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Due to the rapid changes in burial depth in steeply inclined reservoirs (SICR), there is a significant change in stress in the up-dip and down-dip directions within the drainage range of CBM wells, and the expansion of fracturing fractures is different from that of near horizontal reservoirs. Based on the field fracturing data of steeply inclined reservoirs in Fukang West Block of southern Junggar Basin, this study analyzed the bottom hole pressure and fracture morphology characteristics in the process of hydraulic fracture of steeply inclined reservoirs, studied the fracture propagation characteristics of steeply inclined reservoirs by using the finite element numerical method, and expounded the impact of dip angle (stress gradient) on the fracture propagation of coal reservoirs. The results show that according to the stress and fracture propagation characteristics in the up-dip and down-dip dip directions, steeply dipping reservoirs are divided into shallow-steeply dipping reservoirs, middle-steeply dipping reservoirs, and deep-steeply dipping reservoirs. The hydraulic fracture propagation of shallow-steeply inclined reservoirs (with vertical stress less than horizontal stress) can be divided into three stages: fracture propagation in the up-dip direction, fracture stopping propagation, and fracture propagation in the down-dip direction; the fractures in the middle-steeply inclined reservoirs (with the vertical stress in the up-dip direction is less than the horizontal stress, and the vertical stress in the down-dip direction is greater than the horizontal stress) first expand in the up-dip direction, and then the fractures begin to turn perpendicular to the dip direction along the boundary of the up-dip direction and where the vertical stress is greater than the horizontal stress; deep-steeply inclined reservoirs (with vertical stress greater than horizontal stress) fractures propagate perpendicular to the dip direction. As the dip angle of the reservoir increases, the propagation rate of shallow reservoirs increases in the up-dip direction, while the rate decreases in the down-dip direction; the fractures in the middle-steeply inclined reservoirs gradually propagated from along the dip direction to perpendicular to the direction. The difference in fracture propagation in up-dip and down-dip direction of steeply inclined reservoirs is mainly due to the difference in fracture pressure caused by stress changes at different burial depths, causing the fractures to first propagate along the dominant channel with low stress.

Abstract Internal phosphorus loading (IPL), as an important part of lake phosphorus cycle and the key to solve the eutrophication problem, is still an important cause of regional and seasonal algal blooms for some mesotrophic lakes located in plateau areas. We investigated the composition, distribution of P fractions in sediments and suspended particulate matter (SPM) of Erhai Lake, southwest China, and explored the relationships between environmental variables and spatial-temporal variations of P fractions. The total P (TP) in surface sediments ranged from 817 to 1216 mg/kg, with inert Ca-P (32%) and Res-P (24%) predominating, at a moderate level. The comparison of short-term release fluxes (0.08 mg/(m2·d)) and long-term release fluxes (0.09 mg/(m2·d)) reflected that the northern region was recovering slowly from the previous P pollution. Mobile-P (the sum of loosely adsorbed P, iron bound P, and organic P) accounted for 52.3% of the TP in SPM and showed high spatial-temporal variations, which were closely related to the growth of algae throughout the investigation. The results suggested that sediments could make a sustained contribution to IPL, and that the P in SPM was highly active and significantly contributed to eutrophication in Erhai Lake especially at the time of seasonal alternations. Our data provided important theoretical bases for the relationship between internal phosphorus loading and eutrophication in plateau lakes.

Abstract The decrease in sperm count and infertility is a global issue that remains unresolved. By screening environmental bacterial isolates, we have found that a novel lactic acid bacterium, Lactiplantibacillus plantarum SNI3, increased testis size, testosterone levels, sperm count, sexual activity and fertility in mice that have consumed the bacteria for four weeks. The abundance of L. plantarum in the colon microbiome was positively associated with sperm count. Fecal microbiota transplantation (FMT) from L. plantarum SNI3-dosed mice improved testicular functions in microbiome-attenuated recipient animals. To identify mediators that confer pro-reproductive effects on the host, untargeted in situ mass spectrometry metabolomics was performed on testis samples of L. plantarum SNI3-treated and control mice. Enrichment pathway analysis revealed several perturbed metabolic pathways in the testis of treated mice. Within the testis, a dipeptide, glutamyl-glutamate (GluGlu) was the most upregulated metabolite following L. plantarum SNI3 administration. To validate the pro-reproductive feature of GluGlu, systemic and local injections of the dipeptide have been performed. γ-GluGlu increased sperm count but had no effect on testosterone. These findings highlight the role of γ-GluGlu in mediating spermatogenetic effects of L. plantarum on the male mouse host and –following relevant human clinical trials- may provide future tools for treating certain forms of male infertility.

Abstract Background Camellia nitidissima is a rare, prized camellia species with golden-yellow flowers. It has a high ornamental, medicinal, and economic value. Previous studies have shown substantial flavonol accumulation in C. nitidissima petals during flower formation. However, the mechanisms underlying the golden flower formation in C. nitidissima remain largely unknown. Results We performed an integrative analysis of the transcriptome, proteome, and metabolome of the petals at five flower developmental stages to construct the regulatory network underlying golden flower formation in C. nitidissima. Metabolome analysis revealed the presence of 323 flavonoids, and two flavonols, quercetin glycosides and kaempferol glycosides, were highly accumulated in the golden petals. Transcriptome and proteome sequencing suggested that the flavonol biosynthesis-related genes and proteins upregulated and the anthocyanin and proanthocyanidin biosynthesis-related genes and proteins downregulated in the golden petal stage. Further investigation revealed the involvement of MYBs and bHLHs in flavonoid biosynthesis. Expression analysis showed that flavonol synthase 2 (CnFLS2) was highly expressed in the petals, and its expression positively correlated with flavonol content at all flower developmental stages. Transient overexpression of CnFLS2 in the petals increased flavonol content. Furthermore, correlation analysis showed that the jasmonate (JA) pathways positively correlated with flavonol biosynthesis, and exogenous methyl jasmonate (MeJA) treatment promoted CnFLS2 expression and flavonol accumulation. Conclusions Our findings showed that the JA-CnFLS2 module regulates flavonol biosynthesis during golden petal formation in C. nitidissima.

Abstract Ultra-low-power consumption and high-speed integrated switches are highly desirable for future data centers and high-performance optical computers. In this study, we proposed an ultra-low-power consumption silicon electro-optic switch based on photonic crystal nanobeam cavities on a foundry platform. The proposed switch showed an ultra-low static-tuning power of 0.10 mW and a calculated dynamic switching power of 6.34 fJ/bit, with a compact footprint of 18 μm × 200 μm. Additionally, a 136-Gb/s four-level pulse amplitude modulation signal transmission experiment was carried out to verify the capability of the proposed electro-optic switch to support high-speed data transmission. The proposed device has the lowest static-tuning power consumption among silicon electro-optic switches and the highest data transmission rate. The results demonstrate the potential applications of this switch in high-performance optical computers, data center interconnects, optical neural networks, and programmable photonic circuits.

Abstract This study aimed to develop a physiologically based pharmacokinetic/pharmacodynamic model (PBPK/PD) of meropenem for critically ill patients. A PBPK model of meropenem in healthy adults was established using PK-Sim software and subsequently extrapolated to critically ill patients based on anatomic and physiological parameters. The mean fold error (MFE) and geometric mean fold error (GMFE) methods were used to compare the differences between predicted and observed values of pharmacokinetic parameters Cmax, AUC0-∞, and CL to evaluate the accuracy of the PBPK model. The model was verified using meropenem plasma samples obtained from Intensive Care Unit (ICU) patients, which were determined by HPLC-MS/MS. After that, the PBPK model was combined with a PKPD model, which was developed based on f%T > MIC. Monte Carlo simulation was utilized to calculate the probability of target attainment (PTA) in patients. The developed PBPK model successfully predicted the meropenem disposition in critically ill patients, wherein the MFE average and GMFE of all predicted PK parameters were within the 1.25-fold error range. The therapeutic drug monitoring (TDM) of meropenem was conducted with 92 blood samples from 31 ICU patients, of which 71 (77.17%) blood samples were consistent with the simulated value. The TDM results showed that meropenem PBPK modeling is well simulated in critically ill patients. Monte Carlo simulations showed that extended infusion and frequent administration were necessary to achieve curative effect for critically ill patients, whereas excessive infusion time (> 4 h) was unnecessary. The PBPK/PD modeling incorporating literature and prospective study data can predict meropenem pharmacokinetics in critically ill patients correctly. Our study provides a reference for dose adjustment in critically ill patients.

Gymnocypris eckloni, an economically important cold-water fish widely cultivated in southwest China, is at increased risk of prolonged exposure to heat stress owing to persistent high temperatures in summer, extreme climate changes, and expansion of factory farming. In this study, G. eckloni was subjected to both chronic and acute heat stress, with subsequent analysis focusing on changes in the pathological and physiological characteristics and transcriptomic and metabolic responses of the liver to high temperature. The results revealed heat stress-induced damage to liver tissues, lipid accumulation and mitochondrial abnormalities in hepatocytes, and an increased number of apoptotic cells, with the damage being more severe under acute heat stress conditions. Assessment of biochemical indices showed that the antioxidant enzyme catalase (CAT) was activated in response to oxidative stress and energy demands increased following heat stress. Transcriptomic analysis showed significant enrichment in the protein processing in the endoplasmic reticulum pathway, along with upregulation of key genes associated with protein degradation (hsp40, hsp70, hsp90, ero1l, and pdia4) and activation of the unfolded protein response (UPR), which effectively reduces or clears the accumulation of misfolded proteins to combat stress. Most identified differential metabolites were associated with amino acid and lipid metabolism under heat stress. Notably, integrated transcriptomic and metabolomic analysis suggested that tryptophan metabolism played an important role in the adaptation of G. eckloni to chronic heat stress. These findings improve the understanding of the mechanisms through which G. eckloni adapts to high temperatures, providing a valuable foundation and novel avenues for developing strategies to alleviate the effects of heat stress and improve the outcomes of aquaculture.

Lanthanum-modified-bentonite(LMB) has been applied for eutrophication management as a phosphate(P)-binding agent in many lakes. However, re-eutrophication took place several years or decades later after the first practice of capping due to dynamic environmental factors in the plateau lake. Here, we investigated the effect of long-term capping and integrated environmental factors in the plateau lake including alkalinity, organic matter, disturbance and photodegradation to the LMB immobilization. Long-term LMB immobilization exhibited C accumulation(82.3%), La depletion(53.5%) and lager size effect in the sediment particle, indicating the breakage of La-O-P bonds and the formation of La-O-C bonds over immobilization time. Additionally, pH(8–10) in the plateau lake could enhance the P desorption and decrease P adsorption through electrostatic repulsion enhancement with the zeta potential reduction(7.2 mV). Further disturbance experiment indicated a significant releasing trend of active P and DGT-labile P from the solid phase, pore water to the overlying water after disturbances due to resuspended releasing, particle size and amorphous Fe, Mn and Al's redistribution. Moreover, 31P NMR and EPR results indicated photodegradation after disturbance converted diester phosphate into orthophosphate with long-term LMB immobilization via the oxidation of ·OH in the sediment of the plateau lake. Therefore, management issues for Xingyun Lake may apply to other plateau lakes with low external P input, intermediate depth and intense disturbance.

Metasurfaces have shown unique application value in the field of holography due to its outstanding ability to manipulate electromagnetic waves. However, improving the design efficiency and imaging quality remains a challenging task. In this work, we propose a deep learning method that can design holographic metasurface structures on demand, with the Mean Absolute Error (MAE) of 0.04 for both amplitude and phase. We utilize this method to inverse design all-silicon-based metasurfaces operating in the terahertz range, achieving a MAE of 0.015 for two target images. This method not only significantly enhances the design efficiency of holographic metasurfaces but also enables continuous modulation of both phase and amplitude. Consequently, it greatly improves both the design efficiency and imaging quality of holographic metasurfaces, providing a new direction for their design.

Objective To assess the factors that affect the capacity of community pharmacists to deliver pharmacy services (PSs) in Zhengzhou, China.Design An online, cross-sectional survey was conducted.Setting and participants A stratified sampling method was used to select community pharmacists for questionnaires. A total of 124 community pharmacists from various districts of Zhengzhou were included in this study.Results Principal component regression analysis showed that cumulative hours of continuing education (CE), job satisfaction, career prospects, awareness of the need for CE and income had a positive impact on pharmacists’ capacity to deliver PS, with a gradually decreasing degree of influence.Conclusions Most pharmacists felt that their capacity to provide PS met the basic public requirements. Cumulative CE hours had the most significant effect on pharmacists’ capacity to provide PS, while income had the least effect. The government, grassroots community pharmacies, pharmacists and the public should formulate timely and targeted measures to enhance the PS capacity of community pharmacists.

Abstract Myocardial infarction accompanied by diabetes mellitus is accepted as the most serious type of coronary heart disease, and among the current treatment strategies, the precise delivery of protective drugs for inhibiting cardiomyocyte apoptosis is still a challenge. In this study, we developed a biodegradable nanoparticles‐based delivery system with excellent macrophage escape, cardiac targeting, and drug release properties to achieve targeted therapy of myocardial infarction. Specifically, a copolymer of p(DMA–MPC–CD) combining self‐adhesion, hydration lubrication, and targeting peptide binding site was successfully prepared by free radical copolymerization, and it was self‐assembled on the surface of melatonin‐loaded dendritic mesoporous silica nanoparticles (bMSNs) following the integration of adamantane‐modified cardiac homing peptide (CHP) based on supramolecular host–guest interaction. Importantly, a hydration layer formed around the zwitterionic phosphorylcholine groups of the multifunctional nanoparticles, which was confirmed by the enhancement in hydration lubrication and reduction in coefficient of friction, prevented the nanoparticles from phagocytosis by the macrophages. The in vivo bioluminescence imaging test indicated that the nanoparticles were endowed with satisfied cardiac targeting capability, and the in vivo mice study demonstrated that the intravenous injection of drug‐loaded nanoparticles (namely bMSNs–Mel@PDMC–CHP) effectively reduced cardiomyocyte apoptosis, alleviated myocardial interstitial fibrosis, and enhanced cardiac function.

BackgroundThe present study aimed to analyze the independent risk factors for intraoperative bleeding in Siewert II adenocarcinoma of the esophagogastric junction (AEG) using two minimally invasive surgical approaches, namely, the laparoscopy-assisted abdominal trans-hiatal (LTH) method and transthoracic-laparoscopic esophagectomy (TLE).MethodsThe clinical data of 100 patients with SiewertII AEG admitted to our hospital from October 2017 to October 2020 were retrospectively analyzed. According to the type of surgery, the patients were divided into LTH approach group and TLE approach group. The differences between the clinical characteristics of the patients in different groups and the differences in the intraoperative bleeding and prognosis between different surgical procedures were analyzed and compared using the t-test and chi-squared test. Multiple linear regression was used to identify the independent risk factors affecting the amount of intraoperative bleeding in patients.ResultsThe results of this study showed that patients in the LTH group had significantly less intraoperative bleeding and operative time and significantly better postoperative recovery than the TLE group. The results of multivariate linear regression showed that the combined trans-thoracic-abdominal approach (P=0.000), advanced age (P=0.014), larger BMI (P=0.000), and larger tumor diameter (P=0.001) were the independent risk factors influencing the increase in intraoperative bleeding.ConclusionIn addition to the conventional factors that affect intraoperative bleeding, such as the patient’s general condition, operation time, and tumor size, LTH surgery is another way to avoid intraoperative bleeding for Siewert type II AEG patients and can significantly improve postoperative recovery.

BackgroundIntramuscular hemangioma is a vascular malformation occurring in muscle tissues. It is most common in skeletal muscles of limbs, especially lower limbs in childhood. The intercostal intramuscular hemangioma with sternal invasion is very rare.Case presentationThe 47-year-old female patient was hospitalized due to “suddenly chest pain for 4 days”. Chest contrast-enhanced CT indicated bony changes in the sternum, accompanied by soft tissue shadows in the posterior sternum and diaphragmatic angle. After admission, physical examination showed: peristernal tenderness, percussion pain, other no obvious positive signs. PET-CT examination indicated that there was a high possibility of benign sternal changes. No cancer cells were found by sternal puncture. Surgical biopsy was performed and pathological findings were consistent with intramuscular hemangioma.ConclusionIntramuscular hemangioma with bone invasion is very rare, imaging examination is difficult to indicate obvious evidence, preoperative diagnosis is difficult, complete surgical resection is very important, more personalized treatment should be provided according to the overall situation of the patient.

Aim: The present work explored the mechanism of dimethyl phthalate (DMP, the environmental contaminant) exposure in inducing cognitive impairment. Methods: Targets and regulatory networks related to DMP-brain injury-cognitive impairment were analyzed through network pharmacology. DMP exposure was carried out to simulate DMP environmental uptake, whereas Morris water maze was performed for examining cognitive impairment. Additionally, inflammatory cytokine levels within tissues were measured. hematoxylin-eosin staining(H&E) and Nissl staining was conducted to examine brain tissue injury, while Western blot was carried out for identifying protein levels. After applying.Small interfering RNA(siRNA-COX2) and celecoxib-COX2 inhibitors separately, we analyzed impacts of DMP. Besides, in vitro experiments were performed to analyze impacts of DMP on microglial activation. Results: As suggested by network pharmacology,Cyclooxygenase-2-PTGS2 (COX2) showed significant relation to DMP, and it exerted its effect via COX2. Following DMP exposure, mice experienced obvious cognitive impairment and brain damage, besides, microglial cells were activated, and inflammatory cytokines were up-regulated. Applying siRNA-COX2 and celecoxib-COX2 suppressed DMP’s impact and mitigated mouse cognitive impairment. Based on in vitro analysis, DMP led to microglial activation and neuroinflammation. Conclusion: DMP exposure causes neuroinflammation via the COX2-regulated microglial activation, thus leading to cognitive impairment. COX2 may serve as the key action target of DMP.

Abstract Objective Nowadays, there has been limited Mendelian randomization (MR) research focusing on the causal relationship between estradiol and vaginitis. Therefore, this study conducted a two-way MR study to clarify the causal effect and related influencing factors between them. Methods All genetic datasets were obtained using publicly available summary statistics based on individuals of European ancestry from the IEU GWAS database. MR analysis was performed using MR-Egger, weighted median (WM) and inverse variance weighted (IVW) methods to assess the causal relationship between exposure and outcome and to validate the findings by comprehensively evaluating the effects of pleiotropic effects and outliers. Results MR analysis revealed no significant causal relationship between estradiol and vaginitis risk. There was a negative correlation between estradiol and age at menarche (IVW, OR: 0.9996, 95% CI: 0.9992–1.0000, P = 0.0295; WM, OR: 0.9995, 95% CI: 0.9993–0.9998, P = 0.0003), and there was a positive correlation between age at menarche and vaginitis (IVW, OR: 1.5108, 95% CI: 1.1474–2.0930, P = 0.0043; MR-Egger, OR: 2.5575, 95% CI: 1.7664–9.6580, P = 0.0013). Estradiol was negatively correlated with age at menopause (IVW, OR: 0.9872, 95% CI: 0.9786–0.9959, P = 0.0041). However, there was no causal relationship between age at menopause and vaginitis (P > 0.05). In addition, HPV E7 Type 16, HPV E7 Type 18, and Lactobacillus had no direct causal effects on estradiol and vaginitis (P > 0.05). Sensitivity analyses revealed no heterogeneity and horizontal pleiotropy. Conclusion When estrogen levels drop, it will lead to a later age of menarche, and a later age of menarche may increase the risk of vaginitis, highlighting that the longer the female reproductive tract receives estrogen stimulation, the stronger the defense ability is formed, and the prevalence of vaginitis is reduced. In conclusion, this study indirectly supports an association between reduced level of estrogen or short time of estrogen stimulation and increased risk of vaginitis.

Abstract Background Parkinson’s disease (PD) is a progressive neurodegenerative disease that usually happens to elderly people, with a wide range of motor and dementia symptoms. An objective and convenient biomarker for PD detection is extremely valuable, especially one that could be acquired non-invasively and low-costly. To this end, this study used resting-state scalp electroencephalography (EEG) signals to explore dynamic functional-connectivity (dFC) states between each pair of EEG recording channels, without source localization. Methods dFC refers to synchronization patterns over time between each pair of EEG channels. First, five frequency bands were extracted from EEG signals with fourth-order Butterworth bandpass filter, including delta (0.5–4 Hz), theta (4–8 Hz), alpha (8–13 Hz), beta (8–30 Hz) and gamma (30–50 Hz). Then, after non-random joint fluctuation was measured with weighted symbolic mutual information (wSMI) algorithm, whole-brain dynamic channelwise dFC states were estimated, and classified with k-means clustering. At last, FC state occurrences were calculated, and ANOVA analyses were performed for each state. Two open-source resting-state EEG data sets ( https://doi.org/10.18112/openneuro.ds002778.v1.0.4 : 32 channels, 16 health controls and 15 PD subjects. https://doi.org/10.18112/openneuro.ds003490.v1.1.0 : 64 channels, 25 health controls and 25 PD subjects) were used to test our methods. Results Significant changes in proportions of various dFC states within beta frequency-band were consistently observed in these both data sets (p value

Mixed matrix membranes (MMMs) could combine the advantages of both polymeric membranes and porous fillers, making them an effective alternative to conventional polymer membranes. However, interfacial incompatibility issues, such as the presence of interfacial voids, hardening of polymer chains, and blockage of micropores by polymers between common MMMs fillers and the polymer matrix, currently limit the gas separation performance of MMMs. Ternary phase MMMs (consisting of a filler, an additive, and a matrix) made by adding a third compound, usually functionalized additives, can overcome the structural problems of binary phase MMMs and positively impact membrane separation performance. This review introduces the structure and fabrication processes for ternary MMMs, categorizes various nanofillers and the third component, and summarizes and analyzes in detail the CO2 separation performance of newly developed ternary MMMs based on both rubbery and glassy polymers. Based on this separation data, the challenges of ternary MMMs are also discussed. Finally, future directions for ternary MMMs are proposed.

Abstract Aims This study sought to assess the effect of treatment of sacubitril/valsartan (S/V) on improving cardiac function and reversing cardiac remodelling in patients with acute coronary syndrome (ACS) complicated with heart failure with reduced ejection fraction after percutaneous coronary intervention (PCI). Methods and results We enrolled 275 ACS patients with reduced left ventricular ejection fraction after PCI. The patients were divided into the routine and S/V groups according to the treatment drugs. The symptoms, N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) concentrations, echocardiographic parameters [left ventricular ejection fraction (LVEF), left ventricular mass index (LVMI), left ventricular end‐diastolic volume index (LVEDVI), and left ventricular end‐systolic volume index (LVESVI)], major adverse cardiac events (MACEs), and adverse reactions were recorded at baseline and 6 months after treatment when a clinical follow‐up was performed. The S/V group was further divided into prespecified subgroups including unstable angina (UA) group, non‐ST‐elevation myocardial infarction (NSTEMI) group, and ST‐elevation myocardial infarction (STEMI) group according to the type of ACS. We analysed the changes in LVEF, LVMI, LVEDVI, LVESVI, and NT‐proBNP in both groups and evaluated the correlation between the changes in the above variables (ΔLVEF, ΔLVMI, ΔLVEDVI, ΔLVESVI, and ΔNT‐proBNP). Cox regression model was used to assess the independent risk factors of MACE. Prespecified subgroup analyses were also conducted. Compared with baseline, LVEF increased significantly (P

AIM: We investigated the mechanism by which the environmental toxin acrylamide (AM) promotes depression. Methods: A depression mouse model was constructed using the chronic unpredictable mild stress method, AM was administered orally to simulate the exposure state. Depressive-like behavioral changes were assessed by open field test, elevated plus maze test, swimming test, and sucrose preference test. Enzyme-linked immunosorbent assay (ELISA) was used to detect tissue inflammatory factor levels, hematoxylin and eosin (H&E) and Nissl staining to detect neuronal damage, immunohistochemical staining to detect IBA-1 expression, and Western-blotting to detect protein levels. GSDMD knockout (KO) mice and the GSDMD inhibitor LDC7559 were used to inhibit GSDMD. In vitro, primary microglia were used, and AM intervention was applied to detect the levels of cellular inflammatory factors, and fluorescence staining was used to detect GSDMD-NT, and propidium iodide (PI) was used to detect the level of pyroptosis. Results: AM can exacerbate CUMS-like depression in mice, increase the levels of inflammatory factors in brain tissue, and worsen neuronal damage, with upregulation of IBA-1 expression, and can increase the expression of NLRP3, GSDMD, and GSDMD-NT. When GSDMD-KO or LDC7559 intervention was applied, it could antagonize the effects of AM and improve CUMS-like depression. In microglial cell experiments, AM could promote pyroptosis in microglial cells, increase the expression of inflammatory factors, and when GSDMD-KO was applied, it could inhibit the effects of AM. Conclusion: AM can promote the progression of depression in CUMS-like mice via GSDMD-mediated pyroptosis, while also increasing tissue inflammatory levels. GSDMD is an important target for the neurotoxicity of AM.

Based on the complexity and metrological requirements of temperature calibration within the rotor of a medical low-temperature centrifuge, a wireless temperature calibration device for medical centrifuges has been designed and developed. The temperature probe is integrated into the centrifuge tube, and the entire device can be placed inside the rotor of the centrifuge, allowing for the measurement and analysis of the actual temperature of the test solution inside the centrifuge tube under dynamic rotation conditions. Furthermore, the force situation during dynamic calibration is analyzed and performance tested. The calibration device can consistently and dependably achieve dynamic temperature data acquisition under high-speed conditions of medical low-temperature centrifuges, facilitating dynamic temperature calibration within the centrifuge rotor and offering support for centrifuge temperature control processes.

We review the integration techniques for incorporating various materials into silicon-based devices. We discuss on-chip light sources with gain materials, linear electro-optic modulators using electro-optic materials, low-power piezoelectric tuning devices with piezoelectric materials, highly absorbing materials for on-chip photodetectors, and ultra-low-loss optical waveguides. Methodologies for integrating these materials with silicon are reviewed, alongside the technical challenges and evolving trends in silicon hybrid and heterogeneously integrated devices. In addition, potential research directions are proposed. With the advancement of integration processes for thin-film materials, significant breakthroughs are anticipated, leading to the realization of optoelectronic monolithic integration featuring on-chip lasers.

Introduction Missed fractures are the most frequent diagnostic error attributed to clinicians in UK emergency departments and a significant cause of patient morbidity. Recently, advances in computer vision have led to artificial intelligence (AI)-enhanced model developments, which can support clinicians in the detection of fractures. Previous research has shown these models to have promising effects on diagnostic performance, but their impact on the diagnostic accuracy of clinicians in the National Health Service (NHS) setting has not yet been fully evaluated.Methods and analysis A dataset of 500 plain radiographs derived from Oxford University Hospitals (OUH) NHS Foundation Trust will be collated to include all bones except the skull, facial bones and cervical spine. The dataset will be split evenly between radiographs showing one or more fractures and those without. The reference ground truth for each image will be established through independent review by two senior musculoskeletal radiologists. A third senior radiologist will resolve disagreements between two primary radiologists. The dataset will be analysed by a commercially available AI tool, BoneView (Gleamer, Paris, France), and its accuracy for detecting fractures will be determined with reference to the ground truth diagnosis. We will undertake a multiple case multiple reader study in which clinicians interpret all images without AI support, then repeat the process with access to AI algorithm output following a 4-week washout. 18 clinicians will be recruited as readers from four hospitals in England, from six distinct clinical groups, each with three levels of seniority (early-stage, mid-stage and later-stage career). Changes in the accuracy, confidence and speed of reporting will be compared with and without AI support. Readers will use a secure web-based DICOM (Digital Imaging and Communications in Medicine) viewer (www.raiqc.com), allowing radiograph viewing and abnormality identification. Pooled analyses will be reported for overall reader performance as well as for subgroups including clinical role, level of seniority, pathological finding and difficulty of image.Ethics and dissemination The study has been approved by the UK Healthcare Research Authority (IRAS 310995, approved on 13 December 2022). The use of anonymised retrospective radiographs has been authorised by OUH NHS Foundation Trust. The results will be presented at relevant conferences and published in a peer-reviewed journal.Trial registration numbers This study is registered with ISRCTN (ISRCTN19562541) and ClinicalTrials.gov (NCT06130397). The paper reports the results of a substudy of STEDI2 (Simulation Training for Emergency Department Imaging Phase 2).

Involving addition of chemical groups or protein units to specific residues of the target protein, post-translational modifications (PTMs) alter the charge, hydrophobicity, and conformation of a protein, which in turn influences protein function, protein–protein interaction, and protein aggregation. These alterations, which include phosphorylation, glycosylation, ubiquitination, methylation, acetylation, lipidation, and lactylation, are significant biological events in the development of cancer, and play vital roles in numerous biological processes. The processes behind essential functions, the screening of clinical illness signs, and the identification of therapeutic targets all depend heavily on further research into the PTMs. This review outlines the influence of several PTM types on prostate cancer (PCa) diagnosis, therapy, and prognosis in an effort to shed fresh light on the molecular causes and progression of the disease.

Summary: Erythropoietin-producing hepatoma (Eph) receptors, comprising the largest family of receptor tyrosine kinases (RTKs), exert profound influence on diverse biological processes and pathological conditions such as cancer. Interacting with their corresponding ligands, erythropoietin-producing hepatoma receptor interacting proteins (Ephrins), Eph receptors regulate crucial events like embryonic development, tissue boundary formation, and tumor cell survival. In addition to their well-established roles in embryonic development and cancers, emerging evidence highlights the pivotal contribution of the Ephrin/Eph family to cardiovascular physiology and pathology. Studies have elucidated their involvement in cardiovascular development, atherosclerosis, postnatal angiogenesis, and, more recently, cardiac fibrosis and calcification, suggesting a promising avenue for therapeutic interventions in cardiovascular diseases. There remains a need for a comprehensive synthesis of their collective impact in the cardiovascular context. By exploring the intricate interactions between Eph receptors, ephrins, and cardiovascular system, this review aims to provide a holistic understanding of their roles and therapeutic potential in cardiovascular health and diseases.

Background Anaemia is a severe and common complication in patients with aneurysmal subarachnoid haemorrhage (aSAH). Early intervention for at-risk patients before anaemia occurs is indicated as potentially beneficial, but no validated method synthesises patients’ complicated clinical features into an instrument. The purpose of the current study was to develop and externally validate a nomogram that predicted postacute phase anaemia after aSAH.Methods We developed a novel nomogram for aSAH patients to predict postacute phase anaemia (3 days after occurrence of aSAH, prior to discharge) on the basis of demographic information, imaging, type of treatment, aneurysm features, blood tests and clinical characteristics. We designed the model from a development cohort and tested the nomogram in external and prospective validation cohorts. We included 456 aSAH patients from The First Affiliated Hospital for the development, 220 from Sanmen People’s Hospital for external validation and a prospective validation cohort that included 13 patients from Hangzhou Red Cross Hospital. We assessed the performance of the nomogram via concordance statistics and evaluated the calibration of predicted anaemia outcome with observed anaemia occurrence.Results Variables included in the nomogram were age, treatment method (open surgery or endovascular therapy), baseline haemoglobin level, fasting blood glucose level, systemic inflammatory response syndrome score on admission, Glasgow Coma Scale score, aneurysm size, prothrombin time and heart rate. In the validation cohort, the model for prediction of postacute phase anaemia had a c-statistic of 0.910, with satisfactory calibration (judged by eye) for the predicted and reported anaemia outcome. Among forward-looking forecasts, our predictive model achieved an 84% success rate, which showed that it has some clinical practicability.Conclusions The developed and validated nomogram can be used to calculate individualised anaemia risk and has the potential to serve as a practical tool for clinicians in devising improved treatment strategies for aSAH.

BackgroundThrough preoperative localization, surgeons can easily locate ground glass nodules (GGNs) and effectively control the extent of resection. Therefore, it is necessary to choose an appropriate puncture positioning method. The purpose of this study was to evaluate the effectiveness and safety of medical glue and positioning hooks in the preoperative positioning of GGNs and to provide a reference for clinical selection.MethodsFrom March 30, 2020 to June 13, 2022, a total of 859 patients with a CT diagnosis of GGNs requiring surgical resection were included in our study at the hospital. Among them, 21 patients who either opted out or could not undergo preoperative localization for various reasons were excluded. Additionally, 475 patients who underwent preoperative localization using medical glue and 363 patients who underwent preoperative localization through positioning hooks were also excluded. We conducted statistical analyses on the baseline data, success rates, complications, and pathological results of the remaining patients. The success rates, complication rates, and pathological results were compared between the two groups—those who received medical glue localization and those who received positioning hook localization.ResultsThere was no statistically significant difference between the two groups of patients in terms of age, body mass index, smoking history, location of the nodule, distance of the nodule from the pleura, or postoperative pathological results (P > 0.05). The success rate of medical glue and positioning hooks was 100%. The complication rates of medical glue and positioning hooks during single nodule positioning were 39.18% and 23.18%, respectively, which were significantly different (p < 0.001); the complication rates during multiple nodule positioning were 49.15% and 49.18%, respectively, with no statistically significant differences (p > 0.05). In addition, the method of positioning and the clinical characteristics of the patients were not found to be independent risk factors for the occurrence of complications. The detection rate of pulmonary nodules also showed some positive correlation with the spread of COVID-19 during the 2020–2022 period when COVID-19 was prevalent.ConclusionWhen positioning a single node, the safety of positioning hooks is greater than when positioning multiple nodes, the safety of medical glue and positioning hooks is comparable, and the appropriate positioning method should be chosen according to the individual situation of the patient.

Osteoporotic bone defect repair is one of the challenges in orthopedics because there are no preferable biomaterials to readily initiate new bone regeneration in critical-size pathological bone damage. Our previous studies revealed that core–shell Ca-phosphate/silicate microspheres can tune time-evolving biodegradation, which is beneficial for modulating bone repair. Herein, we expanded this strategy to develop core–shell-type 5 % Sr- and 8 % Zn-doped wollastonite fiber-derived granules with different porosities (0 %, 10 %, 20 %) in the shell layer. Physicochemical analyses indicated that granules with higher porosity in the shell layer exhibited more appreciable Sr and Zn ion release and biodissolution in vitro. Osteoporotic femoral bony defects in rabbits were used to verify the osteogenic efficacy of the core–shell granules. The granules with 10 % porosity could initiate more osteogenesis within 6 weeks, and the new bone tissue could grow into the defect region, while the new bone tissue only migrated into the periphery pores under the other granule conditions. Histological evaluation also revealed appreciable new bone ingrowth in the granules with 10 % porosity, whereas the other implant groups had limited new bone tissue. These findings demonstrate that bone repair initiation can be enhanced by finely designed local porosity in specific components of core–shell bioceramic fiber-tailoring granules to control bioactive ion release and osteo-stimulation in vivo; moreover, such bioceramic fabrication is promising for developing osteo-stimulative implants to resolve clinically challenging bone defect repair.

Abstract Background Klebsiella variicola is considered a newly emerging human pathogen. Clinical isolates of carbapenemase and broad-spectrum β-lactamase-producing K. variicola remain relatively uncommon. A strain of K. variicola 4253 was isolated from a clinical sample, and was identified to carry the bla IMP−4 and bla SFO−1 genes. This study aims to discern its antibiotic resistance phenotype and genomic characteristics. Methods Species identification was conducted using MALDI-TOF/MS. PCR identification confirmed the presence of the bla IMP−4 and bla SFO−1 genes. Antibiotic resistance phenotype and genomic characteristics were detected by antimicrobial susceptibility testing and whole-genome sequencing. Plasmid characterization was carried out through S1-PFGE, conjugation experiments, Southern blot, and comparative genomic analysis. Results K. variicola 4253 belonged to ST347, and demonstrated resistance to broad-spectrum β-lactamase drugs and tigecycline while being insensitive to imipenem and meropenem. The bla IMP−4 and bla SFO−1 genes harbored on the plasmid p4253-imp. The replicon type of p4253-imp was identified as IncHI5B, representing a multidrug-resistant plasmid capable of horizontal transfer and mediating the dissemination of drug resistance. The bla IMP−4 gene was located on the In809-like integrative element (Intl1-bla IMP−4 -aacA4-catB3), which circulates in Acinetobacter and Enterobacteriaceae. Conclusions This study reports the presence of a strain of K. variicola, which is insensitive to tigecycline, carrying a plasmid harboring bla IMP−4 and bla SFO−1. It is highly likely that the strain acquired this plasmid through horizontal transfer. The bla IMP−4 array (Intl1-bla IMP−4 -aacA4-catB3) is also mobile in Acinetobacter and Enterobacteriaceae. So it is essential to enhance clinical awareness and conduct epidemiological surveillance on multidrug-resistant K. variicola, conjugative plasmids carrying bla IMP−4 , and the In809 integrative element.

With the intelligentization of the Internet of Vehicles (IoVs), Artificial Intelligence (AI) technology is becoming more and more essential, especially deep learning. Federated Deep Learning (FDL) is a novel distributed machine learning technology and is able to address the challenges like data security, privacy risks, and huge communication overheads from big raw data sets. However, FDL can only guarantee data security and privacy among multiple clients during data training. If the data sets stored locally in clients are corrupted, including being tampered with and lost, the training results of the FDL in intelligent IoVs must be negatively affected. In this paper, we are the first to design a secure data auditing protocol to guarantee the integrity and availability of data sets in FDL-empowered IoVs. Specifically, the cuckoo filter and Reed-Solomon codes are utilized to guarantee error tolerance, including efficient corrupted data locating and recovery. In addition, a novel data structure, Skip Hash Table (SHT) is designed to optimize data dynamics. Finally, we illustrate the security of the scheme with the Computational Diffie-Hellman (CDH) assumption on bilinear groups. Sufficient theoretical analyses and performance evaluations demonstrate the security and efficiency of our scheme for data sets in FDL-empowered IoVs.

Abstract This study examines a collaborative framework that utilizes an intelligent deep Q-network to regulate the formation of leader–follower Unmanned Aerial Vehicles (UAVs). The aim is to tackle the challenges posed by the highly dynamic and uncertain flight environment of UAVs. In the context of UAVs, we have developed a dynamic model that captures the collective state of the system. This model encompasses variables like as the relative positions, heading angle, rolling angle, and velocity of different nodes in the formation. In the subsequent section, we elucidate the operational procedure of UAVs in a collaborative manner, employing the conceptual framework of Markov Decision Process (MDP). Furthermore, we employ the Reinforcement Learning (RL) to facilitate this process. In light of this premise, a fundamental framework is presented for addressing the control problem of UAVs utilizing the DQN scheme. This framework encompasses a technique for action selection known as $$\varepsilon$$ ε -imitation, as well as algorithmic specifics. Finally, the efficacy and portability of the DQN-based approach are substantiated by numerical simulation validation. The average reward curve demonstrates a satisfactory level of convergence, and kinematic link between the nodes inside the formation satisfies the essential requirements for the creation of a controller.

Abstract Background Thrombotic thrombocytopenic purpura (TTP) is a rare thrombotic microangiopathy with a rapid progression and high mortality rate. We aimed to explore early risk factors for mortality in patients with TTP. Methods We conducted a retrospective analysis of 42 TTP patients that were admitted to our hospital between 2000 and 2021, with a median age of 49 (29–63) years. Risk factors for mortality were evaluated using multivariate logistic regression. Receiver operating characteristic curve analysis was used to determine the cut-off value of glucose for predicting mortality in patients, which was validated by comparison to a similar cohort in the published literature. Results Elevated glucose level and reduced red blood cells (RBC) counts were risk factors for mortality in patients with TTP (glucose, odds ratio and 95% confidence interval: 2.476 [1.368–4.484]; RBC, odds ratio and 95% confidence interval: 0.095 [0.011–0.799]). The area under the curve of glucose was 0.827, and the cut-off value was 9.2 mmol/L, with a sensitivity of 75.0% and specificity of 95.8%. A total of 26 cases from the validation cohort had a sensitivity of 71.0% and a specificity of 84.0%. The change trends of the TTP-related laboratory indices differed during hospitalization. Conclusion Hyperglycemia at admission and unstable blood glucose levels during hospitalization may be potential predictors of mortality for TTP patients. The improved prognosis was associated with the recovery of platelet counts and a significant decrease in serum lactate dehydrogenase after five days of treatment.

This paper addresses the problem of high communication frequency in the multi-rotor unmanned aerial vehicles swarm system. A novel sliding mode control method based on event-triggering is proposed, using a dual-loop structure control model based on sliding mode control of multi-rotor UAVs swarm. The model consists of a position subsystem and an attitude subsystem, where the position subsystem serves as the outer loop control object, and the attitude subsystem serves as the inner loop auxiliary control object. In the position subsystem, a sliding mode controller with event triggers is used to achieve position control of the multi-rotor UAVs swarm by introducing sliding mode surfaces and sliding mode variables. The stability of the system under this control strategy is proved by the Lyapunov stability theorem, and the absence of the Zero phenomenon is also proved. Simulation results demonstrate that the proposed control scheme reduces the reliance on high-frequency sampling of multi-rotor UAVs communication. This research provides a useful reference for the application of multi-rotor UAVs swarms in collaborative path following.

Reduction of endogenous hydrogen sulfide (H2S) is considered to have an important impact on the progress of Parkinson's disease (PD), thus exogenous H2S supplementation is expected to become one of the key means to treat PD. However, at present, it is difficult for H2S donors to effectively penetrate the blood brain barrier (BBB), selectively release H2S in brain, and effectively target the mitochondria of neuron cells. Herein, we report a kind of nanomotor-based H2S donor, which is obtained by free radical polymerization reaction between l-cysteine derivative modified-polyethylene glycol (PEG-Cys) and 2-methacryloyloxyethyl phosphorylcholine (MPC). This kind of H2S donor can not only effectively break through BBB, but also be specifically catalyzed by cystathionine β-synthase (CBS) in neurons of PD site in brain and 3-mercaptopyruvate sulfurtransferase (3-MST) in mitochondria to produce H2S, endowing it with chemotaxis/motion ability. Moreover, the unique chemotaxis effect of nanomotor can realize the purpose of precisely targeting brain and the mitochondria of damaged neuron cytopathic diseases. This kind of nanomotor-based H2S donor is expected to enrich the current types of H2S donors and provide new ideas for the treatment of PD.

Nitric oxide (NO) and hydrogen sulfide (H2S) gasotransmitters exhibit potential therapeutic effects in the cardiovascular system. Herein, biomimicking multilayer structures of biological blood vessels, bilayer small-diameter vascular grafts (SDVGs) with on-demand NO and H2S release capabilities, were designed and fabricated. The keratin-based H2S donor (KTC) with good biocompatibility and high stability was first synthesized and then electrospun with poly (l-lactide-co-caprolactone) (PLCL) to be used as the outer layer of grafts. The electrospun poly (ε-caprolactone) (PCL) mats were aminolyzed and further chelated with copper (II) ions to construct glutathione peroxidase (GPx)-like structural surfaces for the catalytic generation of NO, which acted as the inner layer of grafts. The on-demand release of NO and H2S selectively and synergistically promoted the proliferation and migration of human umbilical vein endothelial cells (HUVECs) while inhibiting the proliferation and migration of human umbilical artery smooth muscle cells (HUASMCs). Dual releases of NO and H2S gasotransmitters could enhance their respective production, resulting in enhanced promotion of HUVECs and inhibition of HUASMCs owing to their combined actions. In addition, the bilayer grafts were conducive to forming endothelial cell layers under flow shear stress. In rat abdominal aorta replacement models, the grafts remained patency for 6 months. These grafts were capable of facilitating rapid endothelialization and alleviating neointimal hyperplasia without obvious injury, inflammation, or thrombosis. More importantly, the grafts were expected to avoid calcification with the degradation of the grafts. Taken together, these bilayer grafts will be greatly promising candidates for SDVGs with rapid endothelialization and anti-calcification properties.

Metal-catalyzed cyclization reactions have become a powerful and efficient approach for the stereoselective construction of both carbocyclic and heterocyclic ring systems. Transition metal complexes, with their ability to activate and selectively functionalize organic substrates, have revolutionized various areas of synthetic chemistry. This review highlights recent advancements in metal-catalyzed cyclization reactions, especially in the synthesis of nitrogen-containing heterocycles like imidazoles, pyridines, pyrimidines, and indoles. These advancements have significantly impacted fields such as natural product synthesis, pharmaceuticals, functional materials, and organic electronics. Novel catalytic systems, ligand designs, and reaction conditions continue to expand the capabilities of these reactions, driving further the progress made in synthetic organic chemistry. This review provides a comprehensive overview of recent research.

To address the challenges of labor-intensive and costly manual oyster spat insertion in longline-suspended farming, an automated oyster spat insertion device was designed based on negative pressure suction and bundling fixation technologies. Using this device as the experimental platform, a three-factor, three-level Box–Behnken experiment was conducted, with fixation mechanism inclination, negative pressure suction cup span, and horizontal distance between turnover and fixation mechanisms as the experimental factors. The performance of the device was evaluated using the effective fixation rate and damage rate as the experimental indicators. The quadratic polynomial regression models were established to assess the impact of these factors on operational performance, while the response surface method was employed to analyze the interaction effects between factors. Parameter optimization and experimental validation were also performed. The results indicate that the factors affecting the effective fixation rate, in order of significance, are as follows: fixation mechanism inclination, horizontal distance between turnover and fixation mechanisms, and negative pressure suction cup span. For the damage rate, the order of significance is as follows: fixation mechanism inclination > negative pressure suction cup span < horizontal distance between turnover and fixation mechanisms. The optimization results show that when the fixation mechanism inclination is set at 43°, the negative pressure suction cup span at 27 mm, and the horizontal distance between turnover and fixation mechanisms at 179 mm, the effective fixation rate reaches 92.08%, and the damage rate is 4.71%. The relative errors between the measured and model-predicted values are less than 5%, indicating that the regression models are reliable. This research provides valuable insights for advancing the mechanization of the oyster farming industry and replacing manual labor with mechanized equipment.

Objective: To assess acceptability and feasibility of rapid at-home COVID-19 testing and reporting of test results among individuals seeking care at community health centers (CHCs) and their household members. Methods: Participants were recruited from 2 Community Health Centers during a clinic visit or a community event. Over-the-counter COVID-19 tests were distributed to participants for self-testing and to offer testing to household members. Separate surveys were administered to collect baseline information on the study participant and to collect test results on the study participant and household members. We calculated the proportion of individuals who agreed to complete COVID home testing, those who reported test results, and the test positivity. For household members, we calculated the proportion who completed and reported results and the positivity rate. We assessed reasons for undergoing COVID-19 testing and the action taken by participants who reported positive tests. Results: A total of 2189 individuals were approached by CHC staff for participation and 1013 (46.3%) agreed to participate. Among the 959 participants with complete sociodemographic data, 88% were Hispanic and 82.6% were female. The proportion providing test results was 36.2% and the test positivity was 4.2%. Among the 1927 test reports, 35.3% for the index participant and 64.4% were for household members. The largest proportion of test results were for index participants (35.3%) and the second largest was for the participant’s children (32.1%), followed by parents (16.9%), and spouse/partner (13.2%). The 2 most common reasons for testing were symptoms (29%) and attending family gatherings (26%). Among test-positive individuals (n = 80), most (83.3%) noted that they isolated but only 16.3% called their provider and 1.3% visited a clinic. Conclusion: Our results show interest in at-home COVID-19 testing of multiple household members, as we headed into the endemic phase of the pandemic. However, reporting of test results was modest and among test-positive individuals, reporting results to a provider was very low. These results underscore the challenges with reporting and following guidelines among people undergoing home testing for COVID-19, which may have implications for future pandemics.

Morphological changes in estuaries are typically discussed on decadal time scales, with reported changes often exceed several decimeters. In our study, we utilized refined in-situ data to investigate bed-level changes and rapid accretion-erosion transitions during tidal cycles off the Changjiang Estuary. A field study employing a high-resolution bottom tripod system was conducted, measuring various parameters such as water level, waves, velocity profiles, near-bottom suspended sediment concentration (SSC), and bed level changes over ten tidal cycles. Our findings reveal significant and intense bed level changes occurring at the scale of tidal cycles. The data suggests that downward sediment transport plays a dominant role in the overall accretion tendency throughout the study period. Additionally, our research introduces a dynamic critical bed shear stress that increases during tidal cycles, deviating from fixed values. We also present a new quadrant analysis method to elucidate the primary processes controlling near-bed sediment transport. The results highlight the importance of horizontal advective sediment transport in frequent accretion-erosion transitions at tidal-cycle timescales. This implies a frequent exchange of sediment between adjacent shoals and channels in the seaward region of the North Channel in the Changjiang Estuary, which holds significance for future navigation and construction management.

This study explores the development of an innovative Fabry-Perot Interferometer (FPI) designed for temperature sensing and environmental monitoring. The device is constructed by embedding optical fibers within a 3D-printed resin scaffold, forming a structure with an open Fabry-Perot cavity. Intended as an integral component of Cyber-Physical-Social Systems (CPSS), this FPI structure aims to enhance the system’s capacity to sense changes in external environmental conditions. Within the CPSS context, the FPI offers several advantages, including simple manufacturing processes, low production costs, and high sensitivity. These benefits contribute to providing precise environmental feedback to the system, which is essential in implementing effective security and privacy protection strategies. Experimental evaluations have shown that the FPI exhibits a high linear sensitivity of 14.330 nm/°C within a temperature range of 34.9°C–38.5°C, confirming its potential for application in CPSS for temperature monitoring and environmental sensing.

Abstract Molecular subtyping of lung squamous cell carcinoma (LUSC) has been performed at the genomic, transcriptomic, and proteomic level. However, LUSC stratification based on tissue metabolomics is still lacking. Combining high-mass-resolution imaging mass spectrometry with consensus clustering, four tumor- and four stroma-specific subtypes with distinct metabolite patterns were identified in 330 LUSC patients. The first tumor subtype T1 negatively correlated with DNA damage and immunological features including CD3, CD8, and PD-L1. The same features positively correlated with the tumor subtype T2. Tumor subtype T4 was associated with high PD-L1 expression. Compared with the status of subtypes T1 and T4, patients with subtype T3 had improved prognosis, and T3 was an independent prognostic factor with regard to UICC stage. Similarly, stroma subtypes were linked to distinct immunological features and metabolic pathways. Stroma subtype S4 had a better prognosis than S2. Subsequently, analyses based on an independent LUSC cohort treated by neoadjuvant therapy revealed that the S2 stroma subtype was associated with chemotherapy resistance. Clinically relevant patient subtypes as determined by tissue-based spatial metabolomics are a valuable addition to existing molecular classification systems. Metabolic differences among the subtypes and their associations with immunological features may contribute to the improvement of personalized therapy.

Abstract Animals living in high‐altitude environments, such as the Tibetan Plateau, must face harsh environmental conditions (e.g., hypoxia, cold, and strong UV radiation). These animals' physiological adaptations (e.g., increased red cell production and turnover rate) might also be associated with the gut microbial response. Bilirubin is a component of red blood cell turnover or destruction and is excreted into the intestine and reduced to urobilinoids and/or urobilinogen by gut bacteria. Here, we found that the feces of macaques living in high‐altitude regions look significantly browner (with a high concentration of stercobilin, a component from urobilinoids) than those living in low‐altitude regions. We also found that gut microbes involved in urobilinogen reduction (e.g., beta‐glucuronidase) were enriched in the high‐altitude mammal population compared to the low‐altitude population. Moreover, the spatial–temporal change in gut microbial function was more profound in the low‐altitude macaques than in the high‐altitude population, which might be attributed to profound changes in food resources in the low‐altitude regions. Therefore, we conclude that a high‐altitude environment's stress influences living animals and their symbiotic microbiota.

With quantum computers, the quantum resistance of cryptographic systems has gradually attracted attention. To overcome the shortcoming of existing identity-based encryption (IBE) schemes in resisting quantum attacks, we introduce an IBE scheme based on learning with errors (LWE). In addition, devices with limited computing power are becoming increasingly common in practice, making it increasingly important to improve the efficiency of online computation of encryption algorithms. The classic solution is to directly improve the efficiency of the Gaussian sampling algorithm, thereby increasing the overall efficiency of the scheme. However, our scheme combines the efficient Gaussian sampling algorithm, G-trapdoor, with online/offline method to further improve the online encryption efficiency of the encryption algorithm. Our scheme completes partial computation before knowing the message and receiver’s identity, and once the message and receiver’s identity are obtained, the online part encryption can be efficiently completed. We construct an identity-based online/offline encryption (IBOOE) scheme from LWE with G-trapdoor, improve the efficiency of online encryption while achieving quantum resistant security. We prove the scheme’s security under the standard model for chosen-plaintext attack (CPA). By comparing with relevant schemes in terms of experiments and analysis, our scheme has improved efficiency by 65% to 80% compared to the classical LWE IBE scheme (increasing with LWE security parameters), and by 60% to 70% compared to the recent IBE scheme from LWE. This greatly improves the efficiency of online computing for low-power encryption devices while ensuring security.

Abstract Electro-optic modulators are key components in data communication, microwave photonics, and quantum photonics. Modulation bandwidth, energy efficiency, and device dimension are crucial metrics of modulators. Here, we provide an important direction for the miniaturization of electro-optic modulators by reporting on ultracompact topological modulators. A topological interface state in a one-dimensional lattice is implemented on a thin-film lithium-niobate integrated platform. Due to the strong optical confinement of the interface state and the peaking enhancement of the electro-optic response, a topological cavity with a size of 1.6 × 140 μm2 enables a large modulation bandwidth of 104 GHz. The first topological modulator exhibits the most compact device size compared to reported LN modulators with bandwidths above 28 GHz, to the best of our knowledge. 100 Gb/s non-return-to-zero and 100 Gb/s four-level pulse amplitude modulation signals are generated. The switching energy is 5.4 fJ/bit, owing to the small electro-optic mode volume and low capacitance. The topological modulator accelerates the response time of topological photonic devices from the microsecond order to the picosecond order and provides an essential foundation for the implementation of large-scale lithium-niobate photonic integrated circuits.

The threshold pressure gradient (TPG) of gas-liquid seepage in tight sandstone varies with the rock effective stress, that is, the dynamic threshold pressure gradient effect, its dynamic variation characteristics are controlled by the pore-throat structure. In order to explore the characteristics of dynamic TPG of reservoirs in the process of multi-layer co-injection CO2 development in coal-measure tight sandstone reservoirs, the TPG tests were conducted on cores with different physical properties at different effective stress. The influence of rock pore-throat structure and permeability on the dynamic TPG was quantitatively studied based on the fractal analysis method, the calculation method of dynamic TPG was established. The dynamic and fixed threshold pressures and the corresponding gas productivity loss in reservoirs during CO2 injection were calculated. The experimental results show that the effective stress of tight rocks increased from 1 MPa to 29 MPa, and TPG showed a logarithmic increasing trend with effective stress, with an increase range of 31.2%−120.1%. The TPG value depended on the rock permeability at low stress and showed a power-decreasing trend with permeability. The fractal dimension of the pore-throat structure controlled the dynamic TPG stress sensitivity. The fractal dimension of the rock pore-throat structure and the TPG sensitivity coefficient showed a power-increasing trend. The larger injection pressure and smaller spacing between injection and production wells could reduce the additional pressure consumption caused by dynamic threshold pressure, and reduce the interlayer interference during CO2 co-injection. The calculated minimum effective injection pressure of the reservoir was 32.8%−69.6% lower according to the fixed TPG. The more complex the pore-throat structure of the reservoir, the greater the deviation of the estimated value. When the injection pressure increased to 29 MPa, the dynamic threshold pressure decreased by 3.4−7.4 MPa, and the additional pressure loss caused by the dynamic threshold pressure was 1.0−5.8 MPa. The differences in the sweep range of injected CO2 under the influence of dynamic and fixed TPG under the same injection pressure were 40.5%−51.3%. The reservoir productivity loss caused by TPG at maximum injection pressure was 24.6%−65.3%, which was 4.1%−21.1% higher than the fixed TPG. The more complex the pore-throat structure of reservoir rock was, and the lower the injection pressure, the greater the difference in productivity loss caused by dynamic threshold pressure. In the development of multi-layer CO2 co-injection in the coal-measure tight sandstone reservoir, the reservoir pressure should be prevented from weakening to a lower reservoir pressure value. A larger injection pressure and a smaller injection-production well spacing should be adopted to reduce the additional production capacity loss caused by the dynamic TPG effect, at the same time, the interference between layers should be mitigated to improve the multi-layer CO2 co-injection development effect.

Abstract Obesity/overweight and lipid metabolism disorders have become increased risk factors for lung cancer. Fatty acid translocase CD36 promotes cellular uptake of fatty acids. Whether and how CD36 facilitates lung adenocarcinoma (LUAD) growth in high-fat environment is unknown. Here, we demonstrated that palmitic acid (PA) or high-fat diet (HFD) promoted LUAD cell proliferation and metastasis in a CD36-dependent manner. Mechanistically, CD36 translocated from cytoplasm to cell membrane and interacted with Src kinase upon PA stimulation in human LUAD cells. Akt and ERK, downstream of Src, were then activated to mediate LUAD cell proliferation and metastasis. Furthermore, PA treatment promoted CD36 sarcolemmal translocation, where it activated Rac1 and upregulated MMP-9 through Src-Akt/ERK pathway, resulting in redistribution of cortactin, N-WASP and Arp2/3, and finally led to occurrence of finger-like protrusions of actin on cell surface to enhance cell metastasis. Compared with normal-chew diet (NCD) mice, the HFD group exhibited higher level of blood free fatty acid (FFA) and cholesterol (TC), developed larger xenograft LUAD tumors and enhanced tumor cell metastatic potential, which were accompanied by obvious sarcolemmal actin remodeling and were blocked by simultaneous CD36 knockdown in LUAD cells. Consistently, xenografted and tail vein-injected scramble-RNA-A549 cells but not CD36-shRNA-A549 in HFD mice formed metastatic LUAD tumors on the lung. CD36 inhibitor SSO significantly inhibited LUAD cell metastasis to the lung. Collectively, CD36 initiates Src signaling to promote LUAD cell proliferation and actin remodeling-involved metastasis under high-fat environment. Our study provides the new insights that CD36 is a valid target for LUAD therapy.

In order to explore a kind of hot-air drying of Antarctic krill under variable temperature process, the drying time, protein, fat and astaxanthin content were taken as indicators, the effects of first phase of the drying temperature, second phase of the drying temperature and moisture content point on the drying effect of Antarctic krill were studied, the drying effect was evaluated by multi-index comprehensive scoring method, the drying technology of dried Antarctic krill was optimized by orthogonal optimization test based on single factor experiments. The results showed that the optimum hot-air drying of Antarctic krill under variable temperature process were first phase of the drying temperature 55 ℃, second phase of the drying temperature 85 ℃, moisture content point 50%. The dried Antarctic krill obtained by this optimized process were the content of protein, fat, astaxanthin and drying time 69.24%, 19.79%, 232.72 μg/g, 300 min, respectively, and the comprehensive score of drying effect was 99.05.

Abstract A high‐resolution wave model is crucial for accurate modeling of sediment and organic material transports, but its computational costs hinder direct coupling to an ecosystem model. We developed a machine learning model using long short‐term memory to simulate large‐scale, high‐resolution waves. Trained with numerical wave model (NWM) outputs and wind data from nine locations, our model successfully replicates NWM results for daily mean significant wave height and period in Chesapeake Bay with identical spatial resolution. Compared to the NWM, the data‐driven model has root‐mean‐square errors below 6 cm for daily mean significant wave height and 1 s for the wave period in the bay. It demonstrates excellent model skills and can accurately forecast daily mean significant wave height and period at NOAA wave stations comparable to NWMs. Using minimal wind data and having a short runtime, our data‐driven model shows promise as an alternative for wave forecasting and coupling with sediment and ecological models.

Cell death is ubiquitous during development and throughout life and is a genetically determined active and ordered process that plays a crucial role in regulating homeostasis. Cell death includes regulated cell death and non-programmed cell death, and the common types of regulatory cell death are necrosis, apoptosis, necroptosis, autophagy, ferroptosis, and pyroptosis. Apoptosis, Necrosis and necroptosis are more common than autophagy, ferroptosis and pyroptosis among cell death. Non-coding RNAs are regulatory RNA molecules that do not encode proteins and include mainly microRNAs, long non-coding RNAs, and circular RNAs. Non-coding RNAs can act as oncogenes and tumor suppressor genes, with significant effects on tumor occurrence and development, and they can also regulate tumor cell autophagy, ferroptosis, and pyroptosis at the transcriptional or post-transcriptional level. This paper reviews the recent research progress on the effects of the non-coding RNAs involved in autophagy, ferroptosis, and pyroptosis on tumorigenesis, tumor development, and treatment, and looks forward to the future direction of this field, which will help to elucidate the molecular mechanisms of tumorigenesis and tumor development, as well as provide a new vision for the treatment of tumors.

Introduction Radiographic bone age (BA) assessment is widely used to evaluate children’s growth disorders and predict their future height. Moreover, children are more sensitive and vulnerable to X-ray radiation exposure than adults. The purpose of this study is to develop a new, safer, radiation-free BA assessment method for children by using three-dimensional ultrasound (3D-US) and artificial intelligence (AI), and to test the diagnostic accuracy and reliability of this method.Methods and analysis This is a prospective, observational study. All participants will be recruited through Paediatric Growth and Development Clinic. All participants will receive left hand 3D-US and X-ray examination at the Shanghai Sixth People’s Hospital on the same day, all images will be recorded. These image related data will be collected and randomly divided into training set (80% of all) and test set (20% of all). The training set will be used to establish a cascade network of 3D-US skeletal image segmentation and BA prediction model to achieve end-to-end prediction of image to BA. The test set will be used to evaluate the accuracy of AI BA model of 3D-US. We have developed a new ultrasonic scanning device, which can be proposed to automatic 3D-US scanning of hands. AI algorithms, such as convolutional neural network, will be used to identify and segment the skeletal structures in the hand 3D-US images. We will achieve automatic segmentation of hand skeletal 3D-US images, establish BA prediction model of 3D-US, and test the accuracy of the prediction model.Ethics and dissemination The Ethics Committee of Shanghai Sixth People’s Hospital approved this study. The approval number is 2022-019. A written informed consent will be obtained from their parent or guardian of each participant. Final results will be published in peer-reviewed journals and presented at national and international conferences.Trial registration number ChiCTR2200057236.