzymatic activity of KCS6, a key KCS involved in wax production. We demonstrate that the role of KCS3 in regulating KCS6 activity involves physical interactions between specific subunits of the fatty acid elongation complex and is essential for maintaining wax homeostasis. We also show that the role of the KCS3–KCS6 module in regulating wax synthesis is highly conserved across diverse plant taxa from Arabidopsis to the moss Physcomitrium patens, pointing to a critical ancient and basal function of this module in finely regulating wax synthesis.

The chemical reaction pathway and growth process of Ga2O3 grown via TEGa and H2O/O2/N2O in MOCVD were investigated.

This study aimed to build a comprehensive model for predicting the overall survival (OS) of cervical cancer patients who received standard treatments and to build a series of new stages based on the International Federation of Gynecologists and Obstetricians (FIGO) stages for better such predictions. We collected the cervical cancer patients diagnosed since the year 2000 from the Surveillance, Epidemiology, and End Results (SEER) database. Cervical cancer patients who received radiotherapy or surgery were included. Log-rank tests and Cox regression were used to identify potential factors of OS. Bayesian networks (BNs) were built to predict 3- and 5-year survival. We also grouped the patients into new stages by clustering their 5-year survival probabilities based on FIGO stage, age, and tumor differentiation. Cox regression suggested black ethnicity, adenocarcinoma, and single status as risks for poorer prognosis, in addition to age and stage. A total of 43,749 and 39,333 cases were finally eligible for the 3- and 5-year BNs, respectively, with 11 variables included. Cluster analysis and Kaplan-Meier curves indicated that it was best to divide the patients into nine modified stages. The BNs had excellent performance, with area under the curve and maximum accuracy of 0.855 and 0.804 for 3-year survival, and 0.851 and 0.787 for 5-year survival, respectively. Thus, BNs are excellent candidates for predicting cervical cancer survival. It is necessary to consider age and tumor differentiation when estimating the prognosis of cervical cancer using FIGO stages.

Background. Ovarian cancer (OC) is one of the most frequently seen and fatal gynecological malignancies, and oxidative stress (OS) plays a critical role in the development and chemoresistance of OC. Materials and Methods. OS-related genes (OSRGs) were obtained from the Molecular Signatures Database. Besides, gene expression profiles and clinical information from The Cancer Genome Atlas (TCGA) were selected to identify the prognostic OSRGs. Moreover, univariate Cox regression, LASSO, and multivariate Cox regression analyses were conducted sequentially to establish a prognostic signature, which was later validated in three independent Gene Expression Omnibus (GEO) datasets. Next, gene set enrichment analysis (GSEA) and tumor mutation burden (TMB) analysis were performed. Afterwards, immune checkpoint genes (ICGs) and the tumor immune dysfunction and exclusion (TIDE) algorithm, together with IMvigor210 and GSE78220 cohorts, were applied to comprehensively explore the role of OSRG signature in immunotherapy. Further, the CellMiner and Genomics of Drug Sensitivity in Cancer (GDSC) databases were also applied in investigating the significance of OSRG signature in chemotherapy. Results. Altogether, 34 prognostic OSRGs were identified, among which 14 were chosen to establish the most valuable prognostic signature. The Kaplan-Meier (KM) analysis suggested that patients with lower OS-related risk score had better prognosis. The area under the curve (AUC) values were 0.71, 0.76, and 0.85 in 3, 5, and 7 years separately, and the stability of this prognostic signature was confirmed in three GEO datasets. As revealed by GSEA and TMB analysis results, OC patients in low-risk group might have better immunotherapeutic response, which was consistent with ICG expression and TIDE analyses. Moreover, both IMvigor210 and GSE78220 cohorts demonstrated that patients with lower OS-related risk score were more likely to benefit from anti-PD-1/L1 immunotherapy. In addition, the association between prognostic signature and drug sensitivity was explored. Conclusion. According to our results in this work, OSRG signature can act as a powerful prognostic predictor for OC, which contributes to generating more individualized therapeutic strategies for OC patients.

Antibody therapeutics and vaccines for coronavirus disease 2019 (COVID-19) have been approved in many countries, with most being developed based on the original strain of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). SARS-CoV-2 has an exceptional ability to mutate under the pressure of host immunity, especially the immune-dominant spike protein of the virus, which is the target of both antibody drugs and vaccines. Given the continuous evolution of the virus and the identification of critical mutation sites, the World Health Organization (WHO) has named 5 variants of concern (VOCs): 4 are previously circulating VOCs, and 1 is currently circulating (Omicron). Due to multiple mutations in the spike protein, the recently emerged Omicron and descendent lineages have been shown to have the strongest ability to evade the neutralizing antibody (NAb) effects of current antibody drugs and vaccines. The development and characterization of broadly neutralizing antibodies (bNAbs) will provide broad strategies for the control of the sophisticated virus SARS-CoV-2. In this review, we describe how the virus evolves to escape NAbs and the potential neutralization mechanisms that associated with bNAbs. We also summarize progress in the development of bNAbs against SARS-CoV-2, human coronaviruses (CoVs) and other emerging pathogens and highlight their scientific and clinical significance.

RNA C-to-U editing in organelles is essential for plant growth and development; however, the underlying mechanism is not fully understood. Here, we report that pentatricopeptide repeat (PPR)-E subclass proteins carry out RNA C-to-U editing by recruiting the trans deaminase PPR motifs, coiled-coil, and DYW domain-containing protein 1 (PCW1) in maize (Zea mays) mitochondria. Loss-of-function of bZIP and coiled-coil domain-containing PPR 1 (bCCP1) or PCW1 arrests seed development in maize. bCCP1 encodes a bZIP and coiled-coil domain-containing PPR protein, and PCW1 encodes an atypical PPR–DYW protein. bCCP1 is required for editing at 66 sites in mitochondria and PCW1 is required for editing at 102 sites, including the 66 sites that require bCCP1. The PCW1-mediated editing sites are exclusively associated with PPR-E proteins. bCCP1 interacts with PCW1 and the PPR-E protein Empty pericarp7 (EMP7). Two multiple organellar RNA editing factor (MORF) proteins, ZmMORF1 and ZmMORF8, interact with PCW1, EMP7, and bCCP1. ZmMORF8 enhanced the EMP7–PCW1 interaction in a yeast three-hybrid assay. C-to-U editing at the ccmFN-1553 site in maize required EMP7, bCCP1, and PCW1. These results suggest that PPR-E proteins function in RNA editing by recruiting the trans deaminase PCW1 and bCCP1, and MORF1/8 assist this recruitment through protein–protein interactions.

Sustainable urban forms (SUF) guide spatial creation, significantly revitalise the development of traditional settlements, and are an essential theoretical support for urban design. At the same time, the emergence of quantitative spatial analysis technology further promotes the visualised evaluation of the performance of spatial vitality in urban design. However, current research rarely studies the spatial vitality of traditional settlements with quantitative spatial analysis from the SUF perspective. Therefore, this research takes Anren Ancient Town in Chengdu, Western China, as an example to propose a design based on sustainable urban form theory to raise local spatial vitality. Then, it introduces the vitality evaluation system based on the urban form index (UFI) with three measurement methods: Space Syntax, Spacemate, and MXI, and conducts a comparative spatial vitality evaluation of Anren Ancient Town’s status quo to explain the process of how the design scheme came about. The results found that urban design proposals based on the principles of compactness, mixed land use and diversity in SUF design guidelines can effectively improve the vitality of traditional settlements. The high vitality of an urban settlement could be achieved by combining SUF-based design guidelines and UFI-based evaluation systems. The spatial vitality evaluation system based on the SUF could assist and optimise decision-making in design and act as a paradigm for urban design or urban regeneration in traditional towns.

Despite the need in various applications, accurate quantification of nucleic acids still remains a challenge. The widely-used qPCR has reduced accuracy at ultralow template concentration and is susceptible to nonspecific amplifications. The more recently developed dPCR is costly and cannot handle high-concentration samples. We combine the strengths of qPCR and dPCR by performing PCR in silicon-based microfluidic chips and demonstrate high quantification accuracy in a large concentration range. Importantly, at low template concentration, we observe on-site PCR (osPCR), where only certain sites of the channel show amplification. The sites have almost identical ct values, showing osPCR is a quasi-single molecule phenomenon. Using osPCR, we can measure both the ct values and the absolute concentration of templates in the same reaction. Additionally, osPCR enables identification of each template molecule, allowing removal of nonspecific amplification during quantification and greatly improving quantification accuracy. We develop sectioning algorithm that improves the signal amplitude and demonstrate improved detection of COVID in patient samples.

Background Meiotic recombination is initiated by Spo11-dependent programmed DNA double-strand breaks (DSBs) that are preferentially concentrated within genomic regions called hotspots; however, the factor(s) that specify the positions of meiotic DSB hotspots remain unclear. Results Here, we examined the frequency and distribution of R-loops, a type of functional chromatin structure comprising single-stranded DNA and a DNA:RNA hybrid, during budding yeast meiosis and found that the R-loops were changed dramatically throughout meiosis. We detected the formation of multiple de novo R-loops in the pachytene stage and found that these R-loops were associated with meiotic recombination during yeast meiosis. We show that transcription-replication head-on collisions could promote R-loop formation during meiotic DNA replication, and these R-loops are associated with Spo11. Furthermore, meiotic recombination hotspots can be eliminated by reversing the direction of transcription or replication, and reversing both of these directions can reconstitute the hotspots. Conclusions Our study reveals that R-loops may play dual roles in meiotic recombination. In addition to participation in meiotic DSB processing, some meiotic DSB hotspots may be originated from the transcription-replication head-on collisions during meiotic DNA replication.

In this article, we investigate the distributed Nash equilibrium (NE) seeking problem for the multi-cluster game under switching communication topologies. Specifically, the communication topology switches between a group of jointly connected digraphs. First, a new distributed NE seeking algorithm for the multi-cluster games is designed by the consensus protocol and gradient play rule under the switching communication topologies. Furthermore, in order to make the algorithm still applicable when the agent only knows part of the decision information, the leader-following consensus protocol is used to generate the estimates for all agents action in the cluster under the assumption that the switching topology between clusters is directed and strongly connected. A more general NE seeking algorithm for the multi-cluster games is designed. For these two algorithms, the results of local convergence and non-local convergence are given, respectively. Two examples verify the validity of the theoretical results.

Traditional teaching methods have faced unprecedented challenges as a result of educational reform, but it also presents limitless opportunities. The development of the flipped classroom teaching mode provides inspiration for the development of a PE teaching mode. This paper connects PE teaching with the “flipped classroom” teaching mode and designs an evaluation system for PE flipped classroom teaching based on the perspective of knowledge construction. The weight values of the contents of all levels of the evaluation dimensions of classroom teaching effectiveness are established in this paper, as well as the conceptual model and data table structure of the system database. In addition, using literature, questionnaires, and case studies, this paper investigates the effectiveness and application ideas of the “flipped classroom” teaching mode in PE classes. Experiments show that this method has an evaluation accuracy of 95.37 percent, which is about 13 percent higher than traditional methods. It is feasible and practicable in some ways. Additionally, flipping the classroom can increase student engagement, improve test scores, and increase teacher satisfaction. This study is expected to promote the use of the “flipped classroom” teaching mode in PE classes at colleges and universities, thereby speeding up the reform of PE education.

Diabetes is a metabolic disease which has been confirmed to be involved with abnormal or excessive body fat accumulation. There is still a lack of nationwide research in China to discuss the relationship between adiposity indicators included body mass index (BMI), waist circumference (WC), visceral adiposity index, waist-height ratio, waist-to-hip ratio (WHR) and diabetes. The question of which one is the best indicator of obesity to predict diabetes in China remains to be unclear.Data were collected from the China Health and Nutrition Survey (CHNS) in 2009, including 7,930 participants aged over 18 years old for cross-sectional analysis. Information about height, weight, WC, hip circumference, smoking status, alcohol consumption, physical activity, energy intake and blood samples were analyzed. Binary logistic regression models were used to explore the association of WC, BMI, WHR, waist-to-height ration (WHtR) and visceral adipose index (VAI) with the prevalence of diabetes in the 2009 CHNS respectively. Predictive potential of five adiposity indicators was validated by the area under the receiver operator characteristic curve (AUROC). The optimal cut-off points were determined by Youden's index, which was used to estimate the performance of adiposity indicators.The study shows patients in the highest quartile were more likely to have diabetes than those in the lowest quartile of WC (OR: 4.237, 95% CI: 3.265-5.499), BMI (OR: 3.312, 95% CI: 2.601-4.218), WHR (OR: 3.199, 95% CI: 2.493-4.104), WHtR (OR: 3.760, 95% CI: 2.891-4.890), VAI (OR: 4.347, 95% CI: 3.411-5.541). The area under the receiver operator characteristic curve of WC, BMI, WHR, WHtR and VAI for diabetes was 0.700, 0.663, 0.668, and 0.697 and 0.694, respectively. The optimal cut-offs regarding diabetes in Chinese are WHtR ≥0.520 for men and VAI ≥1.878 for women.Our findings indicate that WC, WHtR, BMI, WHR and VAI are all independent risk factors for diabetes among Chinese adults. WHtR is the most accurate indicator for diabetes in men, while VAI for women.

Mumps is a seasonal infectious disease, always occurring in winter and spring. In this study, we aim to analyze its epidemiological characteristics, transmissibility, and its correlation with meteorological variables.A seasonalThe seasonal double peak of annual incidence was mainly in May to July and November to December. There was high transmission at the median ofA relatively high level of transmissibility has been found in Xiamen City, leading to a continuous epidemic of mumps. Meteorological factors, especially air temperature and relative humidity, may be more closely associated with mumps than other factors.

Particulate matters with a diameter of 2.5 µm or less (PM2.5) were frequently reported to be associated with increased cancer incidences, but few studies have explored the associations between PM2.5 exposure and cancer survival. We retrospectively analyzed the association between PM2.5 exposure and the overall survival (OS) of cervical cancer patients who resided in 14 urban areas of the Liaoning Province, Northeastern China during January 2014-October 2021. Patients from urban areas who finished the recommended treatments with complete follow-up information were included. The PM2.5 monitoring data of each urban area of Liaoning Province was retrieved, and individual exposure to PM2.5 after diagnosis was calculated as the average daily concentration in the residence from the discharged day to death day or the last follow-up day. Log-rank tests and cox-regression were performed to examine the relationships between PM2.5 exposure and cervical cancer survival. A total of 1753 cervical cancer patients were finally included, among whom 804 (45.9%) were from Shenyang City, the capital of Liaoning Province. The median average daily concentration of PM2.5 that the patients were exposed to was 45.0 (interquartile range 38.2-50.0) µg/m3. Both log-rank tests (grouped by quartiles, p2.5 was significantly associated with shorter OS. Sensitivity analysis also confirmed the robustness of our findings. For the subgroup analysis, only the OS of stage II and stage III patients were associated with PM exposure. Our findings gave an insight that PM2.5 exposure was associated with shorter OS of cervical cancer patients.

Purpose. To summarize the relevant evidence for nondrug nursing programs in neonatal operational pain management. Methods. Computer search for the literature on neonatal procedural pain from 2015 to 2020 in Up To Date, JBI, NICE, SIGN, RNAO, NGC, PubMed, Cochrane Library, CNKI, and Wanfang database was conducted. All literature works that may meet the inclusion criteria were independently evaluated by two researchers to determine the quality grade of the articles. Results. Finally, 9 literature works were extracted, including 4 guidelines, 3 systematic reviews, and 2 evidence summaries. The relevant contents of the literature were extracted and summarized, and 20 pieces of the best evidence were obtained. Conclusion. Breast feeding, sweetener, Kangaroo mother care, sensory stimulation, nonnutritive sucking, and other nondrug nursing programs can reduce the neonatal operational pain, which has guiding significance in neonatal operational pain management.

The degradations of electrical parameters for depletion mode GaN devices in the cascode configuration under repetitive hard-switching stress are investigated in detail. With the help of TCAD simulations and comprehensive experimental analysis, two different mechanisms behind the degradations are demonstrated. Under a relatively low Vds hard-switching condition, hot electron injection is proved to be the only influence factor, which results in the increase of Rdson under low gate bias voltage. Furthermore, under the low Vds switching condition, influence of different stages on the degradation trend of the device is verified. It is found that the turn-on procedure has a greater degradation risk due to higher energy consumption. However, when Vds is high during hard-switching, the surface trapping effect is triggered due to high electric field at the end of gate field plate, and finally results in the device degradation trend. It results in the increase of the Rdson under high gate bias condition. Therefore, considering the stability and safety of power systems which adopt cascode devices as switches, shorter turn-on time or a soft-switching operation condition should be considered in the design.

The gut microbiota is significant for infants to grow and develop in the early stages of life. The breast milk microbiota directly or indirectly influences colonizing and the development of early infant intestinal microbiota. Therefore, we wanted to study the microbial diversity and correlation between breast milk and the infant gut. By sequencing the 16S rRNA V3–V4 regions of microbiome in infant feces 1, 14, 20, 30, and 90 days after delivery as well as those in breast milk using Illumina NovaSeq, we studied the component of microbiome in both human milk and infant stools, analyzed the diversity of microbiota, and explored the relationship between them. We found that the richest bacteria in breast milk were Acinetobacter, Stenotrophomonas, Sphingopyxis, Pseudomonas, and Streptococcus, with a small amount of Lactobacillus, Bifidobacterium, and Klebsiella. The infant feces were abundant in Bifidobacterium, Escherichia-Shigella, Klebsiella, Streptococcus, Serratia, Bacteroides, and Lactobacillus, with a small number of Acinetobacter and Pseudomonas. Acinetobacter, Bifidobacterium, Klebsiella, and Lactobacillus appeared in the breast milk and infant feces, suggesting that they were transferred from the breast milk to the infant’s gut.

Grassland caterpillars (Lepidoptera: Erebidae: Gynaephora) are important pests in alpine meadows of the Qinghai-Tibetan Plateau (QTP). These pests have morphological, behavioral, and genetic adaptations for survival in high-altitude environments. However, mechanisms underlying high-altitude adaptation in QTP Gynaephora species remain largely unknown. Here, we performed a comparative analysis of the head and thorax transcriptomes of G. aureata to explore the genetic basis of high-altitude adaptation. We detected 8,736 significantly differentially expressed genes (sDEGs) between the head and thorax, including genes related to carbohydrate metabolism, lipid metabolism, epidermal proteins, and detoxification. These sDEGs were significantly enriched in 312 Gene Ontology terms and 16 KEGG pathways. We identified 73 pigment-associated genes, including 8 rhodopsin-associated genes, 19 ommochrome-associated genes, 1 pteridine-associated gene, 37 melanin-associated genes, and 12 heme-associated genes. These pigment-associated genes were related to the formation of the red head and black thorax of G. aureata. A key gene, yellow-h, in the melanin pathway was significantly upregulated in the thorax, suggesting that it is related to the formation of the black body and contributed to the adaptation of G. aureata to low temperatures and high ultraviolet radiation in the QTP. Another key gene, cardinal, in the ommochrome pathway was significantly upregulated in the head and may be related to red warning color formation. We also identified 107 olfactory-related genes in G. aureata, including genes encoding 29 odorant-binding proteins, 16 chemosensory proteins, 22 odorant receptor proteins, 14 ionotropic receptors, 12 gustatory receptors, 12 odorant degrading enzymes, and 2 sensory neuron membrane proteins. Diversification of olfactory-related genes may be associated with the feeding habits of G. aureata, including larvae dispersal and searching for plant resources available in the QTP. These results provide new insights into high-altitude adaptation of Gynaephora in the QTP and may contribute to the development of new control strategies for these pests.

Supplementary Data

F-box and WD repeat domain containing 7 (FBXW7) is a substrate receptor of the ubiquitin ligase SKP1-Cullin1-F-box complex and a potent tumor suppressor that prevents unregulated cell growth and tumorigenesis. However, little is known about FBXW7-mediated control of cell metabolism and related functions in cancer therapy. Here, we report that FBXW7 expression inversely correlates with the expression levels of the key metabolic enzyme isocitrate dehydrogenase 1 (IDH1) in patients with glioma and public glioma datasets. Deletion of FBXW7 significantly increased both wild-type (WT) and mutant IDH1 expression, which was mediated by blocking degradation of sterol regulatory element binding protein 1 (SREBP1). The upregulation of neomorphic mutant IDH1 by FBXW7 deletion stimulated production of the oncometabolite 2-hydroxyglutarate at the expense of increasing pentose phosphate pathway activity and NADPH consumption, limiting the buffering ability against radiation-induced oxidative stress. In addition, FBXW7 knockout and IDH1 mutations induced nonhomologous end joining and homologous recombination defects, respectively. In vitro and in vivo, loss of FBXW7 dramatically enhanced the efficacy of radiation treatment in IDH1-mutant cancer cells. Taken together, this work identifies FBXW7 deficiency as a potential biomarker representing both DNA repair and metabolic vulnerabilities that sensitizes IDH1-mutant cancers to radiotherapy.Significance:Deficiency of FBXW7 causes defects in DNA repair and disrupts NADPH homeostasis in IDH1-mutant glioma cells, conferring high sensitivity to radiotherapy.

Background and aimsCompared with self-prepared LRD, a prepackaged low-residue diet (LRD) can improve patient compliance, but whether it can further improve the quality of bowel preparation is uncertain. The study aimed to compare the application of the prepackaged formula LRD with self-prepared LRD in bowel preparation for colonoscopy.MethodsA multicenter randomized controlled trial was conducted in 15 centers. The eligible subjects were randomly assigned to one of two groups: the formula LRD group and the self-prepared LRD group. On the day before the colonoscopy, subjects in the self-prepared LRD group were instructed to consume a restricted LRD prepared by themselves, while subjects in the formula LRD group were given six bags of prepackaged formula LRD and instructed to consume them according to their individual need. The primary outcome was an adequate bowel preparation rate. Secondary outcomes mainly included Boston Bowel Preparation Scale (BBPS) scores, dietary restriction compliance rate, tolerance, satisfaction, adenoma detection rate (ADR), and adverse reactions. The trial was registered at ClinicalTrials.gov under the identifier NCT03943758.ResultsA total of 550 subjects were recruited. Compared with the self-prepared LRD group, the formula LRD group showed a higher adequate bowel preparation rate (94.5 vs. 80.4%; P < 0.01), BBPS scores (7.87 ± 1.13 vs. 6.75 ± 1.47; P < 0.01), dietary compliance rate (92.4 vs. 78.9%; P < 0.01), tolerance (P < 0.01 in degree of hunger, intensity of physical strength, and negative influence on daily activities), satisfaction (8.56 ± 1.61 vs. 7.20 ± 2.02; P < 0.01), and ADR (25.6 vs. 16.0%; P < 0.01). There was no significant difference in adverse reactions.ConclusionCompared with self-prepared LRD, the formula LRD showed similar safety and higher bowel preparation quality, compliance, and tolerance in bowel preparation. More formula LRDs could be designed according to different dietary habits and ethnic populations, and further researches are warranted to confirm their effect.Clinical trial registrationhttps://register.clinicaltrials.gov, identifier: NCT03943758.

Identifying the PPR-E+-NUWA-DYW2 editosome improves our understanding of the C-to-U RNA editing in plant organelles. However, the mechanism of RNA editing remains to be elucidated. Here, we report that GLUTAMINE-RICH PROTEIN23 (GRP23), a previously identified nuclear transcription regulator, plays an essential role in mitochondrial RNA editing through interacting with MORF (multiple organellar RNA-editing factor) proteins and atypical DYW-type pentatricopeptide repeat (PPR) proteins. GRP23 is targeted to mitochondria, plastids, and nuclei. Analysis of the

Aim: This study evaluates the cost–effectiveness of imipenem/cilastatin/relebactam (IMI/REL) for treating hospital-acquired bacterial pneumonia and ventilator-associated bacterial pneumonia (HABP/VABP) in an ‘early adjustment prescribing scenario’. Methods: An economic model was constructed to compare two strategies: continuation of empiric piperacillin/tazobactam (PIP/TAZ) versus early adjustment to IMI/REL. A decision tree was used to depict the hospitalization period, and a Markov model used to capture long-term outcomes. Results: IMI/REL generated more quality-adjusted life years than PIP/TAZ, at an increased cost per patient. The incremental cost–effectiveness ratio of $17,529 per QALY is below the typical US willingness-to-pay threshold. Conclusion: IMI/REL may represent a cost-effective treatment for payers and a valuable option for clinicians, when considered alongside patient risk factors, local epidemiology, and susceptibility data.

sAffected by the burden reduction policy, out-of-school hours care places have become a hot issue of social concern. Taking Xi’an out-of-school hours care places as a research case, this paper discusses its location choice, spatial relationships and influencing factors using methods such as text analysis, spatial analysis, and mathematical statistics. The results show that: (1) the distribution of out-of-school hours care places in Xi’an is closely related to the community and schools. The names mostly use words such as “sunshine,” “teacher,” and “love,” which are mainly distributed on the lower floors (one to three floors), of which the first floor accounts for the largest proportion. (2) The high-value areas of out-of-school hours care places are mainly concentrated in the Lianhu District, Yanta District, Xincheng District, and the north Chang’an District. Their distribution has obvious directionality, showing a “northeast-southwest” trend, and the global spatial autocorrelation is positively correlated. (3) The spatial pattern of out-of-school hours care places is basically consistent with that of primary and secondary schools, and most of them are located within 1000 m of it. (4) The influencing factors mainly include the distribution of primary and secondary schools, residential areas, population density, house rent, and policies.

Background The coronavirus disease 2019 (COVID-19) outbreak has had a widespread and profound impact on people’s mental health. The factors associated with mental symptoms among men diagnosed with infertility, a disease closely related to psychological conditions, remain unclear. The aim of this study is to investigate the risk factors associated with mental symptoms among infertile Chinese men during the pandemic. Results A total of 4,098 eligible participants were recruited in this cross-sectional, nationwide study, including 2,034 (49.6%) with primary infertility and 2,064 (50.4%) with secondary infertility. The prevalence of mental health conditions was 36.3%, 39.6%, and 6.7% for anxiety, depression, and post-pandemic stress, respectively. Sexual dysfunction is associated with a higher risk with adjusted odds ratios (ORs) of 1.40 for anxiety, 1.38 for depression, and 2.32 for stress. Men receiving infertility drug therapy displayed a higher risk for anxiety (adjusted OR, 1.31) and depression (adjusted OR, 1.28) symptoms, while those receiving intrauterine insemination had a lower risk of anxiety (adjusted OR, 0.56) and depression (adjusted OR, 0.55) symptoms. Conclusion The COVID-19 pandemic has had a significant psychological impact on infertile men. Several psychologically vulnerable populations were identified, including individuals with sexual dysfunction, respondents receiving infertility drug therapy, and those experiencing control measures for COVID-19. The findings provide a comprehensive profile of the mental health status of infertile Chinese men during the COVID-19 outbreak and provide potential psychological intervention strategies.