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Abstract Background It has been reported that age-associated cognitive decline (AACD) accelerated by maternal lipopolysaccharide (LPS) insult during late pregnancy can be transmitted to the second generation in a sex-specificity manner. In turn, recent studies indicated that glial cell line‐derived neurotrophic factor (GDNF) and its cognate receptor (GFRα1) are critical for normal cognitive function. Based on this evidence, we aimed to explore whether Gdnf-GFRα1 expression contributes to cognitive decline in the F1 and F2 generations of mouse dams exposed to lipopolysaccharide (LPS) during late gestation, and to evaluate also the potential interference effect of pro-inflammatory cytokines. Methods During gestational days 15–17, pregnant CD-1 mice (8–10 weeks old) received a daily intraperitoneal injection of LPS (50 μg/kg) or saline (control). In utero LPS-exposed F1 generation mice were selectively mated to produce F2 generation mice. In F1 and F2 mice aged 3 and 15 months, the Morris water maze (MWM) was used to evaluated the spatial learning and memory ability, the western blotting and RT-PCR were used for analyses of hippocampal Gdnf and GFRα1 expression, and ELISA was used to analyse IL-1β, IL-6 and TNF-α levels in serum. Results Middle-aged F1 offspring from LPS-treated mothers exhibited longer swimming latency and distance during the learning phase, lower percentage swimming time and distance in targe quadrant during memory phase, and lower hippocampal levels of Gdnf and GFRα1 gene products compared to age-matched controls. Similarly, the middle-aged F2 offspring from the Parents-LPS group had longer swimming latency and distance in the learning phase, and lower percentage swimming time and distance in memory phase than the F2-CON group. Moreover, the 3-month-old Parents-LPS and 15-month-old Parents- and Father-LPS groups had lower GDNF and GFRα1 protein and mRNAs levels compared to the age-matched F2-CON group. Furthermore, hippocampal levels of Gdnf and GFRα1 were correlated with impaired cognitive performance in the Morris water maze after controlling for circulating pro-inflammatory cytokine levels. Conclusions Our findings indicate that accelerated AACD by maternal LPS exposure can be transmitted across at least two generations through declined Gdnf and GFRα1 expression, mainly via paternal linage.

Accurate numerical prediction of frosting patterns is essential for the efficient layout and timing defrosting of heat exchangers under frosting conditions. In this study, a numerical model is developed to predict the spatio-temporal frosting habits on curved surfaces in combination with the correlations of frost density and thermal conductivity. In the model, frost melting is considered. After verification, the frosting and heat transfer characteristics along the flow path are investigated under various structural and operating conditions. Frost thickness along the path is mainly affected by the cooling surface temperature, while the heat and mass transfer rates are strongly correlated with the humidity ratio. The proportions of latent heat and sensible heat are distributed more unevenly in parallel flow case than in counter flow case. Frost deposition is facilitated by a smaller radius of curvature of the cooling surface. More uniform frosting characteristics along the path and smaller heat transfer obstruction are presented with a smaller length-to-height ratio of the flow path.

Betanin is a member of natural pigment betacyanins family and has extensive application in the food industry as an important natural red food colorant. Its relatively inefficient production in nature however hampers access to this phytochemicals through traditional crop-based manufacturing. Microbial bioproduction therefore represents an attractive alternative. Here, we present the construction of a Saccharomyces cerevisiae strain for betanin production. Through minimizing metabolic crosstalk, screening and modifying biosynthetic enzymes, enhancing pathway flux and optimizing fermentation conditions, a final titer of betanin of 28.7 mg/L was achieved from glucose at 25 °C in baffled shake-flask, which is the highest reported titer produced by yeast to our knowledge. This work provides a promising step towards developing synthetic yeast cell factories for de novo biosynthesis of value-added betanin and other betacyanins.

Micro-Doppler time–frequency analysis has been regarded as an important parameter extraction method for conical micro-motion objects. However, the micro-Doppler effect caused by micro-motion can modulate the frequency of lidar echo, leading to coupling between structure and micro-motion parameters. Therefore, it is difficult to extract parameters for micro-motion cones. We propose a new method for parameter extraction by combining the range profile of a micro-motion cone and the micro-Doppler time–frequency spectrum. This method can effectively decouple and accurately extract the structure and the micro-motion parameters of cones. Compared with traditional time–frequency analysis methods, the accuracy of parameter extraction is higher, and the information is richer. Firstly, the range profile of the micro-motion cone was obtained by using an FMCW (Frequency Modulated Continuous Wave) lidar based on simulation. Secondly, quantitative analysis was conducted on the edge features of the range profile and the micro-Doppler time–frequency spectrum. Finally, the parameters of the micro-motion cone were extracted based on the proposed decoupling parameter extraction method. The results show that our method can effectively extract the cone height, the base radius, the precession angle, the spin frequency, and the gravity center height within the range of a lidar LOS (line of sight) angle from 20° to 65°. The average absolute percentage error can reach below 10%. The method proposed in this paper not only enriches the detection information regarding micro-motion cones, but also improves the accuracy of parameter extraction and establishes a foundation for classification and recognition. It provides a new technical approach for laser micro-Doppler detection in accurate recognition.

The construction of heterojunction is an effective way to promote the photoinduced charge carrier separation in spatial, thus accelerating the photocatalytic reaction. However, the regulation of interface properties, as a crucial factor in affecting the charge carrier diffusion process, still remains a significant challenge. In this work, BiOBr/TpBD-COF heterojunction was successfully constructed via a novel phase transformation strategy. Specifically, perovskite Cs3Bi2Br9 was first synthesized and then in-situ transformed into BiOBr during the preparation of TpBD-COF procedure, thus obtaining BiOBr/TpBD-COF heterojunction with favorable interface. According to the in-situ X-ray photoelectron spectroscopy (XPS) characterization and electron paramagnetic resonance (EPR) analysis, the photogenerated electrons with weak reduction power transfer from BiOBr to TpBD-COF driven by the internal electric field under irradiation, conforming to S-scheme charge transfer mode. As a result, the photogenerated electrons and holes with strong redox abilities are spatially located on TpBD-COF and BiOBr surface, respectively, endowing the strong driving force toward the water splitting reaction. The optimized 10%BiOBr/TpBD-COF displayed remarkably enhanced photocatalytic hydrogen evolution rate (16.17 mmol⋅g−1⋅h−1) in comparison with TpBD-COF (5.18 mmol⋅g−1⋅h−1). This study will provide some novel inspirations for developing efficient COF-based S-scheme heterojunction photocatalysts.

Abstract Melittin, the principal constituent in bee venom, is an attractive candidate for cancer therapy. However, its clinical applications are limited by hemolysis, nonspecific cytotoxicity, and rapid metabolism. Herein, a novel genetically engineered vesicular antibody‐melittin (VAM) drug delivery platform was proposed and validated for targeted cancer combination therapy. VAM generated from the cellular plasma membrane was bio‐synthetically fabricated, with the recombinant protein (hGC33 scFv‐melittin) being harbored and displayed on the cell membrane. The bioactive and targetable nanomelittin conjugated by hGC33 scFv could be released in an MMP14‐responsive manner at tumor sites, which reduced off‐target toxicity, especially the hemolytic activity of melittin. Importantly, VAM could be loaded with small‐molecule drugs or nanoparticles for combination therapy. Nanomelittin formed pores in membranes and disturbed phospholipid bilayers, which allowed the anticancer agents (i.e., chemotherapeutic drug doxorubicin and sonosensitizer purpurin 18 nanoparticles) co‐delivered by VAM to penetrate deeper tumor sites, leading to synergistic therapeutic effects. In particular, the punching effect generated by sonodynamic therapy further improved the immunomodulatory effect of nanomelittin to activate the immune response. Taken together, our findings indicate that clinically translatable VAM‐based strategies represent a universal, promising approach to multimodal synergetic cancer therapy.

ObjectiveThis retrospective analysis aims to assess the efficacy of transesophageal ultrasound-guided patent foramen ovale (PFO) closure in treating migraine in adolescents and compare the therapeutic outcomes of PFO closure for migraine with and without aura.MethodsWe conducted a retrospective analysis of 86 cases of adolescents (12–20 years old) who underwent PFO closure for migraine at our institution over the past 3 years. The efficacy was evaluated using the visual analogue scale (VAS), headache impact test (HIT)-6, and pediatric migraine disability assessment (PedMIDAS) scores, as well as by assessing the monthly frequency of migraine attacks, duration of each attack, and overall migraine burden. The patients were divided into two groups: an aura group (55 cases) and a non-aura group (31 cases) to investigate difference in therapeutic efficacy between the groups. The effect of residual shunt on migraine burden was assessed.ResultsAmong the 86 patients, 46 (54%) experienced complete remission of migraine, while 71 (83%) achieved a >50% reduction in migraine burden during the one-year follow-up period. Patients in the aura group showed more significant improvements in VAS, HIT-6, and PedMIDAS scores, as well as in monthly migraine attack frequency, duration of each attack, and overall migraine burden, than patients in the non-aura group. Moreover, patients with residual shunt did not exhibit statistically significant differences in therapeutic efficacy compared to patients with complete closure.ConclusionPFO closure can effectively alleviate migraine symptoms in adolescents with migraine with concomitant PFO. The therapeutic efficacy is particularly pronounced for migraine with aura. Furthermore, minor levels of residual shunt have no effect on the improvement in migraine symptoms.

BackgroundCuproptosis, the most recently identified and regulated cell death, depends on copper ions in vivo. Copper regulates the pathogenesis of Idiopathic pulmonary fibrosis (IPF), but the mechanism of action underlying cuproptosis in IPF remains unclear.MethodsWe identified three cuproptosis patterns based on ten cuproptosis-related genes using unsupervised consensus clustering. We quantified these patterns using a PCA algorithm to construct a cuproptosis score. ssGSEA and the Cibersort algorithm assessed the immune profile of IPF patients. GSEA and GSVA were used to analyze the functional differences in different molecular patterns. Drug susceptibility prediction based on cuproptosis scores and meaningful gene markers was eventually screened in combination with external public data sets,in vitro experiments and our cases.ResultsOf the three types of cuproptosis-related clusters identified in the study, patients in the clusterA, geneclusterB, and score-high groups showed improved prognoses. Moreover, each cluster exhibited differential immune characteristics, with the subtype showing a poorer prognosis associated with an immune overreaction. Cuproptosis score can be an independent risk factor for predicting the prognosis of IPF patients. GSEA showed a significant functional correlation between the score and cuproptosis. The genes AKAP9, ANK3, C6orf106, LYRM7, and MBNL1, were identified as prognostic-related signatures in IPF patients. The functional role of immune regulation in IPF was further explored by correlating essential genes with immune factors. Also, the nomogram constructed by cumulative information from gene markers and cuproptosis score showed reliable clinical application.ConclusionsCuproptosis patterns differ significantly in the prognosis and immune characteristics of IPF patients. The cuproptosis score and five gene signatures can provide a reliable reference in the prognosis and diagnosis of IPF.

Drug therapy, including chemotherapy, targeted therapy, immunotherapy, and endocrine therapy, stands as the foremost therapeutic approach for contemporary human malignancies. However, increasing drug resistance during antineoplastic therapy has become a substantial barrier to favorable outcomes in cancer patients. To enhance the effectiveness of different cancer therapies, an in-depth understanding of the unique mechanisms underlying tumor drug resistance and the subsequent surmounting of antitumor drug resistance is required. Recently, F-box and WD Repeat Domain-containing-7 (FBXW7), a recognized tumor suppressor, has been found to be highly associated with tumor therapy resistance. This review provides a comprehensive summary of the underlying mechanisms through which FBXW7 facilitates the development of drug resistance in cancer. Additionally, this review elucidates the role of FBXW7 in therapeutic resistance of various types of human tumors. The strategies and challenges implicated in overcoming tumor therapy resistance by targeting FBXW7 are also discussed.

Using EnergyPlus software to simulate the energy consumption of residential buildings in Harbin, Beijing, Nanjing, Haikou, and Kunming under various conditions, this study investigated the energy-saving potential of thermal insulating walls constructed with Super Thin Panel (STP). It also examined the benefits and drawbacks of the heat transfer performance of the panels, as well as the potential and viability of using STP as insulation materials. The findings demonstrated that in Harbin, Beijing, and Nanjing, the overall energy consumption for heating, cooling, and air conditioning dropped as the thickness of the insulation layer increased. Haikou had no need for any heating energy, and cooling energy use reduced as insulation thickness grew. In Kunming, the total energy consumption for cooling and air conditioning increased as insulation layer thickness grew while the energy consumption for heating reduced as insulation layer thickness increased. According to the findings, when STP panels is utilized as a thermal insulation material, its thermal insulation effect is remarkable. Under the same thermal insulation effect, the thickness was substantially thinner than that of conventional thermal insulation material. STP implementation had the biggest impact in Harbin, followed by Beijing, and had little influence in Haikou and Kunming, where there was essentially no heating demand. This implies that the use of STP vacuum insulation panels in cold areas of China has a promising future.

Abstract It has been widely recognized that tropical cyclone (TC) genesis requires favorable large‐scale environmental conditions. Based on these linkages, numerous efforts have been made to establish an empirical relationship between seasonal TC activities and large‐scale environmental favorability in a quantitative way, which lead to conceptual functions such as the TC genesis index. However, due to the limited amount of reliable TC observations and complexity of the climate system, a simple analytic function may not be an accurate portrait of the empirical relationship between TCs and their ambiences. In this research, we use convolution neural networks (CNNs) to disentangle this complex relationship. To circumvent the limited amount of seasonal TC observation records, we implement transfer‐learning technique to train ensemble of CNNs first on suites of high‐resolution climate model simulations with realistic seasonal TC activities and large‐scale environmental conditions, and then on a state‐of‐the‐art reanalysis from 1950 to 2019. The trained CNNs can well reproduce the historical TC records and yields significant seasonal prediction skills when the large‐scale environmental inputs are provided by operational climate forecasts. Furthermore, by inputting the ensemble CNNs with 20th century reanalysis products and Phase 6 of the Coupled Model Intercomparison Project (CMIP6) simulations, we investigated TC variability and its changes in the past and future climates. Specifically, our ensemble CNNs project a decreasing trend of global mean TC activity in the future warming scenario, which is consistent with our future projections using high‐resolution climate model.

Background The relationship between mitochondrial DNA copy number (mtDNA CN) and cardiovascular disease remains elusive. Methods and Results We performed cross‐sectional and prospective association analyses of blood‐derived mtDNA CN and cardiovascular disease outcomes in 27 316 participants in 8 cohorts of multiple racial and ethnic groups with whole‐genome sequencing. We also performed Mendelian randomization to explore causal relationships of mtDNA CN with coronary heart disease (CHD) and cardiometabolic risk factors (obesity, diabetes, hypertension, and hyperlipidemia). P

Anti-tumor drug resistance is a challenge for human triple-negative breast cancer (TNBC) treatment. Our previous work demonstrated that TNFAIP2 activates RAC1 to promote TNBC cell proliferation and migration. However, the mechanism by which TNFAIP2 activates RAC1 is unknown. In this study, we found that TNFAIP2 interacts with IQGAP1 and Integrin β4. Integrin β4 activates RAC1 through TNFAIP2 and IQGAP1 and confers DNA damage-related drug resistance in TNBC. These results indicate that the Integrin β4/TNFAIP2/IQGAP1/RAC1 axis provides potential therapeutic targets to overcome DNA damage-related drug resistance in TNBC.

Purpose: To evaluate the ability of multiple dual-phase 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) metabolic parameters to distinguish the histological subtypes of non-small cell lung cancer (NSCLC). Methods: Data from 127 patients with non-small cell lung cancer who underwent preoperative dual-phase 18F-FDG PET/CT scanning at the PET-CT center of our hospital from December 2020 to October 2021 were collected, and the metabolic parameters of their primary lesions were measured and analyzed retrospectively. Intraclass correlation coefficients (ICC) were calculated for consistency between readers. Metabolic parameters in the early (SUVpeak, SUVmean, SUVmin, SUVmax, MTV, and TLG) and delayed phases (dpSUVpeak, dpSUVmean, dpSUVmin, dpSUVmax, dpMTV, and dpTLG) were calculated. We drew receiver operating characteristic (ROC) curves to compare the differences in different metabolic parameters between the adenocarcinoma (AC) and squamous cell carcinoma (SCC) groups and evaluated the ability of different metabolic parameters to distinguish AC from SCC. Results: Inter-reader agreement, as assessed by the intraclass correlation coefficient (ICC), was good (ICC = 0.71, 95% CI:0.60–0.79). The mean MTV, SUVmax, TLG, SUVpeak, SUVmean, dpSUVmax, dpTLG, dpSUVpeak, dpSUVmean, and dpSUVmin of the tumors were significantly higher in SCC lesions than in AC lesions (P = 0.049,

To investigate the function of the cell cycle Cyclin E gene (ccne) in the ovarian development of Exopalaemon carinicauda, the gene was cloned using the RACE technique, and the relative expression of ccne was analyzed in different tissues at different stages of ovarian development. The effect of knocking down the expression of ccne on yolk protein vitellogenin (vg) was also investigated at ovarian developmental stage II using RNAi. The results showed that the full-length cDNA sequence of ccne in E. carinicauda (1692 bp, with a 5′UTR of 127 bp, a 3′UTR of 299 bp, and an ORF of 1266 bp) could encode a total of 421 amino acids, with a predicted protein molecular weight of 48.04 kDa and a theoretical isoelectric point of 6.28. The relative expression of ccne was high during all stages of ovarian development, with the highest expression occurring in stage III. In addition, the phylogenetic tree showed that E. carinicauda and Penaeus monodon were clustered into one branch. Knocking down the ccne expression inhibited the expression of vg, meaning that the expression of ccne and vg were positively correlated. In situ hybridization showed that ccne was abundantly expressed in ova, thus inferring that ccne plays a regulatory role and is involved in nutrient accumulation and transport in the ovaries of E. carinicauda.

Abstract Background This study investigated the efficacy of the integrated blood purification mode of early haemoperfusion (HP) combined with continuous venovenous haemodiafiltration (CVVHDF) in children with severe viral encephalitis, and evaluated the correlation of cerebrospinal fluid (CSF) neopterin (NPT) levels with prognosis. Methods The records of children with viral encephalitis who received blood purification treatment in the authors’ hospital from September 2019 to February 2022 were retrospectively analysed. According to the blood purification treatment mode, they were divided into the experimental group (HP + CVVHDF, 18 cases), control group A (CVVHDF only, 14 cases), and control group B (16 children with mild viral encephalitis who did not receive blood purification treatment). The correlation between the clinical features, severity of the disease and the extent of lesions on brain magnetic resonance imaging (MRI) and the CSF NPT levels was analysed. Results The experimental group and control group A were comparable with respect to age, gender and hospital course (P > 0.05). There was no significant difference in speech and swallowing functions between the two groups after treatment (P > 0.05) and no significant difference in 7 and 14-day mortality (P > 0.05). The CSF NPT levels in the experimental group before treatment were significantly higher compared with control group B (P

Frequency regulation services can be provided by emerging flexible resources such as electric vehicles and energy storage which can rapidly adjust the output in response to regulation signals, as long as there is an effective market to provide proper incentives. However, current regulation markets were designed for conventional thermal generating units, and it is difficult for the mileage-based bidding structure to express the cost characteristics of flexible resources. Therefore, the current mechanisms are not conducive to encouraging the participation of flexible resources in providing frequency regulation services. This paper proposes an incentive-compatible frequency regulation market for flexible resources, whose revisions to the existing mechanism include the bidding structure, clearing rules, and settlement rules that adapt to the characteristics of flexible resources. Compared with the current mechanism, the proposed mechanism can reduce the costs of deploying regulation and more reasonably allocate the revenues for regulation services. The case studies verify the effectiveness of the proposed mechanism.

The mechanisms behind how vascular repair is regulated after ischemic stroke are yet to be elucidated. Here, the authors describe that a circular RNA interacts with FTO to promote vascular repair following stroke in mice and primates via mediating m6 A modification.

Abstract Background Enhanced recovery after surgery (ERAS) is now widely used in various surgical fields including gynecological laparoscopic surgery, but the advantages of opioid-free anesthesia (OFA) in gynecological laparoscopic surgery under ERAS protocol are inexact. Aims This study aims to assess the effectiveness and feasibility of OFA technique versus traditional opioid-based anesthesia (OA) technique in gynecological laparoscopic surgery under ERAS. Methods Adult female patients aged 18 ~ 65 years old undergoing gynecological laparoscopic surgery were randomly divided into OFA group (Group OFA, n = 39) with esketamine and dexmedetomidine or OA group (Group OA, n = 38) with sufentanil and remifentanil. All patients adopted ERAS protocol. The primary outcome was the area under the curve (AUC) of Visual Analogue Scale (VAS) scores (AUCVAS) postoperatively. Secondary outcomes included intraoperative hemodynamic variables, awakening and orientation recovery times, number of postoperative rescue analgesia required, incidence of postoperative nausea and vomiting (PONV) and Pittsburgh Sleep Quality Index (PSQI) perioperatively. Results AUCVAS was (Group OFA, 16.72 ± 2.50) vs (Group OA, 15.99 ± 2.72) (p = 0.223). No difference was found in the number of rescue analgesia required (p = 0.352). There were no between-group differences in mean arterial pressure (MAP) and heart rate (HR) (p = 0.211 and 0.659, respectively) except MAP at time of surgical incision immediately [(Group OFA, 84.38 ± 11.08) vs. (Group OA, 79.00 ± 8.92), p = 0.022]. Times of awakening and orientation recovery in group OFA (14.54 ± 4.22 and 20.69 ± 4.92, respectively) were both longer than which in group OA (12.63 ± 3.59 and 18.45 ± 4.08, respectively) (p = 0.036 and 0.033, respectively). The incidence of PONV in group OFA (10.1%) was lower than that in group OA (28.9%) significantly (p = 0.027). The postoperative PSQI was lower than the preoperative one in group OFA (p = 0.013). Conclusion In gynecological laparoscopic surgery under ERAS protocol, OFA technique is non-inferior to OA technique in analgesic effect and intraoperative anesthesia stability. Although awakening and orientation recovery times were prolonged compared to OA, OFA had lower incidence of PONV and improved postoperative sleep quality. Trial registration ChiCTR2100052761, 05/11/2021.

Abstract Background To predict and validate the potential mechanism by which Gynura divaricata (GD) functions in the treatment of diabetic foot (DF). Methods The main chemical constituents of GD were identified by reviewing the literature, the traditional Chinese medicine database platform (TCMIP) and the BATMAN-TCM platform. DF disease targets were identified with the GeneCards database, and the compound-target network was constructed by using the intersection of drugs and disease. The STRING platform was used to construct the protein–protein interaction (PPI) network, and Cytoscape 3.7.2 software was used to visualize the results. Moreover, the Metascape database was used for Gene Ontology (GO) enrichment analyses and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses. Molecular docking of the active ingredients of GD and core protein targets of DF was performed using AutoDock software. Finally, the predicted results were preliminarily verified with experiments. Results A total of 140 potential targets of GD were identified and associated with DF. According to the PPI network analysis, GD accelerated DF wound healing, and the mechanism may be related to proteins such as AKT1, TP53, IL6, CASP3, TNF, and VEGFA. GO and KEGG enrichment analyses indicated that GD may play a role in the treatment of diabetic foot by affecting various signaling pathways. Molecular docking results showed that the proteins AKT1, TP53, IL6, CASP3, TNF, and VEGFA were closely associated with the components of GD. The animal experiments showed that GD reduced the levels of IL-6 and TNF-α and increased the mRNA and protein expression of VEGFA in rats with DF. Conclusions GD regulates multiple targets and multiple pathways to promote wound healing in DF.

Abstract Background Sex differences ranging from physiological functions to pathological disorders are developmentally hard-wired in a broad range of animals, from invertebrates to humans. These differences ensure that animals can display appropriate behaviors under a variety of circumstances, such as aggression, hunting, sleep, mating, and parental care, which are often thought to be important in the acquisition of resources, including territory, food, and mates. Although there are reports of an absence of sexual dimorphism in the context of innate fear, the question of whether there is sexual dimorphism of innate defensive behavior is still an open question. Therefore, an in-depth investigation to determine whether there are sex differences in developmentally hard-wired innate defensive behaviors in life-threatening circumstances is warranted. Results We found that innate defensive behavioral responses to potentially life-threatening stimuli between males and females were indistinguishable over their lifespan. However, by using 3 dimensional (3D)-motion learning framework analysis, we found that males and females showed different behavioral patterns after escaping to the refuge. Specifically, the defensive “freezing” occurred primarily in males, whereas females were more likely to return directly to exploration. Moreover, there were also no estrous phase differences in innate defensive behavioral responses after looming stimuli. Conclusions Our results demonstrate that visually-evoked innate fear behavior is highly conserved throughout the lifespan in both males and females, while specific post-threat coping strategies depend on sex. These findings indicate that innate fear behavior is essential to both sexes and as such, there are no evolutionary-driven sex differences in defensive ability.

Abstract Owing to the need for regenerant and self‐reduction problem, the hydrogen performance of sub‐nano‐sized trinuclear iron‐oxo complexes is still far from satisfied with affordability and practicality. Herein, two binary photocatalytic systems based on trinuclear metal‐oxo complexes have been first constructed and experimentally confirmed to be competent for seawater hydrogen evolution (715.4 and 271.9 μmol of hydrogen can be found, respectively, after 48 h). Notably, chloride ions act as the hole catcher and move into the gas phase in the stable form of chlorine. Similar to heterogeneous structures, homogeneous systems not only enhance the hydrogen performance while ensuring the stability of metal‐oxo complexes, but also shorten the consumption of photogenerated carriers by dissolved impurities in the seawater. This new attempt of building pluralistic sub‐nanometric systems may offer novel design strategies with noble‐metal‐free catalysts and low‐cost candidates for traditional semiconductor materials in enhancing photocatalytic efficiency and performing chlorine evolution from seawater splitting.

Based on the tumor hypoxic microenvironment and the new programmed cell death mode of combined ferroptosis, an angelica polysaccharide-based nanocarrier material was synthesized. The polymer contains hydrophilic angelica polysaccharide (ASP) that is linked by azobenzene (AZO) linker with ferrocene (Fc), and then the side chain was covalently modified with arachidonic acid (AA). It was postulated that the polymer micelles could work as an instinctive liver targeting drug delivery carrier, owing to the existence of ASP with liver targeting. Moreover, the aim was to engineer hypoxia-responsive polymer micelles which was modified by AA, for selective enhancement of ferroptosis in solid tumor, via diminishing glutathione (GSH) under hypoxia. Finally, we synthesized the amphiphilic polymer micelles AA/ASP-AZO-Fc (AAAF) by self-assembling. The structure of AAAF was confirmed by 1H-NMR and FT-IR. Then, we exemplified the hydrophobic medication curcumin into polymer micelles AAAF@Cur, which has smooth and regular spheres. In vitro release test affirmed that AAAF@Cur can achieve hypoxia response to drug release. In addition, a series of cell experiments confirmed that hypoxia could enhance cell uptake and effectively improve the proliferation inhibitory activity of HepG2 cells. In conclusion, AAAF, as an effective cell carrier, is expected to develop in sensitizing ferroptosis and anti-tumor.

Abstract Rationale Genetic studies have proved the involvement of Tuberous sclerosis complex subunit 2 (Tsc2) in aortic aneurysm. However, the exact role of macrophage Tsc2 in the vascular system remains unclear. Here, we examined the potential function of macrophage Tsc2 in the development of aortic remodeling and aortic aneurysms. Methods and results Conditional gene knockout strategy combined with histology and whole-transcriptomic analysis showed that Tsc2 deficiency in macrophages aggravated the progression of aortic aneurysms along with an upregulation of proinflammatory cytokines and matrix metallopeptidase-9 in the angiotensin II-induced mouse model. G protein-coupled receptor 68 (Gpr68), a proton-sensing receptor for detecting the extracellular acidic pH, was identified as the most up-regulated gene in Tsc2 deficient macrophages compared with control macrophages. Additionally, Tsc2 deficient macrophages displayed higher glycolysis and glycolytic inhibitor 2-deoxy-D-glucose treatment partially attenuated the level of Gpr68. We further demonstrated an Tsc2-Gpr68-CREB network in macrophages that regulates the inflammatory response, proteolytic degradation and vascular homeostasis. Gpr68 inhibition largely abrogated the progression of aortic aneurysms caused by Tsc2 deficiency in macrophages. Conclusions The findings reveal that Tsc2 deficiency in macrophages contributes to aortic aneurysm formation, at least in part, by upregulating Gpr68 expression, which subsequently drives proinflammatory processes and matrix metallopeptidase activation. The data also provide a novel therapeutic strategy to limit the progression of the aneurysm resulting from Tsc2 mutations.

Mounting evidence indicates that histone modifications are involved in aging-associated cognitive decline (AACD) and can be transmitted to offspring over multiple generations under conditions of stress. Here, we investigated the effects of maternal sub-chronic inflammation caused by lipopolysaccharide (LPS) on AACD and histone modifications in the F1 and F2 generations of experimental mice as well as the potential sex specificity of intergenerational effects. In brief, F0-generation CD-1 dams were exposed to LPS (50 µg/kg) or saline (CON) during late pregnancy. Subsequently, F1 males and females (at 2 months-of-age) from the LPS treatment group were mated with non-littermates from the LPS group or wild-type mice to produce F2 generations of parental- (F2-LPS2), paternal- (F2M-LPS1) and maternal-origin (F2F-LPS1) mice. Then, CON-F1 males and females were mated with wild-type mice to generate F2 generations of paternal- (F2M-CON1) and maternal-origin (F2F-CON1). Next, we evaluated the cognitive ability and levels of hippocampal H4K12ac and H3K9me3 in the F1 and F2 offspring at 3- and 13 months-of-age. Overall, F1 male and female LPS groups presented with elevated corticosterone (P

Abstract Microneedling is a popular skin resurfacing and rejuvenation procedure. In order to develop better adjunct products for consumers, there is a scientific need to establish greater understanding of the mechanism in which microneedling stimulates regeneration within skin. The purpose of this study is to develop a physiologically relevant ex vivo tissue model which closely mimics the actual microneedling procedure to elucidate its mechanism of action. In this study, human ex vivo skin was subjected to microneedling treatment and cultured for 6 days. Histological analysis demonstrated that the ex vivo skin was able to heal from microneedling injury throughout the culture period. Microneedling treatment stimulated proliferation and barrier renewal of the skin. The procedure also increased the levels of inflammatory cytokines and angiogenic growth factors in a dynamic and time dependent fashion. The tissue demonstrated hallmark signs of epidermal regeneration through morphological and molecular changes after the treatment. This is one of the first works to date that utilizes microneedled ex vivo skin to demonstrate its regenerative behavior. Our model recapitulates the main features of the microneedling treatment and enables the evaluation of future cosmetic active ingredients used in conjunction with microneedling.

Appropriate physical activities and a biodiversity-rich environment are conducive to the relief of psychological stress, and pro-nature physical activities are a combination of the two, which has good application potential in antagonizing psychological stress, but the intervention mechanism is still unclear. The microbiota-gut-brain axis is cyclically associated with psychological stress, and psychological stress can affect the microbiota through the gut-brain pathway, and conversely, the microbiota can also affect the psychological stress-induced symptoms. It is suggested that the microbe-gut-brain axis may provide a new perspective and target for the treatment of psychological stress-related diseases. Pro-nature physical activity can improve the number of Firmicutes, short-chain fatty acids, Akkermansia bacteria, and the gut-brain barrier and further affect the HPA axis, BDNF, and serotonin pathways of gut-brain two-way communication, thereby maintaining the body’s homeostasis and reducing antagonistic psychological stress. According to the comprehensive influence of physical activities on the microbiota-gut-brain axis, a “green + exercise prescription hypothesis” in line with the holistic medical concept is revealed, which is expected to be effective in the prevention, alleviation, and treatment of irritable bowel syndrome and neurodegenerative diseases. It provides new means for treating psychological stress-related diseases such as mental disorders and mood disorders. In addition, it enlightens the construction of green infrastructure that is conducive to the diversified contact of microorganisms in outdoor physical activities venues and induces healthy interaction between the human body and the microbial population in the natural ecology. However, the current research is still in its early stages, and the intervention effect and mechanism of pro-nature physical activities need further demonstration in the future.

BackgroundThis study was aimed to examine the association between cigarette smoking in childhood and mortality in adulthood, and the impact of non-smoking duration among smokers who subsequently quit smoking.MethodsWe used data from 472,887 adults aged 18–85 years examined once in the US National Health Interview Survey in 1997–2014, which was linked to mortality data from the National Death Index up to 31 December 2015. Cigarette smoking status in childhood (age 6 to 17 years) and adulthood (age 18 to 85 years) was self-reported using a standard questionnaire at the time of participation in the survey. The vital status of participants due all-causes, cardiovascular disease (CVD), cancer and chronic lower respiratory diseases was obtained using mortality data from the National Death Index.ResultsDuring the mean follow-up of 8.75 years, compared with never smoking in childhood and adulthood, the risk of all-cause mortality among current adult smokers decreased slightly according to increasing age at smoking initiation: hazard ratios (HRs; 95% confidence intervals, CIs) were 2.54 (2.24–2.88) at age of 6–9 years, 2.44 (2.31–2.57) at age of 10–14 years, and 2.21 (2.12–2.31) at age of 15–17 years. Smoking cessation before the age of 30 years was not associated with increased risk of all-cause and cause-specific mortality (all p > 0.05) compared to never smoking.ConclusionMortality risk was higher in individuals who started smoking at an earlier age in childhood. Inversely, smoking cessation before the age of 30 years was not associated with an increased risk of mortality compared to never smoking.

Viral infection-induced cell death has long been considered as a double-edged sword in the inhibition or exacerbation of viral infections. Patients with severe Coronavirus Disease 2019 (COVID-19) are characterized by multiple organ dysfunction syndrome and cytokine storm, which may result from SARS-CoV-2-induced cell death. Previous studies have observed enhanced ROS level and signs of ferroptosis in SARS-CoV-2 infected cells or specimens of patients with COVID-19, but the exact mechanism is not clear yet. Here, we find SARS-CoV-2 ORF3a sensitizes cells to ferroptosis via Keap1-NRF2 axis. SARS-CoV-2 ORF3a promotes the degradation of NRF2 through recruiting Keap1, thereby attenuating cellular resistance to oxidative stress and facilitated cells to ferroptotic cell death. Our study uncovers that SARS-CoV-2 ORF3a functions as a positive regulator of ferroptosis, which might explain SARS-CoV-2-induced damage in multiple organs in COVID-19 patients and imply the potential of ferroptosis inhibition in COVID-19 treatment.

IntroductionCD155 is recently emerging as a promising target in malignancies. However, the relationship between CD155 expression and tumor microenvironment (TME) cell infiltration in gastric adenocarcinoma (GAC) has rarely been clarified.MethodsWe measured CD155 expression in specimens of gastric precancerous disease and GAC by immunohistochemistry. The association of CD155 expression with GAC progression and cells infiltration in TME was evaluated through 268 GAC tissues and public dataset analysis.ResultsWe showed that the expression of CD155 was positively correlated with the pathological development of gastric precancerous disease (r = 0.521, P < 0.0001). GAC patients with high CD155 expression had a poorer overall survival (P = 0.033). Moreover, CD155 expression correlated with aggressive clinicopathological features including tumor volume, tumor stage, lymph node involvement, and cell proliferation (P

Aging is a critical risk factor in idiopathic pulmonary fibrosis (IPF). Dysfunction and loss of type 2 alveolar epithelial cells (AEC2s) with failed regeneration is a seminal causal event in the pathogenesis of IPF, although the precise mechanisms for their regenerative failure and demise remain unclear. To systematically examine the genomic program changes of AEC2s in aging and after lung injury, we performed unbiased single-cell RNA-seq analyses of lung epithelial cells from uninjured or bleomycin-injured young and old mice, as well as from lungs of IPF patients and healthy donors. We identified three AEC2 subsets based on their gene signatures. Subset AEC2-1 mainly exist in uninjured lungs, while subsets AEC2-2 and AEC2-3 emerged in injured lungs and increased with aging. Functionally, AEC2 subsets are correlated with progenitor cell renewal. Aging enhanced the expression of the genes related to inflammation, stress responses, senescence, and apoptosis. Interestingly, lung injury increased aging-related gene expression in AEC2s even in young mice. The synergistic effects of aging and injury contributed to impaired AEC2 recovery in aged mouse lungs after injury. In addition, we also identified three subsets of AEC2s from human lungs that formed three similar subsets to mouse AEC2s. IPF AEC2s showed a similar genomic signature to AEC2 subsets from bleomycin-injured old mouse lungs. Taken together, we identified synergistic effects of aging and AEC2 injury in transcriptomic and functional analyses that promoted fibrosis. This study provides new insights into the interactions between aging and lung injury with interesting overlap with diseased IPF AEC2 cells.

Abstract Inverted perovskite solar cells (inverted‐PSCs) have exhibited advantages of longer stability, less hysteresis, and lower fabrication temperature when compared to their regular counterparts, which are important for industry commercialization. Because of the great efforts that have been conducted in the past several years, the obtained efficiency of inverted‐PSCs has almost caught up with that of the regular ones, 25.0% versus 25.7%. In this perspective, the recent studies on the design of high‐performance inverted‐PSCs based on diverse hole transport materials, as well as device fabrication and characterization are first reviewed. After that, the authors moved on to the interface and additive engineering that were exploited to suppress the nonradiative recombination. Finally, the challenges and possible research pathways for facilitating the industrialization of inverted‐PSCs were envisaged.

IntroductionErectile dysfunction (ED), especially psychological ED (pED), is usually accompanied with psychological factors, which are related to abnormal activity in brain regions involved in sexual behavior. However, the mechanisms underlying functional changes in the brain of pED are still unclear. The present study aimed to explore the abnormalities of brain function, as well as their relationships with sexual behavior and emotion in pED patients.Materials and methodsResting state functional magnetic resonance imaging (rs-fMRI) data were collected from 31 pED patients to 31 healthy controls (HCs). The values of amplitude of fractional amplitude of low-frequency fluctuation (fALFF) and functional connectivity (FC) were calculated and compared between groups. In addition, the associations between abnormal brain regions and clinical features were evaluated by Pearson correlation analyses.ResultsCompared to HCs, pED patients demonstrated decreased fALFF values in the left medial superior frontal gyrus (had decreased FC values with the left dorsolateral superior frontal gyrus), the left lingual gyrus (had decreased FC values with the left parahippocamal gyrus and insula), the left putamen (had decreased FC values with the right caudate) and the right putamen (had decreased FC values with the left putamen and the right caudate). The fALFF values of the left medial superior frontal gyrus were negatively correlated with the fifth item scores of International Index of Erectile Function (IIEF-5). Negative relationships were found between fALFF values of the left putamen and the second item scores of Arizona Sexual Scale (ASEX). FC values between the right putamen and caudate were negatively related to the state scores of State-Trait Anxiety Inventory (STAI-S).ConclusionAltered brain function were found in the medial superior frontal gyrus and caudate-putamen of pED patients, which were associated with sexual function and psychological condition. These findings provided new insights into the central pathological mechanisms of pED.

Abstract Mobility-control policy is a controversial nonpharmacological approach to pandemic control due to its restriction on people’s liberty and economic impacts. Due to the computational complexity of mobility control, it is challenging to assess or compare alternative policies. Here, we develop a pandemic policy assessment system that employs artificial intelligence (AI) to evaluate and analyze mobility-control policies. The system includes three components: (1) a general simulation framework that models different policies to comparable network-flow control problems; (2) a reinforcement-learning (RL) oracle to explore the upper-bound execution results of policies; and (3) comprehensive protocols for converting the RL results to policy-assessment measures, including execution complexity, effectiveness, cost and benefit, and risk. We applied the system to real-world metropolitan data and evaluated three popular policies: city lockdown, community quarantine, and route management. For each policy, we generated mobility-pandemic trade-off frontiers. The results manifest that the smartest policies, such as route management, have high execution complexity but limited additional gain from mobility retention. In contrast, a moderate-level intelligent policy such as community quarantine has acceptable execution complexity but can effectively suppress infections and largely mitigate mobility interventions. The frontiers also show one or two turning points, reflecting the safe threshold of mobility retention when considering policy-execution errors. In addition, we simulated different policy environments and found inspirations for the current policy debates on the zero-COVID policy, vaccination policy, and relaxing restrictions.

Abstract Background To evaluate the parameters derived from arterial spin labeling (ASL) and multi-b-value diffusion-weighted imaging (DWI) for differentiating retropharyngeal lymph nodes (RLNs) in patients with nasopharyngeal carcinoma (NPC). Methods This prospective study included 50 newly diagnosed NPC and 23 healthy control (HC) participants. RLNs of NPC were diagnosed according to the follow-up MRI after radiotherapy. Parameters derived from ASL and multi-b-value DWI, and RLNs axial size on pre-treatment MRI among groups were compared. Receiver operating characteristic curve (ROC) was used to analyze the diagnostic efficiency. Results A total of 133 RLNs were collected and divided into a metastatic group (n = 71) and two non-metastatic groups (n = 62, including 29 nodes from NPC and 33 nodes from HC). The axial size, blood flow (BF), and apparent diffusion coefficient (ADC) of RLNs were significantly different between the metastasis and the non-metastasis group. For NPC patients with a short axis < 5 mm or < 6 mm, or long axis < 7 mm, if BF > 54 mL/min/100 g or ADC ≤ 0.95 × 10−3 mm2/s, the RLNs were still considered metastatic. Compared with the index alone, a combination of size and functional parameters could improve the accuracy significantly, except the long axis combined with ADC; especially, combined size with BF exhibited better performance with an accuracy of 91.00–92.00%. Conclusions ASL and multi-b-value DWI could help determine the N stage of NPC, while the BF combination with RLNs size may significantly improve the diagnostic efficiency.

Genomic instability facilitates the evolution of cells, tissues, organs, and species. The progression of human malignancies can be regarded as the accumulation of genomic instability, which confers a high evolutionary potential for tumor cells to adapt to continuous changes in the tumor microenvironment. Nasopharyngeal carcinoma (NPC) is a head-and-neck squamous-cell carcinoma closely associated with Epstein–Barr virus (EBV) infection. NPC progression is driven by a combination of accumulated genomic instability and persistent EBV infection. Here, we present a review of the key characteristics of genomic instability in NPC and the profound implications of EBV infection. We further discuss the significance of profiling genomic instability for the assessment of disease progression and treatment efficacy, as well as the opportunities and challenges of targeted therapies for NPC based on its unique genomic instability.

Enterocytozoon bieneusi is a zoonotic pathogen with a wide range of animal host. There are only few reports of E. bieneusi infection in wild Chinese rhesus macaques. Here, we determined the prevalence of E. bieneusi in nine wild rhesus macaque populations and assessed their zoonotic potential by performed genotype of ITS gene. A total of 324 fecal samples of rhesus macaque were collected in nine geographical populations from five Chinese provinces (Sichuan, Chongqing, Qinghai, Tibet and Hainan). 38 samples (11.7%) were found to be infected with E. bieneusi, and 11 genotypes were identified including three known genotypes (D, EbpC and SCC-2) and eight novel genotypes named Mul6∼13. Genotype D (63.2%) was the most prevalent, being observed in seven populations except XZ-2 and QH, and other genotypes were identified only in a single area. According to the phylogenetic analysis, Mul6∼9, Mul11∼13 and zoonotic genotype D were clustered into Group 1, indicating that these genotypes may be potentially zoonotic. Among nine populations, population SC-3 had the highest infection rate (26.3%), and the lowest was the wild QH population without infection, but the difference of infection rate among the nine populations is not significant. It is concluded that, rhesus macaque populations are generally infected E. bieneusi in many areas of China, and there may be a risk of cross infection with E. bieneusi in some areas found having zoonotic genotypes, and these areas should be paid more attention to prevent.

Abstract Background This article is the first report of laparoscopic major hepatectomy of Hepatocellular carcinoma (HCC) following optimized portal vein embolization (oPVE). Case presentation The patient was diagnosed with a single 3 × 3.5 cm HCC located in segment 5 and 8 detected by enhanced computed tomography and magnetic resonance imaging. The lesion was adjacent to the right anterior and posterior portal veins, making it difficult to confirm the adequate liver functional remnant volume, surgical margin and R0 resection. In addition, the liver cirrhosis induced by a long history of chronic hepatitis B virus increased the potential risk of postoperative liver failure and refractory ascites. Therefore, we conducted a laparoscopic surgery following oPVE, by which the safe tumor margin was ensured and the outcome of the surgery was improved. The patient was discharged on the seventh day after the surgery. The AFP gradually decreased to a normal level during the 90-day follow-up. Conclusion This case report demonstrates that, in experienced hands for selected patients, laparoscopic hepatectomy after portal vein embolization is feasible and may be an alternative to open liver resection.

Brassica crops, which are of worldwide importance, provide various oil, vegetable and ornamental products, as well as feedstocks for animal husbandry and biofuel industry. Cinnamoyl-CoA reductase (CCR) is the entry point to the lignin pathway and a crucial locus in manipulation of associated traits, but CCR-associated metabolism and traits in Brassica crops have remained largely unstudied except in Arabidopsis thaliana. We report the identification of 16 CCR genes from Brassica napus and its parental species B. rapa and B. oleracea. The BnCCR1 and BnCCR2 subfamilies displayed divergent organ-specificity and participation in the yellow-seed trait. Their functions were dissected via overexpression of representative paralogs in B. napus. BnCCR1 was expressed preferentially in G- and H-lignin biosynthesis and vascular development, while BnCCR2 was expressed in S-lignin biosynthesis and interfascicular fiber development. BnCCR1 showed stronger effects on lignification-related development, lodging resistance, phenylpropanoid flux control, and seed coat pigmentation, whereas BnCCR2 showed a stronger effect on sinapate biosynthesis. BnCCR1 upregulation delayed bolting and flowering time, while BnCCR2 upregulation weakened the leaf vascular system in consequence of suppressed G-lignin accumulation. BnCCR1 and BnCCR2 were closely but almost oppositely linked with glucosinolate metabolism via inter-pathway crosstalk. We conclude that BnCCR1 and BnCCR2 subfamilies offer great but differing potential for manipulating traits associated with phenylpropanoids and glucosinolates. This study reveals the CCR1–CCR2 divergence in Brassicaceae and offers a resource for rapeseed breeding for lodging resistance, yellow-seed traits, and glucosinolate traits.

The amount of cellular communication network traffic has increased dramatically in recent years, and this increase has led to a demand for enhanced network performance. Communication load balancing aims to balance the load across available network resources and thus improve the quality of service for network users. Most existing load balancing algorithms are manually designed and tuned rule-based methods where near-optimality is almost impossible to achieve. Furthermore, rule-based methods are difficult to adapt to quickly changing traffic patterns in real-world environments. Reinforcement learning (RL) algorithms, especially deep reinforcement learning algorithms, have achieved impressive successes in many application domains and offer the potential of good adaptabiity to dynamic changes in network load patterns. This survey presents a systematic overview of RL-based communication load-balancing methods and discusses related challenges and opportunities. We first provide an introduction to the load balancing problem and to RL from fundamental concepts to advanced models. Then, we review RL approaches that address emerging communication load balancing issues important to next generation networks, including 5G and beyond. Finally, we highlight important challenges, open issues, and future research directions for applying RL for communication load balancing.

SARS-CoV Spike (S) protein shares considerable homology with SARS-CoV-2 S, especially in the conserved S2 subunit (S2). S protein mediates coronavirus receptor binding and membrane fusion, and the latter activity can greatly influence coronavirus infection. We observed that SARS-CoV S is less effective in inducing membrane fusion compared with SARS-CoV-2 S. We identify that S813T mutation is sufficient in S2 interfering with the cleavage of SARS-CoV-2 S by TMPRSS2, reducing spike fusogenicity and pseudoparticle entry. Conversely, the mutation of T813S in SARS-CoV S increased fusion ability and viral replication. Our data suggested that residue 813 in the S was critical for the proteolytic activation, and the change from threonine to serine at 813 position might be an evolutionary feature adopted by SARS-2-related viruses. This finding deepened the understanding of Spike fusogenicity and could provide a new perspective for exploring Sarbecovirus' evolution.

In the neuroendocrine system, corticotropin-releasing hormone (CRH) plays an important role in the hypothalamic–pituitary–adrenal/interrenal (HPA/HPI) axis. It exerts its effects by activating CRHRs, which belong to the class B G protein-coupled receptor family. Two characteristic genes of CRHR1 subtypes in the Larimichthys crocea genome were identified: LcCRHR1-1 and LcCRHR1-2. Alignments indicated that they were highly homologous to known and validated teleost CRHR1s. The CDS sequences of the two receptors were cloned into the pEGFP-N1 plasmid, and membrane localization of the fusion expressing LcCRHR1-1-EGFP and LcCRHR1-2-EGFP was revealed in HEK293 cells. Treatment with LcCRH could lead to two receptors internalization and trigger a significant increase in the secondary messenger cAMP and Ca2+ and mitogen-activated protein kinase phosphorylation in an LcCRH dose-dependent manner. Based on quantitative real-time PCR, LcCRHR1s were expressed in all examined tissues and highly expressed in the brain and ovaries. Furthermore, immunohistochemical findings showed the specific localization of CRHR1s in ovarian follicle cells. Collectively, our study identified two CRH receptors in L. crocea and suggested that the CRH/CRHR1 system is potentially involved in the neuroendocrine regulation of reproduction in this marine fish.

The endoplasmic reticulum (ER) is an important cellular organelle, and ER dysfunction has an important impact on a variety of biological processes. In this study, we explored the role of ER stress in cervical cancer by establishing a prognostic model related to ER stress. This study included 309 samples from the TCGA database and 15 pairs of RNA sequencing data before and after radiotherapy. ER stress characteristics were obtained by the LASSO regression model. The prognostic value of risk characteristics was analyzed by Cox regression, Kaplan‒Meier, and ROC curves. The effects of radiation and radiation mucositis on ER stress were evaluated. We found that ER stress-related genes were differentially expressed in cervical cancer and could predict its prognosis. The LASSO regression model suggested that risk genes had a strong ability to predict prognosis. In addition, the regression suggests that the low-risk group may benefit from immunotherapy. Cox regression analysis showed that FOXRED2 and N staging could be independent factors affecting prognosis. ERN1 was significantly affected by radiation and may be related to the occurrence of radiation mucositis. In conclusion, ER stress activation might have a high value in the treatment and prognosis of cervical cancer and has good clinical prospects.

Ridgetail white prawn, Exopalaemon carinicauda, with high reproductive capacity can reproduce up to three or four generations a year. In exploring the genetic factors affecting the gonadal development of E. carinicauda, we cloned and studied the function of the ubiquitin-like, containing PHD and RING finger domains 1 (uhrf1) gene. The open reading frame of uhrf1 gene was 2286 bp, encoding a total of 761 amino acids. The Uhrf1 has UBL, TTD, PhD, SRA, and ring finger domains that are associated with genome methylation, histone recognition and chromatin modification. According to the phylogenetic analysis, the amino acid sequence of Ec-uhrf1 has the highest similarity with Litopenaeus vannamei uhrf1, and it is a branch of Penaeus monodon and L. vannamei. The real-time quantitative PCR showed that the expression level of uhrf1 was highest in ridgetail white prawn ovarian tissue, which was significantly higher than that of other tissues (P

IntroductionNurses have a high prevalence of occupational low back pain, especially since the outbreak of the COVID-19 pandemic, which has increased the nurses' workloads. It has brought a huge burden on nurses and their professional development. Nurses' occupational low back pain prevention capacity is the logical starting point and core of interventions to prevent its occurrence. To date, there is no study investigating it with a scientific scale. Therefore, a multicenter cross-sectional study was conducted to explore the current status of nurses' capacity in occupational low back pain prevention and its influencing factors in China.MethodsUsing a two-stage, purposive and convenience mixed sampling method, 1331 nurses from 8 hospitals across 5 provinces (Hubei, Zhejiang, Shandong, Henan, and Sichuan) in the southern, western, northern, and central areas of mainland China were involved in this study. The demographic questionnaire and occupational low back pain prevention behavior questionnaire were used for data collection. The descriptive analysis, univariate analysis, and multiple stepwise linear regression were used for data analysis.ResultsThe results showed that the occupational low back pain prevention behavior questionnaire score was 89.00 (80.00, 103.00) [M (Q1, Q3)], which indicated that nurses' ability was at a moderate level. Participation in prevention training before, perceived stress at work, and working hours per week were predictors for nurses' occupational low back pain prevention capacity.DiscussionTo improve nurses' prevention ability, nursing managers should organize various training programs, strengthen regulations to reduce nurses' workload and stress, provide a healthy workplace, and offer incentives to motivate nurses.