Sleep-promoting neurons remodel their response properties to calibrate sleep drive with environmental demands.

Falling asleep at the wrong time can place an individual at risk of immediate physical harm. However, not sleeping degrades cognition and adaptive behavior. To understand how animals match sleep need with environmental demands, we used live-brain imaging to examine the physiological response properties of the dorsal fan-shaped body (dFB) following interventions that modify sleep (sleep deprivation, starvation, time-restricted feeding, memory consolidation) in Drosophila. We report that dFB neurons change their physiological response-properties to dopamine (DA) and allatostatin-A (AstA) in response to different types of waking. That is, dFB neurons are not simply passive components of a hard-wired circuit. Rather, the dFB neurons intrinsically regulate their response to the activity from upstream circuits. Finally, we show that the dFB appears to contain a memory trace of prior exposure to metabolic challenges induced by starvation or time-restricted feeding. Together, these data highlight that the sleep homeostat is plastic and suggests an underlying mechanism.

Longitudinal Associations Between Reactive and Proactive Aggression and Depression in Early Adolescence: Between- and Within-Person Effects.

Depressive symptoms and aggression often co-occur, and previous studies have found different bidirectional links between depressive symptoms and aggression, suggesting inconsistent developmental cascades. Moreover, it is unclear whether different functions of aggression are differentially associated with depressive symptoms over time. The present study examined the longitudinal associations of reactive and proactive aggression with depressive symptoms in early adolescence. Adolescents (n = 942, 50.7% girls; mean age = 12.54 years, SD = 0.42) were surveyed annually over three years (2019-2021). Random-intercept cross-lagged panel models were used to disentangle between- and within-person effects. The results showed moderate between-person associations of depressive symptoms with the two aggressive functions. And depressive symptoms were more highly associated with reactive aggression than with proactive aggression. However, the state-level bidirectional cross-lagged associations between reactive and proactive aggression and depressive symptoms were not significant. This study highlights the stable trait-like association between depressive symptoms and reactive aggression, and the absence of state-level bidirectional cross-lagged associations challenges previous developmental cascades in adolescents.

YIPF5 (p.W218R) mutation induced primary microcephaly in rabbits.

Primary microcephaly (PMCPH) is a rare autosomal recessive neurodevelopmental disorder with a global prevalence of PMCPH ranging from 0.0013% to 0.15%. Recently, a homozygous missense mutation in YIPF5 (p.W218R) was identified as a causative mutation of severe microcephaly. In this study, we constructed a rabbit PMCPH model harboring YIPF5 (p.W218R) mutation using SpRY-ABEmax mediated base substitution, which precisely recapitulated the typical symptoms of human PMCPH. Compared with wild-type controls, the mutant rabbits exhibited stunted growth, reduced head circumference, altered motor ability, and decreased survival rates. Further investigation based on model rabbit elucidated that altered YIPF5 function in cortical neurons could lead to endoplasmic reticulum stress and neurodevelopmental disorders, interference of the generation of apical progenitors (APs), the first generation of progenitors in the developing cortex. Furthermore, these YIPF5-mutant rabbits support a correlation between unfolded protein responses (UPR) induced by endoplasmic reticulum stress (ERS), and the development of PMCPH, thus providing a new perspective on the role of YIPF5 in human brain development and a theoretical basis for the differential diagnosis and clinical treatment of PMCPH. To our knowledge, this is the first gene-edited rabbit model of PMCPH. The model better mimics the clinical features of human microcephaly than the traditional mouse models. Hence, it provides great potential for understanding the pathogenesis and developing novel diagnostic and therapeutic approaches for PMCPH.

A novel probe set for the phylogenomics and evolution of RTA spiders.

Spiders are important models for evolutionary studies of web building, sexual selection and adaptive radiation. The recent development of probes for UCE (ultra-conserved element)-based phylogenomic studies has shed light on the phylogeny and evolution of spiders. However, the two available UCE probe sets for spider phylogenomics (Spider and Arachnida probe sets) have relatively low capture efficiency within spiders, and are not optimized for the retrolateral tibial apophysis (RTA) clade, a hyperdiverse lineage that is key to understanding the evolution and diversification of spiders. In this study, we sequenced 15 genomes of species in the RTA clade, and using eight reference genomes, we developed a new UCE probe set (41 845 probes targeting 3802 loci, labelled as the RTA probe set). The performance of the RTA probes in resolving the phylogeny of the RTA clade was compared with the Spider and Arachnida probes through an in-silico test on 19 genomes. We also tested the new probe set empirically on 28 spider species of major spider lineages. The results showed that the RTA probes recovered twice and four times as many loci as the other two probe sets, and the phylogeny from the RTA UCEs provided higher support for certain relationships. This newly developed UCE probe set shows higher capture efficiency empirically and is particularly advantageous for phylogenomic and evolutionary studies of RTA clade and jumping spiders.

Trends in respiratory diseases before and after the COVID-19 pandemic in China from 2010 to 2021.

BACKGROUND: The ongoing benefits of coronavirus disease 2019 (COVID-19) nonpharmaceutical interventions (NPIs) for respiratory infectious diseases in China are still unclear. We aimed to explore the changes in seven respiratory infectious diseases before, during, and after COVID-19 in China from 2010 to 2021. METHODS: The monthly case numbers of seven respiratory infectious diseases were extracted to construct autoregressive integrated moving average (ARIMA) models. Eight indicators of NPIs were chosen from the COVID-19 Government Response Tracker system. The monthly case numbers of the respiratory diseases and the eight indicators were used to establish the Multivariable generalized linear model (GLM) to calculate the incidence rate ratios (IRRs). RESULTS: Compared with the year 2019, the percentage changes in 2020 and 2021 were all below 100% ranging from 3.81 to 84.71%. Pertussis and Scarlet fever started to increase in 2021 compared with 2020, with a percentage change of 183.46 and 171.49%. The ARIMA model showed a good fit, and the predicted data fitted well with the actual data from 2010 to 2019, but the predicted data was bigger than the actual number in 2020 and 2021. All eight indicators could negatively affect the incidence of respiratory diseases. The seven respiratory diseases were significantly reduced during the COVID-19 pandemic in 2020 and 2021 compared with 2019, with significant estimated IRRs ranging from 0.06 to 0.85. In the GLM using data for the year 2020 and 2021, the IRRs were not significant after adjusting for the eight indicators in multivariate analysis. CONCLUSION: Our study demonstrated the incidence of the seven respiratory diseases decreased rapidly during the COVID-19 pandemic in 2020 and 2021. At the end of 2021, we did see a rising trend for the seven respiratory diseases compared to the year 2020 when the NPIs relaxed in China, but the rising trend was not significant after adjusting for the NPIs indicators. Our study showed that NPIs have an effect on respiratory diseases, but Relaxation of NPIs might lead to the resurgence of respiratory diseases.

A long trend of sexually transmitted diseases before and after the COVID-19 pandemic in China (2010-21).

BACKGROUND: The longer ongoing benefits of coronavirus disease 2019 (COVID-19) non-pharmaceutical interventions (NPIs) for sexually transmitted diseases (STDs) in China are still unclear. We aimed to explore the changes in five STDs (AIDS, hepatitis B, hepatitis C, gonorrhoea, and syphilis) before, during, and after the COVID-19 pandemic in mainland China, from 2010 to 2021. METHODS: The number of the monthly reported cases of the five STDs were extracted from the website to construct the Joinpoint regression and autoregressive integrated moving average (ARIMA) models. Eight indicators reflecting NPIs were chosen from the COVID-19 Government Response Tracker system. The STDs and eight indicators were used to establish the Multivariable generalised linear model (GLM) to calculate the incidence rate ratios (IRRs). RESULTS: With the exception of hepatitis B, the other four STDs (AIDS, hepatitis C, gonorrhoea, and syphilis) had a positive average annual percent change over the past 12years. All the ARIMA models had passed the Ljung-Box test, and the predicted data fit well with the data from 2010 to 2019. All five STDs were significantly reduced in 2020 compared with 2019, with significant estimated IRRs ranging from 0.88 to 0.92. In the GLM, using data for the years 2020 (February-December) and 2021, the IRRs were not significant after adjusting for the eight indicators in multivariate analysis. CONCLUSION: Our study demonstrated that the incidence of the five STDs decreased rapidly during the COVID-19 pandemic in 2020. A recovery of STDs in 2021 was found to occur compared with that in 2020, but the rising trend disappeared after adjusting for the NPIs. Our study demonstrated that NPIs have an effect on STDs, but the relaxation of NPI usage might lead to a resurgence.

Adaptive Optical Closed-Loop Control Based on the Single-Dimensional Perturbation Descent Algorithm.

Modal-free optimization algorithms do not require specific mathematical models, and they, along with their other benefits, have great application potential in adaptive optics. In this study, two different algorithms, the single-dimensional perturbation descent algorithm (SDPD) and the second-order stochastic parallel gradient descent algorithm (2SPGD), are proposed for wavefront sensorless adaptive optics, and a theoretical analysis of the algorithms' convergence rates is presented. The results demonstrate that the single-dimensional perturbation descent algorithm outperforms the stochastic parallel gradient descent (SPGD) and 2SPGD algorithms in terms of convergence speed. Then, a 32-unit deformable mirror is constructed as the wavefront corrector, and the SPGD, single-dimensional perturbation descent, and 2SPSA algorithms are used in an adaptive optics numerical simulation model of the wavefront controller. Similarly, a 39-unit deformable mirror is constructed as the wavefront controller, and the SPGD and single-dimensional perturbation descent algorithms are used in an adaptive optics experimental verification device of the wavefront controller. The outcomes demonstrate that the convergence speed of the algorithm developed in this paper is more than twice as fast as that of the SPGD and 2SPGD algorithms, and the convergence accuracy of the algorithm is 4% better than that of the SPGD algorithm.

End-to-end metasurface inverse design for single-shot multi-channel imaging.

We introduce end-to-end inverse design for multi-channel imaging, in which a nanophotonic frontend is optimized in conjunction with an image-processing backend to extract depth, spectral and polarization channels from a single monochrome image. Unlike diffractive optics, we show that subwavelength-scale "metasurface" designs can easily distinguish similar wavelength and polarization inputs. The proposed technique integrates a single-layer metasurface frontend with an efficient Tikhonov reconstruction backend, without any additional optics except a grayscale sensor. Our method yields multi-channel imaging by spontaneous demultiplexing: the metaoptics front-end separates different channels into distinct spatial domains whose locations on the sensor are optimally discovered by the inverse-design algorithm. We present large-area metasurface designs, compatible with standard lithography, for multi-spectral imaging, depth-spectral imaging, and "all-in-one" spectro-polarimetric-depth imaging with robust reconstruction performance (≲ 10% error with 1% detector noise). In contrast to neural networks, our framework is physically interpretable and does not require large training sets. It can be used to reconstruct arbitrary three-dimensional scenes with full multi-wavelength spectra and polarization textures.

CircSOS2 promotes cervical squamous cell carcinoma by regulation of proliferation, cell cycle, apoptosis, migration, invasion, and glycolysis by targeting miR-543/FNDC3B axis.

BACKGROUND: Cervical squamous cell carcinoma (SCC) is a common subtype of cervical cancer. Circular RNAs (circRNAs) have been demonstrated as vital regulators in gene regulation and malignant tumor progression. Therefore, the precise role of circular RNA salt overly-sensitive 2 (circSOS2) was investigated in SCC. METHODS: The relative expression levels of circSOS2, microRNA-543 (miR-543), and Fibronectin type III domain containing 3B (FNDC3B) were determined by real-time quantitative polymerase chain reaction (RT-qPCR) and Western blot assays. The correlation between percent survival times of SCC patients and circSOS2 level was presented by Kaplan-Meier Plotter analysis. The cell proliferation was measured by MTT and colony-forming assays. Flow cytometry assay was used to assess apoptosis and cell cycle distribution. The migration and invasion were measured by transwell assay. The glycolysis was analyzed by extracellular acidification rate (ECAR) assay, Glucose Assay Kit, and Lactate Assay Kit. The interaction relationship between miR-543 and circSOS2 or FNDC3B was analyzed by dual-luciferase reporter, RNA immunoprecipitation (RIP), and RNA pull-down assays. A xenograft experiment was established to clarify the functional role of circSOS2 inhibition in viv. RESULTS: CircSOS2 was highly expressed in SCC tissues and cells; besides, its expression level was closely associated with poor prognosis. Loss-of-functional experiments revealed that suppression of circSOS2 repressed proliferation, cell cycle process, migration, invasion, and glycolysis while induced apoptosis in SCC cells, which was overturned by inhibition of miR-543. In addition, miR-543 was downregulated and negatively correlated with circSOS2 expression in SCC tissues. We also found that overexpression of miR-543 impeded proliferation, cell cycle process, migration, invasion, and glycolysis while induced apoptosis in SCC cells by targeting FNDC3B. The silencing of circSOS2 impeded tumorigenesis in vivo. CONCLUSION: CircSOS2 conferred an oncogenic function in SCC by regulation of proliferation, cell cycle, apoptosis, migration, invasion, and glycolysis of SCC cells, which was contributed to its interactions with miR-543 and FNDC3B.

Novel Bispecific Aptamer Enhances Immune Cytotoxicity Against MUC1-Positive Tumor Cells by MUC1-CD16 Dual Targeting.

A promising strategy in cancer immunotherapy is the employment of a bispecific agent that can bind with both tumor markers and immunocytes for recruitment of lymphocytes to tumor sites and enhancement of anticancer immune reactions. Mucin1 (MUC1) is a tumor marker overexpressed in almost all adenocarcinomas, making it a potentially important therapeutic target. CD16 is expressed in several types of immunocytes, including NK cells, γδ-T cells, monocytes, and macrophages. In this study, we constructed the first bispecific aptamer (BBiApt) targeting both MUC1 and CD16. This aptamer consisted of two MUC1 aptamers and two CD16 aptamers linked together by three 60 nt DNA spacers. Compared with monovalent MUC1 or CD16 aptamers, BBiApt showed more potent avidity to both MUC1-positive tumor cells and CD16-positive immunocytes. Competition experiments indicated that BBiApt and monovalent aptamers bound to the same sites on the target cells. Moreover, BBiApt recruited more CD16-positive immunocytes around MUC1-positive tumor cells and enhanced the immune cytotoxicity against the tumor cells in vitro. The results suggest that, apart from bispecific antibodies, bispecific aptamers may also potentially serve as a novel strategy for targeted enhancement of antitumor immune reactions against MUC1-expressing malignancies.

[Effect of Compound Zhajin Granule on Toll-like Receptor 4 Signaling Pathway in Nonalcoholic Steatohepatitis Mice].

OBJECTIVE: To observe the effect of Compound Zhajin Granule (CZG) on Toll-like re-ceptor 4 (TLR4) signaling pathway in high-fructose corn syrup induced NASH mice. METHODS: Thirty 6-week-old male C3H mice were divided into the high fat and high fructose (HFHFr) group (n = 20) and the control group (n = 10) according to body weight. Mice in the HFHFr group ate high fat diet and drank 20% fructose water, while those in the control group ate common diet and drank common water. After 8 weeks mice in the HFHFr group were divided into two group according to body weight, the HFHFr group and the CZG group, 10 in each group. Mice in the CZG group were fed with high fat forage and 20% fructose water, and administered with 50 mL/kg 12. 8% CZG (prepared by hawthorn, Radix Curcumae, Alisma Orientale, Fritillaria Thunbergii, Silybum Marianum, peach seed in the ratio of 3:1.5:1.5:2:1.5:2:1) by gastrogavage. Mice in the HFHFr group were fed in the same way and daily administered with equal volume of distilled water by gastrogavage. Sixteen weeks later all mice were sacrificed. Body weight, liver wet weight, liver function, and lipid metabolism were detected. Pathological changes of liver tissues were assessed by HE staining, oil red O staining, and Masson staining. Expressions of TLR4, myeloid differentiation factor 88 (MyD88), tumor necrosis factor-alpha (TNF-α) were detected using immunohistochemical staining and real-time fluorescent quantitative PCR. RESULTS: Body weight, alanine aminotransferase (ALT), aspartate aminotransferase (AST) were obviously lower in the CZG group than in the HFHFr group (P < 0.05); oil red O stained area and density were decreased more in the CZG group than in the control group. HE staining showed ballooning inflammation was reduced more in the CZG group than in the HFHFr group. Masson staining was negative. Positive rates of TLR4 and MyD88 and mRNA expressions were significantly lower in the CZG group than in the HFHFr group (all P < 0.05). CONCLUSION: CZG could significantly inhibit TLR4 signaling pathway of liver in NASH mice.

Photoselective Vaporization of the Prostate and Simultaneous Suprapubic Cystostomy for the Treatment of Benign Prostatic Hyperplasia in Patients with Mild to Severe Detrusor Underactivity.

INTRODUCTION: This study investigated the clinical efficacy and safety of photoselective vaporization of the prostate (PVP) and simultaneous suprapubic cystostomy for benign prostatic hyperplasia (BPH) in patients with mild to severe detrusor underactivity (DU). SUBJECTS AND METHODS: Seventy-eight patients with BPH were divided into 3 groups according to the severity of DU: mild DU group, moderate DU group and severe DU group. The preoperative and postoperative data, including the detrusor pressure at maximum flow (Pdetmax), bladder compliance, maximum urinary flow (Qmax), postvoid residual urine (PVR) values, International Prostate Symptom Score (IPSS) and quality of life (QoL) were evaluated. RESULTS: The therapeutic effectiveness including cure and improvement in mild and moderate DU group was significantly higher than that of the severe group. Compared to the preoperative values, Pdetmax, bladder compliance, Qmax, PVR, IPSS and QoL scores at 12 months postoperatively had significantly improved. In addition, the above parameters at 12 months postoperatively in the mild or moderate DU group had significant difference compared to the severe DU group. CONCLUSION: PVP and simultaneous suprapubic cystostomy seem to be an appropriate treatment modality in BPH patients with mild and/or moderate DU as well as in patients with severe DU and slightly reduced bladder compliance.

Two new species of the genus Cheiracanthium C. L. Koch, 1839 (Araneae, Cheiracanthiidae) from China.

Two species of the long-legged sac spider genus Cheiracanthium C. L. Koch, 1839 collected from China are diagnosed and described as new to science: Cheiracanthiumbannaensissp. nov. (♂♀) from Yunnan Province and C.bifurcatumsp. nov. (♂♀) from Xinjiang Uyger Autonomous Region. Photos of the habitus and copulatory organs are given. In addition, DNA barcode information of the two new species is provided.

All-Glass 100 mm Diameter Visible Metalens for Imaging the Cosmos.

Metasurfaces, optics made from subwavelength-scale nanostructures, have been limited to millimeter-sizes by the scaling challenge of producing vast numbers of precisely engineered elements over a large area. In this study, we demonstrate an all-glass 100 mm diameter metasurface lens (metalens) comprising 18.7 billion nanostructures that operates in the visible spectrum with a fast f-number (f/1.5, NA = 0.32) using deep-ultraviolet (DUV) projection lithography. Our work overcomes the exposure area constraints of lithography tools and demonstrates that large metasurfaces are commercially feasible. Additionally, we investigate the impact of various fabrication errors on the imaging quality of the metalens, several of which are specific to such large area metasurfaces. We demonstrate direct astronomical imaging of the Sun, the Moon, and emission nebulae at visible wavelengths and validate the robustness of such metasurfaces under extreme environmental thermal swings for space applications.

Elevated extracellular matrix protein 1 in circulating extracellular vesicles supports breast cancer progression under obesity conditions.

The cargo content in small extracellular vesicles (sEVs) changes under pathological conditions. Our data shows that in obesity, extracellular matrix protein 1 (ECM1) protein levels are significantly increased in circulating sEVs, which is dependent on integrin-ß2. Knockdown of integrin-ß2 does not affect cellular ECM1 protein levels but significantly reduces ECM1 protein levels in the sEVs released by these cells. In breast cancer (BC), overexpressing ECM1 increases matrix metalloproteinase 3 (MMP3) and S100A/B protein levels. Interestingly, sEVs purified from high-fat diet-induced obesity mice (D-sEVs) deliver more ECM1 protein to BC cells compared to sEVs from control diet-fed mice. Consequently, BC cells secrete more ECM1 protein, which promotes cancer cell invasion and migration. D-sEVs treatment also significantly enhances ECM1-mediated BC metastasis and growth in mouse models, as evidenced by the elevated tumor levels of MMP3 and S100A/B. Our study reveals a mechanism and suggests sEV-based strategies for treating obesity-associated BC.

MicroRNAs Regulate Function in Atherosclerosis and Clinical Implications.

Background: Atherosclerosis is considered the most common cause of morbidity and mortality worldwide. Athermanous plaque formation is pathognomonic of atherosclerosis. The main feature of atherosclerosis is the formation of plaque, which is inseparable from endothelial cells, vascular smooth muscle cells, and macrophages. MicroRNAs, a small highly conserved noncoding ribonucleic acid (RNA) molecule, have multiple biological functions, such as regulating gene transcription, silencing target gene expression, and affecting protein translation. MicroRNAs also have various pharmacological activities, such as regulating cell proliferation, apoptosis, and metabolic processes. It is noteworthy that many studies in recent years have also proved that microRNAs play a role in atherosclerosis. Methods: To summarize the functions of microRNAs in atherosclerosis, we reviewed all relevant articles published in the PubMed database before June 2022, with keywords "atherosclerosis," "microRNA," "endothelial cells," "vascular smooth muscle cells," "macrophages," and "cholesterol homeostasis," briefly summarized a series of research progress on the function of microRNAs in endothelial cells, vascular smooth muscle cells, and macrophages and atherosclerosis. Results and Conclusion. In general, the expression levels of some microRNAs changed significantly in different stages of atherosclerosis pathogenesis; therefore, MicroRNAs may become new diagnostic biomarkers for atherosclerosis. In addition, microRNAs are also involved in the regulation of core processes such as endothelial dysfunction, plaque formation and stabilization, and cholesterol metabolism, which also suggests the great potential of microRNAs as a therapeutic target.

New Targets and Strategies for Rheumatoid Arthritis: From Signal Transduction to Epigenetic Aspect.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that can lead to joint damage and even permanent disability, seriously affecting patients' quality of life. At present, the complete cure for RA is not achievable, only to relieve the symptoms to reduce the pain of patients. Factors such as environment, genes, and sex can induce RA. Presently, non-steroidal anti-inflammatory drugs, DRMADs, and glucocorticoids are commonly used in treating RA. In recent years, some biological agents have also been applied in clinical practice, but most have side effects. Therefore, finding new mechanisms and targets for treating RA is necessary. This review summarizes some potential targets discovered from the perspective of epigenetics and RA mechanisms.

An integrated model: marital effect on adolescent behavioral problems through siblings.

Introduction: Few studies have simultaneously focused on the effects of marital conflict and marital intimacy on adolescent development, and little is known about the role of sibling relationships. Thus, this study examined the association between marital relationships and adolescent behavioral problems, including depressive symptoms and aggressive behavior. At the same time, we explored the mediating role of sibling hostility and sibling affection and the moderating effect of birth order in multichild families in China. Methods: Participants included 842 adolescents (Mage = 12.60, 46.2% boys) from Henan Province. Marital relationship, sibling relationship, birth order, depressive symptoms and aggressive behavior were assessed by a self-administered questionnaire. SEM was then used to examine the role of sibling relationships and birth order in the association between marital relationship and adolescent behavioral problems. Results: Our results showed that marital intimacy was negatively correlated with depressive symptoms and aggressive behavior, while marital conflict was positively correlated with them. Marital intimacy was associated with depressive symptoms and aggressive behavior through both sibling hostility and sibling affection. Marital conflict was indirectly associated with depressive symptoms and aggressive behavior through sibling hostility. In addition, the first-born adolescents were more sensitive to marital intimacy. Discussion: Given that the occurrence of adolescent behavioral problems is more common in contemporary society, our findings suggest that establishing a more intimate and warmer family atmosphere and promoting positive interactions between siblings may help control adolescent mental health problems.

The relationship between single nucleotide polymorphisms and skin cancer susceptibility: A systematic review and network meta-analysis.

Background: Single nucleotide polymorphisms (SNPs) interfere with the function of certain genes and thus may influence the probability of skin cancer. The correlation between SNPs and skin cancer (SC) lacks statistical power, however. Therefore, the purpose of this study was to identify the gene polymorphisms involved in skin cancer susceptibility using network meta-analysis and to determine the relationship between SNPs and SC risk. Methods: PubMed, Embase, and Web of Science were searched for articles including "SNP" and different types of SC as keywords between January 2005 and May 2022. The Newcastle-Ottawa Scale was used to assess bias judgments. The odds ratio (ORs) and their 95% confidence intervals (CIs) were determined to estimate heterogeneity within and between studies. Meta-analysis and network meta-analysis were carried out to identify the SNPs associated with SC. The P-score of each SNP was compared to obtain the rank of probability. Subgroup analyses were performed by cancer type. Results: A total of 275 SNPs from 59 studies were included in the study. Two subgroup SNP networks using the allele model and dominant model were analyzed. The alternative alleles of rs2228570 (FokI) and rs13181 (ERCC2) were the first-ranking SNPs in both subgroups one and two of the allele model, respectively. The homozygous dominant genotype and heterozygous genotype of rs475007 in subgroup one and the homozygous recessive genotype of rs238406 in subgroup two were most likely to be associated with skin cancer based on the dominant model. Conclusions: According to the allele model, SNPs FokI rs2228570 and ERCC2 rs13181 and, according to the dominant model, SNPs MMP1 rs475007 and ERCC2 rs238406 are closely linked to SC risk.

Extending the dosing interval of COVID-19 vaccination leads to higher rates of seroconversion in people living with HIV.

Introduction: Vaccination against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection is an effective way of protecting individuals from severe coronavirus disease 2019 (COVID-19). However, immune responses to vaccination vary considerably. This study dynamically assessed the neutralizing antibody (NAb) responses to the third dose of the inactivated COVID-19 vaccine administered to people living with human immunodeficiency virus (HIV; PLWH) with different inoculation intervals. Methods: A total of 171 participants were recruited: 63 PLWH were placed in cohort 1 (with 3-month interval between the second and third doses), while 95 PLWH were placed in cohort 2 (with 5-month interval between the second and third doses); 13 individuals were enrolled as healthy controls (HCs). And risk factors associated with seroconversion failure after vaccination were identified via Cox regression analysis. Results: At 6 months after the third vaccination, PLWH in cohort 2 had higher NAb levels (GMC: 64.59 vs 21.99, P < 0.0001) and seroconversion rate (68.42% vs 19.05%, P < 0.0001). A weaker neutralizing activity against the SARSCoV-2 Delta variant was observed (GMT: 3.38 and 3.63, P < 0.01) relative to the wildtype strain (GMT: 13.68 and 14.83) in both cohorts. None of the participants (including HCs or PLWH) could mount a NAb response against Omicron BA.5.2. In the risk model, independent risk factors for NAb seroconversion failure were the vaccination interval (hazed ration [HR]: 0.316, P < 0.001) and lymphocyte counts (HR: 0.409, P < 0.001). Additionally, PLWH who exhibited NAb seroconversion after vaccination had fewer initial COVID-19 symptoms when infected with Omicron. Discussion: This study demonstrated that the third vaccination elicited better NAb responses in PLWH, when a longer interval was used between vaccinations. Since post-vaccination seroconversion reduced the number of symptoms induced by Omicron, efforts to protect PLWH with risk factors for NAb seroconversion failure may be needed during future Omicron surges. Clinical trial registration: https://beta.clinicaltrials.gov/study/NCT05075070, identifier NCT05075070.