Delayed postoperative neurological deficits from scoliosis correction: a case series and systematic review on clinical characteristics, treatment, prognosis, and recovery.

OBJECTIVE: This study was designed to investigate the clinical features, treatment modalities, and risk factors influencing neurological recovery in patients who underwent scoliosis correction with delayed postoperative neurological deficit (DPND). METHODS: Three patients with DPND were identified from 2 central databases for descriptive analysis. Furthermore, all DPND cases were retrieved from the PubMed and Embase databases. Neurological function recovery was categorized into complete and incomplete recovery groups based on the American Spinal Injury Association (ASIA) impairment scale. RESULTS: Two patients were classified as type 3, and one was classified as type 2 based on the MRI spinal cord classification. Intraoperative neurophysiological monitoring (IONM) was consistently negative throughout the corrective procedure, and intraoperative wake-up tests were normal. The average time to DPND development was 11.8 h (range, 4-18 h), and all three patients achieved complete recovery of neurological function after undergoing revision surgery. A total of 14 articles involving 31 patients were included in the literature review. The mean time to onset of DPND was found to be 25.2 h, and 85.3% (29/34) of patients experienced DPND within the first 48 h postoperatively, with the most common initial symptoms being decreased muscle strength and sensation (26 patients, 83.9%). Regarding neurological function recovery, 14 patients were able to reach ASIA grade E, while 14 patients were not able to reach ASIA grade E. Univariate analysis revealed that preoperative diagnosis (p = 0.004), operative duration (p = 0.017), intraoperative osteotomy method (p = 0.033), level of neurological deficit (p = 0.037) and deficit source (p = 0.0358) were significantly associated with neurological outcomes. Furthermore, multivariate regression analysis indicated a strong correlation between preoperative diagnosis (p = 0.003, OR, 68.633; 95% CI 4.299-1095.657) and neurological prognosis. CONCLUSION: Our findings indicate that spinal cord ischemic injury was a significant factor for patients experiencing DPND and distraction after corrective surgery may be a predisposing factor for spinal cord ischemia. Additionally, it is important to consider the possibility of DPND when limb numbness and decreased muscle strength occur within 48 h after corrective scoliosis surgery. Moreover, emergency surgical intervention is highly recommended for DPND caused by mechanical compression factors with a promising prognosis for neurological function, emphasizing the importance of taking into account preoperative orthopedic diagnoses when evaluating the potential for neurological recovery.

Isolation, characterization and therapeutic evaluation of a new Acinetobacter virus Abgy202141 lysing Acinetobacter baumannii.

Acinetobacter baumannii is an opportunistic pathogen that easily resists currently available antibiotics. Phages are considered alternative therapeutic agents to conventional antibiotics for the treatment of multidrug-resistant bacteria. We isolated an Acinetobacter virus Abgy202141 from underground sewage in a residential area of Guiyang City in China. Transmission electron microscopy (TEM) analysis showed that Acinetobacter virus Abgy202141 has an icosahedral head attached to a tail. This phage infects A. baumannii strain GY-4, and was found to have a short latent period of 5 min and with a burst size of 189 particles per infected host cell. Additionally, Acinetobacter virus Abgy202141 remained stable at different concentrations of chloroform and varying pH levels and temperatures. Based on SDS-PAGE analysis, it contained 14 proteins with molecular weights ranging from 12 to 125 kDa. The double-strand (ds) DNA genome of Acinetobacter virus Abgy202141 consisted of 41,242 bp with a GC content of 39.4%. It contained 50 open reading frames (ORFs), of which 29 ORFs had identified functions, but no virulence-related genes, antibiotic-resistance genes, or tRNAs were found. Phylogenetic analysis indicated that Acinetobacter virus Abgy202141 was a new phage in the Friunavirus genus. Acinetobacter virus Abgy202141 also showed the ability to prevent A. baumannii infections in the Galleria mellonella in vivo model.

A Blockchain-Assisted Security Protocol for Group Handover of MTC Devices in 5G Wireless Networks.

In the realm of the fifth-generation (5G) wireless cellular networks, renowned for their dense connectivity, there lies a substantial facilitation of a myriad of Internet of Things (IoT) applications, which can be supported by the massive machine-type communication (MTC) technique, a fundamental communication framework. In some scenarios, a large number of machine-type communication devices (MTCD) may simultaneously enter the communication coverage of a target base station. However, the current handover mechanism specified by the 3rd Generation Partnership Project (3GPP) Release 16 incurs high signaling overhead within the access and core networks, which may have negative impacts on network efficiency. Additionally, other existing solutions are vulnerable to malicious attacks such as Denial of Service (DoS), Distributed Denial of Service (DDoS) attacks, and the failure of Key Forward Secrecy (KFS). To address this challenge, this paper proposes an efficient and secure handover authentication protocol for a group of MTCDs supported by blockchain technology. This protocol leverages the decentralized nature of blockchain technology and combines it with certificateless aggregate signatures to mutually authenticate the identity of a base station and a group of MTCDs. This approach can reduce signaling overhead and avoid key escrow while significantly lowering the risk associated with single points of failure. Additionally, the protocol protects device anonymity by encrypting device identities with temporary anonymous identity markers with the Elliptic Curve Diffie-Hellman (ECDH) to abandon serial numbers to prevent linkage attacks. The resilience of the proposed protocol against predominant malicious attacks has been rigorously validated through the application of the BAN logic and Scyther tool, underscoring its robust security attributes. Furthermore, compared to the existing solutions, the proposed protocol significantly reduces the authentication cost for a group of MTCDs during handover, while ensuring security, demonstrating commendable efficiency.

Detoxification and Activating Blood Circulation Decoction Promotes Reendothelialization of Damaged Blood Vessels via VEGF Signaling Pathway Activation by miRNA-126.

The occurrence of in-stent restenosis (ISR) poses a significant challenge for percutaneous coronary intervention (PCI). Thus, the promotion of vascular reendothelialization is essential to inhibit endothelial proliferation. In this study, we clarified the mechanism by which Detoxification and Activating Blood Circulation Decoction (DABCD) promotes vascular reendothelialization to avoid ISR by miRNA-126-mediated modulation of the vascular endothelial growth factor (VEGF) signaling pathway. A rat model of post-PCI restenosis was established by balloon injury. The injured aortic segment was collected 14 and 28 d after model establishment. Our findings indicate that on the 14th and 28th days following balloon injury, DABCD reduced intimal hyperplasia and inflammation and promoted vascular reendothelialization. Additionally, DABCD markedly increased nitric oxide (NO) expression and significantly decreased ET-1 production in rat serum. DABCD also increased the mRNA level of endothelial nitric oxide synthase (eNOS) and the protein expression of VEGF, p-Akt, and p-extracellular signal-regulated kinase (ERK)1/2 in vascular tissue. Unexpectedly, the expression of miR-126a-5p mRNA was significantly lower in the aortic tissue of balloon-injured rats than in the aortic tissue of control rats, and higher miR-126a-5p levels were observed in the DABCD groups. The results of this study indicated that the vascular reendothelialization effect of DABCD on arterial intimal injury is associated with the inhibition of neointimal formation and the enhancement of vascular endothelial activity. More specifically, the effects of DABCD were mediated, at least in part, through miR-126-mediated VEGF signaling pathway activation.

Promising cellulose-based functional gels for advanced biomedical applications: A review.

Novel biomedical materials provide a new horizon for the diagnosis/treatment of diseases and tissue repair in medical engineering. As the most abundant biomass polymer on earth, cellulose is characterized by natural biocompatibility, good mechanical properties, and structure-performance designability. Owing to these outstanding features, cellulose as a biomacromolecule can be designed as functional biomaterials via hydrogen bonding (H-bonding) interaction or chemical modification for human tissue repair, implantable tissue organs, and controlling drug release. Moreover, cellulose can also be used to construct medical sensors for monitoring human physiological signals. In this study, the structural characteristics, functionalization approaches, and advanced biomedical applications of cellulose are reviewed. The current status and application prospects of cellulose and its functional materials for wound dressings, drug delivery, tissue engineering, and electronic skin (e-skin) are discussed. Finally, the key technologies and methods used for designing cellulosic biomaterials and broadening their application prospects in biomedical fields are highlighted.

Celastrol ameliorates experimental autoimmune uveitis through STAT3 targeting and gut microenvironment reprofiling.

BACKGROUND: Extensive research has revealed the favorable effects of celastrol (CEL) against various diseases, but the role of CEL in autoimmune uveitis remains unexplored. METHODS: We first assessed the prophylactical and therapeutical effects of CEL on autoimmune uveitis via rat experimental autoimmune uveitis model. After network pharmacology, functional enrichment and molecular docking analyses, we predicted the potential target of CEL and validated its effect on EAU by clinical and histopathological scores, Evans blue staining, immunofluorescence assay and western blotting. Then we evaluated the role of CEL in the gut environment by 16S rRNA sequencing and untargeted metabolomic analysis. RESULTS: We confirmed that CEL treatment suppressed the pathological TH17 response, inhibited the migration of inflammatory cells, and preserved the integrity of BRB via targeting STAT3-IL17 pathway. Furthermore, CEL was found to reduce the relative abundance of opportunistic pathogenic bacteria including Clostridium_sensu_stricto_1, Parasutterella and GCA-900066575, and enrich the relative abundance of beneficial Oscillospirales and Ruminococcus_torques_group in EAU rats by fecal 16S rRNA sequencing. Meanwhile, CEL treatment reshaped the gut metabolites in the EAU rats by increasing the relative concentrations of cholic acid, progesterone and guggulsterone, and decreasing the relative levels of isoproterenol, creatinine and phenylacetylglutamine. CONCLUSIONS: CEL exerts its ameliorative effects on the experimental autoimmune uveitis through the dual mechanisms of targeting STAT3 and reprofiling the gut microenvironment.

17ß-Estradiol inhibits hydrogen peroxide-induced senescence and apoptosis in human umbilical vein endothelial cells by regulating the THBS1/TGF-ß/Smad axis.

Before menopause, females exhibit a lower incidence of cardiovascular disease than age-matched males, possibly owing to the protective effects of sex hormones. 17ß-estradiol (17ß-E2) protects against oxidative stress-induced injury by suppressing thrombospondin-1 (THBS1) expression in endothelial cells. Here, we examined the role of 17ß-E2-mediated THBS1 suppression in preventing cell senescence and apoptosis. Human umbilical vein endothelial cells (HUVECs) were cultivated and treated with siRNA or overexpression plasmids to regulate THBS1. H2O2, estrogen-activity modulating drugs, and LY2109761 (a TGF-ß kinase inhibitor) treatments were applied. THBS1 knockdown repressed, and its overexpression aggravated, H2O2-induced cell injury, affecting cell death, proliferation, senescence, and apoptosis. 17ß-E2 inhibited THBS1 mRNA and protein expression time- and dose-dependently, by targeting ERß. THBS1 overexpression blocked 17ß-E2 from preventing H2O2-induced injury, significantly activating the TGF-ß/Smad pathway. 17ß-E2 inhibited H2O2-induced oxidative stress by downregulating THBS1 expression and TGF-ß/Smad signaling in HUVECs. The THBS1/TGF-ß/Smad axis could thus be a therapeutic target.

RNA interference of Aspergillus flavus in response to Aspergillus flavus partitivirus 1 infection.

RNA interference (RNAi) is one of the important defense responses against viral infection, but its mechanism and impact remain unclear in mycovirus infections. In our study, reverse genetics and virus-derived small RNA sequencing were used to show the antiviral responses of RNAi components in Aspergillus flavus infected with Aspergillus flavus partitivirus 1 (AfPV1). qRT-PCR revealed that AfPV1 infection induced the expression of the RNAi components in A. flavus compared with noninfected A. flavus. Knock mutants of each RNAi component were generated, but the mutants did not exhibit any obvious phenotypic changes compared with the A. flavus parental strain. However, after AfPV1 inoculation, production of AfPV1 was significantly less than in the parental strain. Furthermore, sporulation was greater in each AfPV1-infected mutant compared with the AfPV1-infected parental A. flavus. We also investigated the sensitivity of virus-free and AfPV1-infected RNAi mutants and the parental strain to cell wall stress, osmotic stress, genotoxic stress, and oxidative stress. The mutants of DCLs and AGOs infected by AfPV1 displayed more changes than RDRP mutants in response to the first three stresses. Small RNA sequencing analysis suggested that AfPV1 infection reduced the number of unique reads of sRNA in A. flavus, although there were many vsiRNA derived from the AfPV1 genome. GO term and KEGG pathway analyses revealed that the functions of sRNA affected by AfPV1 infection were closely related to vacuole production. These results provide a better understanding of the functional role of RNAi in the impact of AfPV1 on the hypovirulence of A. flavus.

Associations between maternal occupational exposures and pregnancy outcomes among Chinese nurses: a nationwide study.

BACKGROUND: Several studies have provided evidence about adverse pregnancy outcomes of nurses involved in occupational exposure. However, the pregnancy outcomes among nurses in middle-income countries are not well demonstrated. The main aim of this study is to present the prevalence and influencing factors of pregnancy outcomes among female nurses in China. METHODS: We included 2243 non-nurse health care workers, and 4230 nurses in this national cross-sectional study in China. Information on occupational exposures and pregnancy outcomes was collected using a face-to-face investigation. Odds ratios (ORs) were estimated through logistic regression. RESULTS: The proportion of threatened abortion, spontaneous abortion, and stillbirth of female nurses was 2.6%, 7%, and 2.1%, respectively. We found an increased risk of threatened abortion among nurses with overtime work (OR = 1.719, 95% CI 1.158-2.550). The risk of threatened abortion and spontaneous abortion was elevated among nurses handling disinfectant (OR = 2.293 and 1.63, respectively). We found a nearly twofold increased risk of premature birth (OR = 2.169, 95% CI 1.36-3.459) among nurses handling anti-cancer drugs. CONCLUSIONS: Our findings suggested that maternal occupational exposures might be associated with the risk of adverse pregnancy outcomes among female nurses in China. We recommend that policy-markers and hospital managers work together to reduce exposure to occupational hazards and improve pregnancy outcomes among female nurses.

Development and validation of a predictive model of abnormal uterine bleeding associated with ovulatory dysfunction: a case-control study.

BACKGROUND: Abnormal uterine bleeding associated with ovulatory dysfunction (AUB-O) is a typical gynecological disease that can affect women of various ages. Being able to identify women at risk of AUB-O could allow physicians to take timely action. This study aimed to identify the influencing factors of AUB-O in Chinese women, and then develop and validate a predictive model. METHODS: In this multicenter case-control study, 391 women with AUB-O and 838 controls who came from nine hospitals in Zhejiang province were recruited between April 2019 and January 2022. All the participants completed a structured questionnaire including general characteristics, lifestyle and habits, menstrual and reproductive history, and previous diseases. The predictive model was developed on a group of 822 women and validated on a group of 407 women. Logistic regression was adopted to investigate the influencing factors and develop the model, and validation was then performed. RESULTS: The independent predictive factors of AUB-O were age (OR 1.073, 95% CI 1.046-1.102, P < 0.001), body mass index (OR 1.081, 95% CI 1.016-1.151, P = 0.015), systolic blood pressure (OR 1.016, 95% CI 1.002-1.029, P = 0.023), residence (OR 2.451, 95% CI 1.727-3.478, P < 0.001), plant-based diet (OR 2.306, 95% CI 1.415-3.759, P < 0.001), fruits eating (OR 1.887, 95% CI 1.282-2.776, P = 0.001), daily sleep duration (OR 0.819; 95% CI 0.708-0.946, P = 0.007), multiparous (parity = 1, OR 0.424, 95% CI 0.239-0.752, P = 0.003; parity > 1, OR 0.450, 95% CI 0.247-0.822, P = 0.009), and history of ovarian cyst (OR 1.880, 95% CI 1.305-2.710, P < 0.001). The predictive ability (area under the curve) in the development group was 0.77 (95% CI 0.74-0.81), while in the validation group it was 0.73 (95% CI 0.67-0.79). The calibration curve was in high coincidence with the standard curve in the development group, and similar to the validation group. A tool for AUB-O risk calculation was created. CONCLUSIONS: Nine influencing factors and a predictive model were proposed in this study, which could identify women who are at high risk of developing AUB-O. This finding highlights the importance of early screening and the lifelong management of ovulatory disorders for women.

ER translocon inhibitor ipomoeassin F inhibits triple-negative breast cancer growth via blocking ER molecular chaperones.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer where no effective therapy has been developed. Here, we report that the natural product ER translocon inhibitor ipomoeassin F is a selective inhibitor of TNBC cell growth. A proteomic analysis of TNBC cells revealed that ipomoeassin F significantly reduced the levels of ER molecular chaperones, including PDIA6 and PDIA4, and induced ER stress, unfolded protein response (UPR) and autophagy in TNBC cells. Mechanistically, ipomoeassin F, as an inhibitor of Sec61α-containing ER translocon, blocks ER translocation of PDIA6, inducing its proteasomal degradation. Silencing of PDIA6 or PDIA4 by RNA interferences or treatment with a small molecule inhibitor of the protein disulfide isomerases in TNBC cells successfully recapitulated the ipomoeassin F phenotypes, including the induction of ER stress, UPR and autophagy, suggesting that the reduction of PDIAs is the key mediator of the pharmacological effects of ipomoeassin F. Moreover, ipomoeassin F significantly suppressed TNBC growth in a mouse tumor xenograft model, with a marked reduction in PDIA6 and PDIA4 levels in the tumor samples. Our study demonstrates that Sec61α-containing ER translocon and PDIAs are potential drug targets for TNBC and suggests that ipomoeassin F could serve as a lead for developing ER translocon-targeted therapy for TNBC.

A high linearity and multilevel polymer-based conductive-bridging memristor for artificial synapses.

Conductive-bridging memristors based on a metal ion redox mechanism have good application potential in future neuromorphic computing nanodevices owing to their high resistance switch ratio, fast operating speed, low power consumption and small size. Conductive-bridging memristor devices rely on the redox reaction of metal ions in the dielectric layer to form metal conductive filaments to control the conductance state. However, the migration of metal ions is uncontrollable by the applied bias, resulting in the random generation of conductive filaments, and the conductance state is difficult to accurately control. Herein, we report an organic polymer carboxylated chitosan-based memristor doped with a small amount of the conductive polymer PEDOT:PSS to improve the polymer ionic conductivity and regulate the redox of metal ions. The resulting device exhibits uniform conductive filaments during device operation, more than 100 and non-volatile conductance states with a ∼1 V range, and linear conductance regulation. Moreover, simulation using handwritten digital datasets shows that the recognition accuracy of the carboxylated chitosan-doped PEDOT:PSS memristor array can reach 93%. This work provides a path to facilitate the performance of metal ion-based memristors in artificial synapses.

Complete genome sequence of a novel chrysovirus infecting Aspergillus terreus.

A double-stranded RNA (dsRNA) mycovirus was obtained from Aspergillus terreus strain HJ3-26 and designated "Aspergillus terreus chrysovirus 1" (AtCV1). It consists of four dsRNA segments (dsRNA1-4) with lengths of 3612 bp, 3132 bp, 3153 bp, and 3144 bp, respectively. Sequence analysis showed that dsRNA1 encodes an RNA-dependent RNA polymerase (RdRp), dsRNA2 encodes a capsid protein, and both dsRNA3 and dsRNA4 encode hypothetical proteins. Phylogenetic analysis of the RdRp suggested that AtCV1 is a member of a new species of the genus Alphachrysovirus in the family Chrysoviridae. This is the first chrysovirus obtained from A. terreus.

Global, regional, and national time trends in incidence, prevalence, years lived with disability for uterine fibroids, 1990-2019: an age-period-cohort analysis for the global burden of disease 2019 study.

BACKGROUND: Uterine fibroids are the most common benign neoplasm of the uterus and a major source of morbidity for women. We report an overview of trends in uterine fibroids of incidence rate, prevalence rate, years lived with disability (YLDs) rate in 204 countries and territories over the past 30 years and associations with age, period, and birth cohort. METHODS: The incident case, incidence rate, age-standardized rate (ASR) for incidence, prevalent case, prevalence rate, ASR for prevalence, number of YLDs, YLD rate, and ASR for YLDs were derived from the Global Burden of Disease 2019 (GBD 2019) study. We utilized an age-period-cohort (APC) model to estimate overall annual percentage changes in the rate of incidence, prevalence, and YLDs (net drifts), annual percentage changes from 10 to 14 years to 65-69 years (local drifts), period and cohort relative risks (period/cohort effects) between 1990 and 2019. RESULTS: Globally, the incident cases, prevalent cases, and the number of YLDs of uterine fibroids increased from 1990 to 2019 with the growth of 67.07%, 78.82% and 77.34%, respectively. High Socio-demographic Index (SDI) and high-middle SDI quintiles with decreasing trends (net drift < 0.0%), and increasing trends (net drift > 0.0%) were observed in middle SDI, low-middle SDI, and low SDI quintiles in annual percentage change of incidence rate, prevalence rate and YLDs rate over the past 30 years. There were 186 countries and territories that showed an increasing trend in incidence rate, 183 showed an increasing trend in prevalence rate and 174 showed an increasing trend in YLDs rate. Moreover, the effects of age on uterine fibroids increased with age and peaked at 35-44 years and then declined with advancing age. Both the period and cohort effects on uterine fibroids showed increasing trend in middle SDI, low-middle SDI and low SDI quintiles in recent 15 years and birth cohort later than 1965. CONCLUSIONS: The global burden of uterine fibroids is becoming more serious in middle SDI, low-middle SDI and low SDI quintiles. Raising awareness of uterine fibroids, increasing medical investment and improving levels of medical care are necessary to reduce future burden.

In utero bisphenol A exposure disturbs germ cell cyst breakdown through the PI3k/Akt signaling pathway and BDNF expression.

PURPOSE: To determine the influence of the environmental endocrine disruptor bisphenol A (BPA) on germ cell cyst breakdown and explore the possible mechanisms regulating this activity. METHODS: BPA (2 µg/kg/d or 20 µg/kg/d) or tocopherol-stripped corn oil (vehicle control) was administered to pregnant mice by gavage at gestational day 11, and the offspring (prenatally treated mice) were sacrificed and ovariectomized at postnatal day (PND) 4 and PND22. Ovarian morphology was documented in the first filial (F1) generation female offspring, and the follicles were analyzed and classified morphologically on PND 4. To discover differentially expressed genes and associated target pathways, we used RNA-seq, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis, and Gene Ontology (GO) analysis. The mRNA expression of key steroid hormone synthesis-related genes was evaluated by Q-PCR in forskolin-induced KGN cells. Western blotting (WB) and qRTPCR were used to determine the protein and gene expression levels of brain-derived neurotrophic factor (BDNF). RESULTS: BPA, a typical endocrine disrupting chemical (EDC), decreased the expression of the key steroid hormone synthesis-related genes P450scc and aromatase, while the expression of Star increased significantly and caused no significant difference in the expression of Cyp17a1 or HSD3ß in forskolin-induced KGN cells. Moreover, we confirmed that in utero exposure to environmentally relevant concentrations of BPA (2 µg/kg/d and 20 µg/kg/d) could significantly disrupt germ cell cyst breakdown, leading to the generation of fewer primordial follicles than in the control group. The factors mediating the inhibitory effects included the PI3K-Akt signaling pathway and a significant downregulation of BDNF. CONCLUSIONS: These findings indicate that in utero exposure to BPA at low doses, which are lower than recommended as 'safe' dosages, may influence the formation of primordial follicles by inhibiting the expression of steroid hormone synthesis-related genes and partly by regulating the BDNF-mediated PI3K/Akt pathway.

Lateral septum adenosine A2A receptors control stress-induced depressive-like behaviors via signaling to the hypothalamus and habenula.

Major depressive disorder ranks as a major burden of disease worldwide, yet the current antidepressant medications are limited by frequent non-responsiveness and significant side effects. The lateral septum (LS) is thought to control of depression, however, the cellular and circuit substrates are largely unknown. Here, we identified a subpopulation of LS GABAergic adenosine A2A receptors (A2AR)-positive neurons mediating depressive symptoms via direct projects to the lateral habenula (LHb) and the dorsomedial hypothalamus (DMH). Activation of A2AR in the LS augmented the spiking frequency of A2AR-positive neurons leading to a decreased activation of surrounding neurons and the bi-directional manipulation of LS-A2AR activity demonstrated that LS-A2ARs are necessary and sufficient to trigger depressive phenotypes. Thus, the optogenetic modulation (stimulation or inhibition) of LS-A2AR-positive neuronal activity or LS-A2AR-positive neurons projection terminals to the LHb or DMH, phenocopied depressive behaviors. Moreover, A2AR are upregulated in the LS in two male mouse models of repeated stress-induced depression. This identification that aberrantly increased A2AR signaling in the LS is a critical upstream regulator of repeated stress-induced depressive-like behaviors provides a neurophysiological and circuit-based justification of the antidepressant potential of A2AR antagonists, prompting their clinical translation.

Antibacterial coatings on orthopedic implants.

With the aging of population and the rapid improvement of public health and medical level in recent years, people have had an increasing demand for orthopedic implants. However, premature implant failure and postoperative complications frequently occur due to implant-related infections, which not only increase the social and economic burden, but also greatly affect the patient's quality of life, finally restraining the clinical use of orthopedic implants. Antibacterial coatings, as an effective strategy to solve the above problems, have been extensively studied and motivated the development of novel strategies to optimize the implant. In this paper, a variety of antibacterial coatings recently developed for orthopedic implants were briefly reviewed, with the focus on the synergistic multi-mechanism antibacterial coatings, multi-functional antibacterial coatings, and smart antibacterial coatings that are more potential for clinical use, thereby providing theoretical references for further fabrication of novel and high-performance coatings satisfying the complex clinical needs.

Identification of MKNK1 and TOP3A as ovarian endometriosis risk-associated genes using integrative genomic analyses and functional experiments.

The risk of endometriosis (EM), which is a common complex gynaecological disease, is related to genetic predisposition. However, it is unclear how genetic variants confer the risk of EM. Here, via Sherlock integrative analysis, we combined large-scale genome-wide association studies (GWAS) summary statistics on EM (N = 245,494) with a blood-based eQTL dataset (N = 1490) to identify EM risk-related genes. For validation, we leveraged two independent eQTL datasets (N = 769) for integration with the GWAS data. Thus, we prioritised 14 genes, including GIMAP4, TOP3A, and NMNAT3, which showed significant association with susceptibility to EM. We also utilised two independent methods, Multi-marker Analysis of GenoMic Annotation and S-PrediXcan, to further validate the EM risk-associated genes. Moreover, protein-protein interaction network analysis showed the 14 genes were functionally connected. Functional enrichment analyses further demonstrated that these genes were significantly enriched in metabolic and immune-related pathways. Differential gene expression analysis showed that in peripheral blood samples from patients with ovarian EM, TOP3A, MKNK1, SIPA1L2, and NUCB1 were significantly upregulated, while HOXB2, GIMAP5, and MGMT were significantly downregulated compared with their expression levels in samples from the controls. Immunohistochemistry further confirmed the increased expression levels of MKNK1 and TOP3A in the ectopic and eutopic endometrium compared to normal endometrium, while HOBX2 was downregulated in the endometrium of women with ovarian EM. Finally, in ex vivo functional experiments, MKNK1 knockdown inhibited ectopic endometrial stromal cells (EESCs) migration and invasion. TOP3A knockdown inhibited EESCs proliferation, migration, and invasion, while promoting their apoptosis. Convergent lines of evidence suggested that MKNK1 and TOP3A are novel EM risk-related genes.

Development and Validation of a Nomogram Prediction Model for Endometrial Malignancy in Patients with Abnormal Uterine Bleeding.

PURPOSE: This study aimed to identify the risk factors and sonographic variables that could be integrated into a predictive model for endometrial cancer (EC) and atypical endometrial hyperplasia (AEH) in women with abnormal uterine bleeding (AUB). MATERIALS AND METHODS: This retrospective study included 1837 patients who presented with AUB and underwent endometrial sampling. Multivariable logistic regression was developed based on clinical and sonographic covariates [endometrial thickness (ET), resistance index (RI) of the endometrial vasculature] assessed for their association with EC/AEH in the development group (n=1369), and a predictive nomogram was proposed. The model was validated in 468 patients. RESULTS: Histological examination revealed 167 patients (12.2%) with EC or AEH in the development group. Using multivariable logistic regression, the following variables were incorporated in the prediction of endometrial malignancy: metabolic diseases [odds ratio (OR)=7.764, 95% confidence intervals (CI) 5.042-11.955], family history (OR=3.555, 95% CI 1.055-11.971), age ≥40 years (OR=3.195, 95% CI 1.878-5.435), RI ≤0.5 (OR=8.733, 95% CI 4.311-17.692), and ET ≥10 mm (OR=8.479, 95% CI 5.440-13.216). A nomogram was created using these five variables with an area under the curve of 0.837 (95% CI 0.800-0.874). The calibration curve showed good agreement between the observed and predicted occurrences. For the validation group, the model provided acceptable discrimination and calibration. CONCLUSION: The proposed nomogram model showed moderate prediction accuracy in the differentiation between benign and malignant endometrial lesions among women with AUB.