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Abstract Engineered bacteria‐mediated antitumor approaches have been proposed as promising immunotherapies for cancer. However, the off‐target bacterial toxicity narrows the therapeutic window. Living microbes will benefit from their controllable immunogenicity within tumors for safer antitumor applications. In this study, a genetically encoded microbial activation strategy is reported that uses tunable and dynamic expression of surface extracellular polysaccharides to improve bacterial biocompatibility while retaining therapeutic efficacy. Based on screening of genes associated with Salmonella survival in macrophages, a novel attenuated Salmonella chassis strain AIS (htrA gene‐deficient) highly enriched in tumors after administration and rapidly cleared from normal organs are reported. Subsequently, an engineered bacterial strain, AISI‐H, is constructed based on the AIS strain and an optimized quorum‐sensing regulatory system. The AISI‐H strain can achieve recovery of dynamic tumor‐specific bacterial virulence through a novel HTRA‐RCSA axis‐based and quorum‐sensing synthetic gene circuit‐mediated increase in extracellular polysaccharide content. These strains act “off” in normal organs to avoid unwanted immune activation and “on” in tumors for precise tumor suppression in mice. The AISI‐H strain shows significant tumor inhibition and potent activation of anticancer immunity in a melanoma mouse model. The AISI‐H strain exhibits excellent biocompatibility. This bacterial regulation strategy expands the applications of microbe‐based antitumor therapeutics.

ABSTRACT Aim This study aims to investigate the association of glycemia risk index (GRI), a novel composite metric derived from continuous glucose monitoring (CGM), with arterial stiffness in patients with type 2 diabetes. Materials and Methods A total of 342 adults with type 2 diabetes were enrolled between April and June 2023 from 11 communities in Shanghai, China. Medical examinations, including measurements of anthropometric parameters, blood pressure, and venous blood samples were conducted. Brachial‐ankle pulse wave velocity (baPWV) was examined to evaluate arterial stiffness. All the participants underwent a 14 day CGM recording and GRI was calculated from the CGM data. Results The mean age was 70.3 ± 6.8 years, and 162 (47.4%) were male. Participants with a higher baPWV had significantly higher levels of GRI and hyperglycemia component (both P for trend

Abstract To investigate the imaging manifestations and pathological features of ocular adnexal lymphoma (OALs) in order to provide relevant information for ophthalmologists. A total of 94 patients with OALs were pathologically confirmed between August 2018 and July 2023, and their demographics, location, subtype, treatment, and prognosis were retrospectively studied. 94 patients with OALs were included in this study, of whom 28 were female (29.79%) and 66 were male (70.21%). The age of the patients ranged from 21 to 80 years, with a predominance of 50–60 years (60/94); monocular onset was common (90/94), and the most site of onset was orbital (74/94), followed by conjunctiva (12/94), eyelids (4/94), vitreous (3/94), and lacrimal gland (1/94). CT and MRI can show the involvement and extent of the lesions, and the pathology of the disease is characterized by mucosa‐associated lymphoid tissue marginal zone B‐cell lymphoma (72/94), diffuse large B‐cell lymphoma (10/94), T‐cell lymphoma (4/94), mantle cell lymphoma (2/94), Burkitt's lymphoma (2/94), small lymphocytic lymphoma (2/94), and follicular lymphoma (1/94). All patients received surgical treatment, 42 patients received local radiation therapy, 35 patients received chemotherapy, 13 patients received radiation therapy and chemotherapy successively, and 3 patients received comprehensive treatment. During the follow‐up, three patients relapsed, four died, one was lost to follow‐up, and the remaining patients had stable conditions. The majority of OALs are mucosa‐associated lymphoid tissue marginal zone B‐cell lymphomas (MALT) with an excellent prognosis. It mostly occurs in people over 50 years of age and most site of the onset is orbital.

Abstract Objective To explore the influence of nutritional status on adverse clinical events in elderly patients with nonvalvular atrial fibrillation. Methods This retrospective observational cohort study included 196 patients, 75–102‐years‐old, with nonvalvular atrial fibrillation, hospitalized in our hospital. The nutritional status was assessed using Mini‐Nutritional Assessment—Short Form (MNA‐SF). Patients with MNA‐SF scores of 0–11 and 12–14 were included in the malnutrition and nonmalnutrition groups, respectively. Results The average age of the malnutrition group was higher than that of the nonmalnutrition group, and the levels of body mass index (BMI), hemoglobin (HGB), and albumin (ALB) were significantly lower than those of the nonmalnutrition group, with statistical significance (p

Abstract CD47 blockade has emerged as a promising immunotherapy against liver cancer. However, the optimization of its antitumor effectiveness using efficient drug delivery systems or combinations of therapeutic agents remains largely incomplete. Here, patients with liver cancer co‐expressing CD47 and CDC7 (cell division cycle 7, a negative senescence‐related gene) are found to have the worst prognosis. Moreover, CD47 is highly expressed, and senescence is inhibited after the development of chemoresistance, suggesting that combination therapy targeting CD47 and CDC7 to inhibit CD47 and induce senescence may be a promising strategy for liver cancer. The efficacy of intravenously administered CDC7 and CD47 inhibitors is limited by low uptake and short circulation times. Here, inhibitors are coloaded into a dual‐targeted nanosystem. The sequential release of the inhibitors from the nanosystem under acidic conditions first induces cellular senescence and then promotes immune responses. In an in situ liver cancer mouse model and a chemotherapy‐resistant mouse model, the nanosystem effectively inhibited tumor growth by 90.33% and 85.15%, respectively. Overall, the nanosystem in this work achieved the sequential release of CDC7 and CD47 inhibitors in situ to trigger senescence and induce immunotherapy, effectively combating liver cancer and overcoming chemoresistance.

Abstract As water‐related ecosystem services (WRES) encounter unprecedented threats with climate change and human activities, it is important to understand the impact of variations in the supply and demand for WRES on Sustainable Development Goals (SDGs). Previous studies commonly overlooked water quality and water‐use sectors when using comprehensive supply‐demand index (SDIcom), defined as the difference between water supply and demand, leading to challenges in applying WRES estimation to SDGs assessment. We constructed a refined supply‐demand framework for WRES, categorizing the water supply by water quality and the water demand by sectors. It allows the calculation of refined supply‐demand index (SDIref), addressing the limitations of SDIcom. Our findings demonstrate that SDIref could be effectively employed to assess SDGs and rectify the overestimation of SDIcom in the case study in Xinjiang. The supply‐demand relationship of water resources indicates surpluses in domestic and industrial water use and deficits in agricultural and ecological water use, with the latter worsening. SDIref is projected to be higher in the scenario with SSP2‐4.5 and high growth rate of irrigation efficiency. Our study suggested informed decisions based on SDG‐specific targets to either maintain or enhance SDG progress scores. The proposed refined supply‐demand framework of WRES established a quantitative link between WRES and human well‐being, providing applicable insights for other ecosystem service assessments in other regions.

Abstract Creation of new fluorophores is important for understanding the structure–property relationship, by which the required optical properties are likely to be attained. Herein, through theory calculation, it is found that furan‐modified thiadiazolo quinoxaline acting as an electron acceptor can endow donor–acceptor–donor (D–A–D) type second near‐infrared (NIR‐II) fluorophores with longer emission wavelength than the other thiadiazolo quinoxaline‐based acceptors containing pyridine, pyrrole, thiophene, and phenyl groups, respectively. On the basis of this theoretical prediction, a D–A–D type NIR‐II fluorophore with 6,7‐di(furan‐2‐yl)‐[1,2,5]thiadiazolo[3,4‐g] quinoxaline (DFTQ) as the acceptor and dithieno[3,2‐b:2′,3′‐d]pyrrole (DTP) as the donor is designed and synthesized, and the aggregation‐induced emission (AIE) function is further achieved by introducing the AIE units of tetraphenylethylene (TPE) and triphenylamine (TPA), respectively, totally forming three NIR‐II fluorophores DFTQ–DTP, DFTQ–DTPE, and DFTQ–DTPA. For biological applications, the fluorophores are encapsulated by amphiphilic DSPE–PEG2000 to generate water‐dispersible nanoparticles (NPs). Almost the whole emission of each of the NPs falls into the NIR‐II spectral range, with part emission beyond 1300 nm. By using DFTQ–DTPA NPs as the contrast and photothermal therapy (PTT) agent, high‐resolution in vivo fluorescence imaging is achieved in the greater than 1300 nm window, and their good performance in photoacoustic imaging and high tumor PTT efficacy in tumor‐bearing mice are also demonstrated. Taken together, this work mainly provides a strong electron acceptor for constructing long‐emitting fluorophores, and by using the electron acceptor, a AIE fluorophore with desirable quantum yield (QY) and photothermal conversion efficienciy (PCE) is synthesized and demonstrated to be promising in fluorescence/photoacoustic imaging and PTT.

Abstract The integrity of the intestinal mucosal barrier is crucial for protecting the intestinal epithelium against invasion by commensal bacteria and pathogens, thereby combating colitis. The investigation revealed that the absence of TSP50 compromised the integrity of the intestinal mucosal barrier in murine subjects. This disruption facilitated direct contact between intestinal bacteria and the intestinal epithelium, thereby increasing susceptibility to colitis. Mechanistic analysis indicated that TSP50 deficiency in intestinal stem cells (ISCs) triggered aberrant activation of the TGF‐β signaling pathway and impeded the differentiation of goblet cells in mice, leading to impairment of mucosal permeability. By inhibiting the TGF‐β pathway, the functionality of the intestinal mucosal barrier is successfully restored and mitigated colitis in TSP50‐deficient mice. In conclusion, TSP50 played a crucial role in maintaining the intestinal mucosal barrier function and exhibited the preventive effect against the development of colitis by regulating the TGF‐β signaling pathway.

Abstract In island mode, voltage source inverter (VSI) supports the frequency and voltage of microgrid. After the complex load is connected, the VSI control performance is degraded, and the output voltage has deviation, negative sequence, waveform distortion and other problems, which further deteriorate the power quality of the microgrid. Different from the traditional strategy that only focus on a single problem, the strategy proposed in this paper can deal with these three power quality problems simultaneously. In this paper, a self‐learning sliding mode control strategy is proposed. First, a nonlinear smooth function is used to design an expansion observer, which can estimate the expansion state of the internal uncertainties and external disturbances of the control system. Second, the extended observer is combined with the self‐learning synovial control technology to realize the self‐learning synovial disturbance rejection control of VSI control strategy. This strategy can improve the stability of voltage control under various working conditions without precise mathematical model. The simulation results show that, compared with the traditional control strategy, this strategy has good robustness under different working conditions.

Abstract Recently, the applications of cold atmospheric plasma (CAP) in liquid treatment have attracted increasing attention owing to its excellent medical efficacy. It has been proved that CAP can effectively enhance the biological activity of vegetable oils due to the generation of reactive species. Optimising the reactor parameter is an important approach to regulate reactive species in plasma‐activated oil to obtain better biological effects. In this study, a self‐made jet array driven by a pulsed power supply was used to generate large‐area plasma to irradiate perilla seed oil (PSO), with the formation of plasma‐activated perilla seed oil (PAPSO). By means of laser‐induced fluorescence and chemical titration, the relative density of hydroxyl radical radical in plasma jet, as well as the activity of PAPSO were measured under different discharge parameters, and realised the control of the activity of PAPSO. In vitro experiments showed that PAPSO significantly enhanced its ability to inhibit cancer cells proliferation and induce apoptosis after plasma treatment, which provides a reference for cancer treatment. This study is helpful to further understand the influence of plasma dose effect on the activity of media and provide guidance for related plasma medical applications.

Abstract To study the role of Body Mass Index (BMI) and serum lipid profile molecules, as well as their derivative indexes in primary pterygium patients. The patient group consisted of 110 patients with primary pterygium diagnosed in our center between January 2019 and December 2020, while the control group consisted of 144 healthy persons of similar age and sex diagnosed during the same time period. The BMI, serum lipid profile molecules and their derivative indexes of both groups were analyzed retrospectively. In the patient group, 62 patients were overweight or obesity and 104 patients with dyslipidemia. Among them, body mass index (BMI), serum triglycerides (TG), total cholesterol (TC), low‐density lipoprotein cholesterol (LDL‐C) and apolipoprotein B (Apo‐B) levels were significantly higher than those in the control group (p 0.05). Logistic analysis indicated that obesity, TC and HDL‐C/LDL‐C ratio are independent risk factors influencing the onset of pterygium (p

Abstract Future climate projections suggest a poleward shift of the maximum intensity of tropical cyclones (TCs) over the western North Pacific. However, the global nature of the latitudinal change in TC genesis under global warming remains poorly understood. We show, using large‐ensemble high‐resolution atmospheric model simulations (d4PDF) with four warming scenarios, that the poleward shift is a robust change over the globe, attributable to the weakening of the Hadley circulation. The weakened ascent driven by the upper‐tropospheric warming suppresses the TC genesis within 5°–20° latitudes, whereas the weakened descent enhances the TC genesis in the poleward latitudes. We further estimate the poleward shift of TC genesis to emerge at the 2 K global warming over the Arabian Sea, South Atlantic and Pacific Oceans and at the 4 K warming over the North Pacific. The present results underscore the potential for increasing social and economic risks associated with TCs at higher latitudes.

Background A healthy lifestyle is an important factor for preventing heart failure. However, the association between outdoor light exposure time and heart failure is still unknown. The aim of this study was to examine the association between outdoor light exposure time and the incidence of heart failure. Methods and Results This cohort study included participants from the UK Biobank recruited from 2006 to 2010 who were 40 to 70 years of age and free of heart failure at baseline. The mean follow‐up time was 12.61 years. The outdoor light exposure time was self‐reported at baseline. A restricted cubic spline was performed to examine the potential nonlinear relationship between outdoor light exposure and the incidence of heart failure. Cox proportional hazard models were used to estimate the hazard ratios (HRs) and 95% CIs. During a mean follow‐up of 12.61 years, 13 789 participants were first diagnosed with heart failure. There was a nonlinear (J‐shaped) trend between outdoor light time and heart failure risk. Cox proportional hazard regression models showed that, compared with participants who received an average of 1.0 to 2.5 hours of outdoor light per day, those with 2.5 hours had a higher risk of heart failure after the model was adjusted for age and sex (2.5 hours: HR, 1.11 [95% CI, 1.07–1.15]). These associations were still significant in the fully adjusted models (2.5 hours: HR, 1.07 [95% CI, 1.03–1.11]). Conclusions We found a J‐shaped association between outdoor light exposure time and the risk of incident heart failure, suggesting that moderate exposure to outdoor light may be a prevention strategy for heart failure.

Abstract Circulating tumor cells (CTCs) and tumor‐derived exosomes (TDEs) play an irreplaceable role in the metastatic cascade and preventing them from reaching distant organs via blood circulation helps to reduce the probability of cancer recurrence and metastasis. However, technologies that can simultaneously prevent CTCs and TDEs from reaching distant organs have not been thoroughly developed until now. Here, inspired by hemoperfusion, a pro‐metastatic derivative eliminator (PMDE) is developed for the removal of both CTCs and TDEs from the peripheral blood, which also inhibits their biodistribution in distant organs. This device is designed with a dual antibody‐modified immunosorbent filled into a capture column that draws peripheral blood out of the body to flow through the column to specifically capture CTCs and TDEs, followed by retransfusing the purified blood into the body. The PMDE can efficiently remove CTCs and TDEs from the peripheral blood and has excellent biocompatibility. Interestingly, the PMDE device can significantly inhibit the biodistribution of CTCs and TDEs in the lung and liver by scavenging them. This work provides a new perspective on anti‐metastatic therapy and has broad prospects in clinical applications to prevent metastasis and recurrence.

Abstract Objectives The time for posttreatment tumor progression differs between nasopharyngeal carcinoma (NPC) patients. Herein, we established effective nomograms for predicting early tumor progression (ETP) and late tumor progression (LTP) in NPC patients. Methods We retrospectively enrolled 8292 NPC patients (training cohort: n = 6219; validation cohort: n = 2073). The ELP and LTP were defined as the time to tumor progression ≤24 and >24 months after treatment, respectively. Results The ETP and LTP accounted for 52.6 and 47.4% of the total patient cohort, respectively. Patients who developed ETP had markedly worse overall survival (OS) versus patients who suffered from LTP (5‐year OS: 26.2% vs. 59.7%, p

Abstract With the rapid development of sensor technology and artificial intelligence, the video gesture recognition technology under the background of big data makes human‐computer interaction more natural and flexible, bringing richer interactive experience to teaching, on‐board control, electronic games, etc. In order to perform robust recognition under the conditions of illumination change, background clutter, rapid movement, partial occlusion, an algorithm based on multi‐level feature fusion of two‐stream convolutional neural network is proposed, which includes three main steps. Firstly, the Kinect sensor obtains RGB‐D images to establish a gesture database. At the same time, data enhancement is performed on training and test sets. Then, a model of multi‐level feature fusion of two‐stream convolutional neural network is established and trained. Experiments result show that the proposed network model can robustly track and recognize gestures, and compared with the single‐channel model, the average detection accuracy is improved by 1.08%, and mean average precision (mAP) is improved by 3.56%. The average recognition rate of gestures under occlusion and different light intensity was 93.98%. Finally, in the ASL dataset, LaRED dataset, and 1‐miohand dataset, recognition accuracy shows satisfactory performances compared to the other method.

Abstract Objectives Optimal cutoff thresholds are selected to separate ‘positive’ from ‘negative’ screening results. We evaluated how depression screening tool studies select optimal cutoffs. Methods We included studies from previously conducted meta‐analyses of Patient Health Questionnaire‐9, Edinburgh Postnatal Depression Scale, or Hospital Anxiety and Depression Scale—Depression accuracy. Outcomes included whether an optimal cutoff was selected, method used, recommendations made, and reporting guideline and protocol citation. Results Of 212 included studies, 172 (81%) attempted to identify an optimal cutoff, and 147 of these 172 (85%) reported one or more methods. Methods were heterogeneous with Youden's J (N = 35, 23%) most common. Only 23 of 147 (16%) studies described a rationale for their method. Rationales focused on balancing sensitivity and specificity without describing why desirable. 131 of 172 studies (76%) identified an optimal cutoff other than the standard; most did not make use recommendations (N = 56; 43%) or recommended using a non‐standard cutoff (N = 53; 40%). Only 4 studies cited a reporting guideline, and 4 described a protocol with optimal cutoff selection methods, but none used the protocol method in the published study. Conclusions Research is needed to guide how selection of cutoffs for depression screening tools can be standardized and reflect clinical considerations.

Abstract MRI and CT images have been routinely used in clinical practice for treatment planning of the head‐and‐neck (HAN) radiotherapy. Delineating organs‐at‐risk (OAR) is an essential step in radiotherapy, however, it is time‐consuming and prone to inter‐observer variation. The existing automatic segmentation approaches are either limited by image registration or lack of global spatial awareness, thus under‐performed when dealing with segmentation of complex anatomies. Herein, we propose a full‐scale attention network (FSANet) that integrates bi‐side skip connections, full‐scale feature fusion modules (FFM), a feature pyramid fusion and supervision module (FPFSM) to accurately and efficiently delineate OARs in HAN region on CT and MRI scans. Specifically, bi‐side skip connections were adopted to keep small targets in the deep network and to capture semantic features at different scales. The FFM with cascaded attention mechanisms were used to recalibrate the significant channels and salient regions in the feature maps. The FPFSM was used to guide the network to learn the hierarchical representation so as to improve the segmentation robustness. The proposed algorithm was validated on the public benchmark HAN CT dataset and an in‐house MR dataset. Both results show significant improvement compared to state‐of‐the‐art OAR single‐stage segmentation methods for the HAN region.

Abstract Background Limited studies have explored the association between visceral adipose tissue (VAT) mass and fat‐to‐muscle mass ratio (FMR) and mortality. We aimed to evaluate the sex‐specific association of VAT and FMR with all‐cause and cause‐specific mortality by age. Methods A total of 438 896 participants (49.8% men, mean age ± standard deviation: 57 ± 8 years for men; 56 ± 8 years for women) were included from the UK Biobank cohort. The nature of VAT was predictive, as obtained by sex‐stratified, non‐linear prediction models. Fat and muscle mass were estimated using a bioelectrical impedance assessment device. FMR was calculated as the fat mass divided by the muscle mass in the whole body. VAT and FMRs were divided into quintiles in ascending order, and the 3rd quintile was used as the reference. Cox regression analyses were used to estimate the associations between VAT, FMR and mortality. Results During a median of 12.4 years of follow‐up, we documented 29 903 deaths. After adjusting for various covariates, the individuals in the highest quintiles of VAT and FMR had the highest hazard ratios (HRs) of all‐cause mortality [1.24 (95% confidence interval: 1.17–1.33) for VAT and 1.24 (1.17–1.31) for FMR in men; and 1.11 (1.03–1.21) for VAT in women], except that the 1st quintile of FMR in women had the greatest HR [1.18 (1.09–1.27)]. Significant interactions were observed in both sexes according to age category (P for interaction

Abstract Electrocatalytic N2 reduction reaction (NRR), as an efficient and low‐carbon NH3 production method, is highly desired to replace the traditional Haber–Bosch process under ambient conditions. Nevertheless, its industrial application remains hampered by the low Faradaic efficiency (FE) and an inferior ammonia yield mainly owing to the sluggish kinetics and the competing hydrogen evolution reaction (HER). Here, highly dispersed Fe immobilized in Ti3C2Tx MXene (HD‐Fe‐MXene) is for the first time developed by a controlled etching strategy to act as an efficient electrochemical ammonia production catalyst. In this process, the Al phase of MAX is firstly replaced by Fe through Lewis‐acidic‐melt selective etching, then the HD‐Fe‐MXene is obtained by etching with an HCl solution. The as‐prepared HD‐Fe‐MXene delivers outstanding NRR activity with an FE of 21.8% at −0.1 V versus reversible hydrogen electrode (RHE) and a favorable NH3 yield of 18.25 µg h−1 mg−1 (−0.25 V vs. RHE) in 0.1 M Na2SO4 electrolyte. Notably, HD‐Fe‐MXene exhibits superior stability during the six times recycling tests and the 24 h chronoamperometric test. This excellent NRR electrocatalytic activity is mainly ascribed to the highly dispersed Fe immobilized in the fluorine‐free Ti3C2Tx MXene, which inhibits Fe centers from aggregation for providing abundant active sites for NRR. Moreover, the two‐dimensional structure and the fluorine‐free property of Ti3C2Tx MXene benefit to provide abundant sites for N2 adsorption and promote the electron transfer thus boosting the NRR process. This study delivers a feasible strategy for adding transition metal into the MXene phase to enhance the electrocatalytic activity of MXene‐based catalysts for nitrogen electroreduction to ammonia.

Abstract The oral bacteriome, gut bacteriome, and gut mycobiome are associated with coronavirus disease 2019 (COVID‐19). However, the oral fungal microbiota in COVID‐19 remains unclear. This article aims to characterize the oral mycobiome in COVID‐19 and recovered patients. Tongue coating specimens of 71 COVID‐19 patients, 36 suspected cases (SCs), 22 recovered COVID‐19 patients, 36 SCs who recovered, and 132 controls from Henan are collected and analyzed using internal transcribed spacer sequencing. The richness of oral fungi is increased in COVID‐19 versus controls, and beta diversity analysis reveals separate fungal communities for COVID‐19 and control. The ratio of Ascomycota and Basidiomycota is higher in COVID‐19, and the opportunistic pathogens, including the genera Candida, Saccharomyces, and Simplicillium, are increased in COVID‐19. The classifier based on two fungal biomarkers is constructed and can distinguish COVID‐19 patients from controls in the training, testing, and independent cohorts. Importantly, the classifier successfully diagnoses SCs with positive specific severe acute respiratory syndrome coronavirus 2 immunoglobulin G antibodies as COVID‐19 patients. The correlation between distinct fungi and bacteria in COVID‐19 and control groups is depicted. These data suggest that the oral mycobiome may play a role in COVID‐19.

Abstract To develop a simple and general method for improving the circularly polarized luminescence (CPL) performances of materials is of great significance. In this work, two pairs of CPL‐active homochiral metal–organic frameworks (MOFs) P/M‐Et and P/M‐Et(Cd) with eta topology are reported. In comparison to the reported isomorphic Zn‐imidazolate MOFs P‐Me and M‐Me, both luminescence dissymmetry factor (glum) and photoluminescence quantum yields (ΦPL) of P‐Et and M‐Et are largely improved by simply changing the methyl group to an ethyl group of ligands in P‐Et and M‐Et. Furthermore, the |glum| values are significantly amplified up to 0.015 from 0.0057 by introducing the non‐luminescent halogenated aromatics, while an enhanced fluorescence efficiency is observed simultaneously (from 27.2% to 47.3%). The figure of merit value is about 40 times larger than that of P‐Me and M‐Me. Similarly, the CPL performances of P/M‐Et(Cd) are improved by about five times after encapsulating fluorobenzene molecules. This work represents a new and simple method for developing CPL‐active MOF materials.

Background Autonomic dysfunction has been revealed in patients with acute ischemic stroke and is associated with poor prognosis. However, autonomic nervous system function assessed by heart rate variability (HRV) and its relationship with clinical outcomes in patients undergoing intravenous thrombolysis (IVT) remain unknown. Methods and Results Patients who did and did not undergo IVT between September 2016 and August 2021 were prospectively and consecutively recruited. HRV values were measured at 1 to 3 and 7 to 10 days after stroke to assess autonomic nervous system function. A modified Rankin scale score ≥2 at 90 days was defined as an unfavorable outcome. Finally, the analysis included 466 patients; 224 underwent IVT (48.1%), and 242 did not (51.9%). Linear regression showed a positive correlation of IVT with parasympathetic activation‐related HRV parameters at 1 to 3 days (high frequency: β=0.213, P=0.002) and with both sympathetic (low frequency: β=0.152, P=0.015) and parasympathetic activation‐related HRV parameters (high frequency: β=0.153, P=0.036) at 7 to 10 days after stroke. Logistic regression showed HRV values and autonomic function within 1 to 3 and 7 to 10 days after stroke were independently associated with 3‐month unfavorable outcomes after adjusting for confounders in patients who underwent IVT (all P

Abstract Background The fat‐to‐muscle mass ratio (FMR) might be an indicator to assess type 2 diabetes risk independent of general obesity. However, no longitudinal studies have explored the extent to which total and regional FMRs may confer risks. We aimed to measure the sex‐specific associations between FMRs of the arm, leg, trunk and whole body and incident type 2 diabetes. Methods A total of 464 817 participants (207 286 men and 257 531 women, mean age 56.5 ± 8.2 and 56.2 ± 8.0 years old, respectively) free of diabetes at baseline were included in this prospective cohort study with UK Biobank data. Fat mass and muscle mass were estimated using a bioelectrical impedance assessment device (Tanita BC 418MA). FMR was calculated as fat mass divided by muscle mass in corresponding body parts (total body, arm, leg and trunk). Cox proportional hazard models were used to estimate the aforementioned associations among men and women. Interaction analyses were performed between FMRs and body mass index (BMI) categories (BMI

Abstract Metagenomic evidence of great genetic diversity within the nonconserved regions of the human gut microbial genomes appeals for new methods to elucidate the species‐level variability at high resolution. However, current approaches cannot satisfy this methodologically challenge. In this study, we proposed an efficient binning‐first‐and‐assembly‐later strategy, named MetaTrass, to recover high‐quality species‐resolved genomes based on public reference genomes and the single‐tube long fragment read (stLFR) technology, which enables cobarcoding. MetaTrass can generate genomes with longer contiguity, higher completeness, and lower contamination than those produced by conventional assembly‐first‐and‐binning‐later strategies. From a simulation study on a mock microbial community, MetaTrass showed the potential to improve the contiguity of assembly from kb to Mb without accuracy loss, as compared to other methods based on the next‐generation sequencing technology. From four human fecal samples, MetaTrass successfully retrieved 178 high‐quality genomes, whereas only 58 ones were provided by the optimal performance of other conventional strategies. Most importantly, these high‐quality genomes confirmed the high level of genetic diversity among different samples and unveiled much more. MetaTrass was designed to work with metagenomic reads sequenced by stLFR technology, but is also applicable to other types of cobarcoding libraries. With the high capability of assembling high‐quality genomes of metagenomic data sets, MetaTrass seeks to facilitate the study of spatial characters and dynamics of complex microbial communities at enhanced resolution. The open‐source code of MetaTrass is available at https://github.com/BGI-Qingdao/MetaTrass.

Abstract In this article, a single‐stage bridgeless LLC resonant converter with a constant frequency control method is proposed for a high‐brightness light‐emitting diode (LED) driver. LED strings require drivers with high power density and high efficiency. This article presents a novel LED driver circuit topology based on switch integration and the switching controlled capacitor (SCC) technique. By combining the merits of a totem‐pole bridgeless boost PFC unit and a high frequency SCC‐LLC half‐bridge resonant converter, the proposed topology can achieve high efficiency. Due to the SCC‐LLC circuit topology structure, constant frequency control of the LLC resonant converter is achieved by the regulation of the equivalent resonant capacitance. The proposed novel LED driver topology can automatically achieve soft‐switching characteristics and a high power factor. The operating principle of different operation modes and the characteristics of the proposed LED driver are analysed in detail. Finally, to demonstrate the feature of the proposed topology, a 100 W/70 V laboratory prototype is built. The satisfactory experimental results correspond with the theoretical analysis and parameter design.

Abstract Over the past decade, artificial intelligence (AI) has contributed substantially to the resolution of various medical problems, including cancer. Deep learning (DL), a subfield of AI, is characterized by its ability to perform automated feature extraction and has great power in the assimilation and evaluation of large amounts of complicated data. On the basis of a large quantity of medical data and novel computational technologies, AI, especially DL, has been applied in various aspects of oncology research and has the potential to enhance cancer diagnosis and treatment. These applications range from early cancer detection, diagnosis, classification and grading, molecular characterization of tumors, prediction of patient outcomes and treatment responses, personalized treatment, automatic radiotherapy workflows, novel anti‐cancer drug discovery, and clinical trials. In this review, we introduced the general principle of AI, summarized major areas of its application for cancer diagnosis and treatment, and discussed its future directions and remaining challenges. As the adoption of AI in clinical use is increasing, we anticipate the arrival of AI‐powered cancer care.

Abstract Nasopharyngeal carcinoma (NPC) is a malignant epithelial tumor originating in the nasopharynx and has a high incidence in Southeast Asia and North Africa. To develop these comprehensive guidelines for the diagnosis and management of NPC, the Chinese Society of Clinical Oncology (CSCO) arranged a multi‐disciplinary team comprising of experts from all sub‐specialties of NPC to write, discuss, and revise the guidelines. Based on the findings of evidence‐based medicine in China and abroad, domestic experts have iteratively developed these guidelines to provide proper management of NPC. Overall, the guidelines describe the screening, clinical and pathological diagnosis, staging and risk assessment, therapies, and follow‐up of NPC, which aim to improve the management of NPC.

Abstract Glioblastoma is the most aggressive and common intracranial malignant tumor, and the prognosis is still poor after various treatments. Based on the poor prognosis of glioma, new drugs that suppress the rapid progression and aggressive growth of glioma are urgently needed. It has been reported that nitidine chloride (NC) can inhibit tumor growth and epithelial‐mesenchymal transition (EMT), and EMT is associated with cancer stem cell properties. The present study aimed to investigate the inhibitory effect of NC on the EMT process and stem cell‐like properties in glioma cells. The results showed that the migration and invasion abilities in U87 and LN18 glioma cells were significantly increased after the induction of EMT and these effects were inhibited by NC in a concentration‐dependent manner. NC treatment decreased the expression of EMT markers in glioma cells and self‐renewal capacity of glioma stem‐like cells. We demonstrated that these effects of NC were achieved via JAK2/STAT3 signaling. Taken together, these results indicate that NC inhibits the EMT process and glioma stem‐like properties via JAK2/STAT3 signaling pathway, suggesting that NC may be a potential anti‐glioma drug.

Abstract In this study, we developed a long noncoding RNA (lncRNA)‐based prognostic signature for stratification of patients with head a nd neck squamous cell carcinoma (HNSCC). In total, 493 HNSCC samples obtained from the Cancer Genome Atlas database were divided into training and testing cohorts (3:2 ratio). We identified 3913 immune‐related lncRNAs in the HNSCC training cohort by Pearson correlation analysis; only seven were independently associated with overall survival and were used to develop an immune‐related lncRNA prognostic signature (IRLPS) grouping of HNSCC patients into high‐ and low‐IRLPS subgroups. Univariate and multivariate Cox analyses revealed that low‐IRLPS patients had a better prognosis in all the cohorts, which was retained after stratification by sex, grade, and HPV status. Although the TNM stage was also an independent prognostic factor, the IRLPS had a better discriminability with higher AUC at the 3‐ and 5‐year follow‐ups in all cohorts. Low‐IRLPS samples had more immune cell infiltration and were enriched in immune‐related pathways, while high‐ IRLPS samples were enriched in metabolic pathways. A nomogram constructed including age, TNM stage, and IRLPS showed good calibration. Thus, IRLPS improves the prognostic prediction and also distinguishes different tumor microenvironment (TME) in HNSCC patients.

Abstract Background Oral cavity (OC), oropharyngeal (OP), hypopharyngeal (HP), and laryngeal (LA) squamous cell carcinoma (SCC) have a high incidence of regional lymph node metastasis (LNM). Elective irradiation for clinically node‐negative neck is routinely administered to treat lymph nodes harboring occult metastasis. However, the optimal elective irradiation schemes are still inconclusive. In this study, we aimed to establish individualized elective irradiation schemes for the ipsilateral and contralateral node‐negative neck of these four types of cancer. Methods From July 2005 to December 2018, 793 patients with OC‐SCC, 464 with OP‐SCC, 413 with HP‐SCC, and 645 with LA‐SCC were recruited retrospectively. Based on the actual incidence of LNM and the tumor characteristics, risk factors for contralateral LNM, as well as node level coverage schemes for elective irradiation, were determined using logistic regression analysis. Additionally, we developed a publicly available online tool to facilitate the widespread clinical use of these schemes. Results For the ipsilateral node‐negative neck, elective irradiation at levels I‐III for OC‐SCC and levels II‐IVa for OP‐, HP‐ and LA‐SCC are generally recommended. In addition, level VIIa should be included in patients with OP‐SCC. Multivariate analyses revealed that posterior hypopharyngeal wall and post‐cricoid region involvement were independently associated with level VIIa metastasis in HP‐SCC (all P < 0.05). For the contralateral node‐negative neck, multivariate analyses revealed that ipsilateral N2b2‐N3, tumors with body midline involvement, and degree of tumor invasion were the independent factors for contralateral LNM (all P < 0.05). In patients who require contralateral neck irradiation, levels I‐II are recommended for OC‐SCC, and additional level III is recommended for patients with ipsilateral N3 disease. Levels II‐III are recommended for OP‐, HP‐, and LA‐SCC, and additional level IVa is recommended for patients with advanced T or ipsilateral N classifications. Furthermore, additional level VIIa is recommended only for OP‐SCC with T4 and ipsilateral N3 disease. Conclusion Based on our findings, we suggest that individualized and computer‐aided elective irradiation schemes could reduce irradiation volumes in OC‐, OP‐ and HP‐SCC patients, as compared to current guidelines, and could thus positively impact the patients' quality of life after radiotherapy.

Abstract Transient simulation model of doubly‐fed induction generator‐based wind turbine has a complex model structure and considerable control parameters. An accurate simulation model is especially important for studying the static and transient characteristics of doubly‐fed induction generator‐based wind turbine and the grid‐connected system. Based on the measured data of low voltage ride‐through testing, the integrated parameter identification method is proposed here. Combined with the time‐domain simulation analysis, curve fitting is used to determine the control strategy of doubly‐fed induction generator‐based wind turbine. The improved genetic algorithm is used to identify the generator parameters, power control parameters, and resistance of Crowbar of doubly‐fed induction generator‐based wind turbine. Combined with the electrical parameters provided by the wind turbine manufacturer, electromagnetic transient model on full operation condition and rapid starting period, corresponding to a measured doubly‐fed induction generator‐based wind turbine in West Inner Mongolia Power Grid, is then established, which can operate in the full wind speed range and quickly enter the stable state within 1 s after start‐up. Comparison of simulation results and measured data shows that the established electromagnetic transient simulation model using parameters identified by the proposed method can accurately reflect the key characteristics of doubly‐fed induction generator‐based wind turbine.

With the rapid development of sensor technology and artificial intelligence, the video gesture recognition technology under the background of big data makes human–computer interaction more natural and flexible, bringing the richer interactive experience to teaching, on‐board control, electronic games etc. To perform robust recognition under the conditions of illumination change, background clutter, rapid movement, and partial occlusion, an algorithm based on multi‐level feature fusion of two‐stream convolutional neural network is proposed, which includes three main steps. Firstly, the Kinect sensor obtains red–green–blue‐depth (RGB‐D) images to establish a gesture database. At the same time, data enhancement is performed on the training set and test set. Then, a model of multi‐level feature fusion of a two‐stream convolutional neural network is established and trained. Experiments show that the proposed network model can robustly track and recognise gestures under complex backgrounds (such as similar complexion, illumination changes, and occlusion), and compared with the single‐channel model, the average detection accuracy is improved by 1.08%, and mean average precision is improved by 3.56%.

Abstract Objectives To investigate the prognostic value of magnetic resonance imaging (MRI)‐determined cervical lymph node (CLN) size in nasopharyngeal carcinoma (NPC). Methods We retrospectively reviewed 2066 patients with NPC treated with intensity‐modulated radiotherapy, and randomly divided them into two groups, in a 1:1 ratio. One group was used for training (the training group), and the other one was for internal validation (the validation group). All patients had undergone MRI examination and the maximal axial diameters (MAD) of the axial plane of all positive nodes had been measured and recorded. Results Of 683 patients with CLN metastases in the training group (n = 1033), MAD = 4 cm was associated with worse OS (64.7% vs 84.6%, P

Autophagy and phagocytosis are two important processes that capture and digest materials found in cellular interiors and exteriors, respectively. Aged red blood cells (RBCs) are cleared by phagocytes in vivo. We focused on determining whether autophagy occurs after phagocytes swallow sunset erythrocytes, and whether the degree of autophagy is related to scavenging ability of phagocytes to erythrocytes. In addition, the ability of NLR family pyrin domain containing protein 3 (NLRP3) inflammasome to regulate erythrocyte clearance by phagocytes and its association with autophagy-related protein 16-like protein 1 (ATG16L1) are confirmed. We constructed a stable and low-NLRP3 expression THP-1 cell line using CRISPR/Cas9 technology. The analysis of erythrocyte clearance and autophagy of THP-1 cells with low NLRP3 expression showed that autophagy changes together when THP-1 engulfs aged RBCs. The occurrence of autophagy was dominated by microtubule-associated protein 1A/1B-light chain 3- (LC3-) associated phagocytosis accompanied by canonical autophagy. A negative correlation exists between the clearance of RBCs by THP-1 cells and the degree of autophagy. Downregulating the expression of NLRP3 in THP-1 cells can simultaneously inhibit the scavenging ability of THP-1 to erythrocytes and the degree of autophagy. In addition, the autophagy inhibitor bafilomycin A1 (BafA1) can enhance the phagocytosis ability of THP-1 to erythrocytes and promote the NLRP3 activation in THP-1 cells, while the autophagy inducer rapamycin inhibits the phagocytosis ability of THP-1 to RBCs and downregulates the NLRP3 activation. Results showed that autophagy and phagocytosis may be dynamic balance processes that can provide sufficient nutrition and energy to cells. Choosing NLRP3 as a target may regulate the phagocytic ability and the degree of autophagy in the meantime. These findings may be a potential strategy for regulating the clearance rate of phagocytes to aged RBCs and the secretion of proinflammatory cytokines to ensure transfusion safety.

Abstract Understanding the link between future changes in East Asian summer monsoon (EASM) and global warming levels is of great importance for regional climate change adaptation and mitigation in East Asia. Here, we analyze the projected changes in EASM circulation and precipitation under different warming levels from 1.5 to 5 °C above the preindustrial global mean temperature, using large‐ensemble simulations conducted with Canadian Earth System Model version 2. We find that the model projects enhanced monsoon circulation and precipitation with global warming. The 850‐hPa meridional winds, precipitation, and 500‐hPa vertical ascending motion will be enhanced nonlinearly, while the total column precipitable water will increase quasi‐linearly. The increase in precipitable water in the wet EASM region is only slightly greater than global average but the increase in precipitation is much greater than global one, with enhanced 500‐hPa vertical ascending motion contrary to global mean. The increased low‐level land‐sea thermal contrast leads to the enhanced EASM meridional circulation and thus bring a large amount of moisture into Eastern China, providing favorable conditions for additional increase in precipitation. A simplified moisture budget analysis shows that the dynamic component related to strengthening monsoon circulation plays dominant role in the increase in EASM precipitation when the global temperature increases by more than approximately 2 °C, while the thermodynamic component caused by increased water vapor is important when the warming is smaller.

Abstract Respiratory tract microbiome is closely related to respiratory tract infections, while characterization of oropharyngeal microbiome in recovered coronavirus disease 2019 (COVID‐19) patients is not studied. Herein, oropharyngeal swabs are collected from confirmed cases (CCs) with COVID‐19 (73 subjects), suspected cases (SCs) (36), confirmed cases who recovered (21), suspected cases who recovered (36), and healthy controls (Hs) (140) and then completed MiSeq sequencing. Oropharyngeal microbial α‐diversity is markedly reduced in CCs versus Hs. Opportunistic pathogens are increased, while butyrate‐producing genera are decreased in CCs versus Hs. The classifier based on eight optimal microbial markers is constructed through a random forest model and reached great diagnostic efficacy in both discovery and validation cohorts. Notably, the classifier successfully diagnosed SCs with positive IgG antibody as CCs and is demonstrated from the perspective of the microbiome. Importantly, several genera with significant differences gradually increase and decrease along with recovery from COVID‐19. Forty‐four oropharyngeal operational taxonomy units (OTUs) are closely correlated with 11 clinical indicators of SARS‐CoV‐2 infection and Hs based on Spearman correlation analysis. Together, this research is the first to characterize oropharyngeal microbiota in recovered COVID‐19 cases and suspected cases, to successfully construct and validate the diagnostic model for COVID‐19 and to depict the correlations between microbial OTUs and clinical indicators.

Abstract Based on the observational dataset SA‐OBS and model outputs from the Community Earth System Model Large Ensemble project, this study investigates heatwaves in Southeast Asia in the current and future warmer climate. A heatwave is detected when the daily maximum temperature exceeds the 90th percentile threshold at each grid for at least three consecutive days. Three characteristics describing the frequency, duration, and amplitude of heatwaves are examined, including the sum of heatwave days per year (HWF) satisfying the heatwave definition, the length of the longest yearly heatwave event (HWD), and the hottest amplitude of the hottest yearly heatwave event (HWA). Results indicate that increased global warming is associated with substantial changes in heatwave characteristics over Southeast Asia, with more frequent heatwaves, longer heatwave duration, and higher extreme temperatures. The increase in HWA has a linear growth against global warming levels with distinct regional differences between the Maritime Continent and the Indochina Peninsula due to their different heat content of lower atmospheric boundaries. In contrast, those in HWF and HWD have nonlinear growth characteristics. The projected warmer future tends to be associated with a higher risk ratio value with the occurrence of rarer extreme heatwaves relative to the current climate. These results reiterate the potential risks of extreme regional heatwaves if global warming is unrestricted.

Abstract Background To identify thyroid dose‐volume thresholds for radiotherapy (RT)‐related hypothyroidism (HT) in patients with nasopharyngeal carcinoma (NPC) treated with intensity‐modulated RT (IMRT). In this way, we desired to guide the design of treatment plans and, finally, lower HT prevalence. Methods In total, 345 NPC patients treated with IMRT were evaluated retrospectively during a median follow‐up of 45.2 (range, 11.3‐64.9) months. Serum‐based assessments of thyroid function before and after IMRT were monitored periodically. Thyroid dose‐volume parameters were analyzed for their association with HT risk. Results In total, 44.1% of patients (152/345) developed primary HT. Analyses of thyroid dose‐volume parameters identified a stringent dose‐volume histogram (DVH) threshold defined by V25Gy (the percentage thyroid volume that receives >25 Gy, not the absolute volume) ≤60%, V35Gy ≤ 55%, and V45Gy ≤ 45%. Patients whose thyroid DVHs satisfied these constraints had a lower prevalence of 2‐year HT compared with the overall prevalence (13.2% vs 25.8%, P 95%, V35Gy > 90%, and V45Gy > 75%, and patients whose thyroid DVHs satisfied with these constraints had a higher prevalence of 2‐year HT than the overall incidence (36.0% vs 25.8%, P 95%, V35Gy > 90%, and V45Gy > 75% as the “inhibition” DVH line, under the precondition of not compromising the target coverage. These findings could help in the design of individual treatment plans and, eventually, to lowering of HT prevalence.

Abstract The standard of care for patients with locoregionally advanced nasopharyngeal carcinoma is concurrent platinum-based chemoradiotherapy. Existing literature have demonstrated that the addition of gemcitabine and cisplatin as induction chemotherapy in locoregionally advanced nasopharyngeal carcinoma may have promising efficacy but were from phase 2 clinical trials. Stronger evidence-based data in forms of phase 3 clinical trial investigating the survival benefits of adding gemcitabine and cisplatin induction chemotherapy for such patients have been urgently warranted. In one of our recent studies published in the New England Journal of Medicine, “Gemcitabine and cisplatin induction chemotherapy in nasopharyngeal carcinoma”, 480 locoregionally advanced nasopharyngeal carcinoma patients from 12 hospitals across China were randomly assigned in a 1:1 ratio to receive either chemoradiotherapy alone or gemcitabine plus cisplatin and chemoradiotherapy. Our findings evinced that, as compared to chemoradiotherapy alone, the addition of induction chemotherapy comprising of gemcitabine plus cisplatin to concurrent cisplatin-radiotherapy to patients with locoregionally advanced nasopharyngeal carcinoma was safe, demonstrated improved recurrence-free survival, overall survival, and distant recurrence-free survival, and marginally superior locoregional recurrence-free survival.

Abstract Background Intensity‐modulated radiotherapy (IMRT) provides excellent local control in nasopharyngeal carcinoma (NPC). We investigated whether simplifying 8th American Joint Committee on Cancer staging system T categories improves prognostic value. Methods We used 2191 NPC patients as a training set and 414 patients separately as an independent, external validation cohort. Results In the training set, local relapse‐free survival (LRFS), disease‐free survival (DFS), and overall survival (OS) were not significantly different between the 8th edition T2/T3 (P = 0.610, 0.380 and 0.353, respectively). Merging T2 and T3 to proposed T2 (proT2) provided significant differences in LRFS, DFS, and OS between proposed T categories. Proposed T categories had similar c‐indices for LRFS, DFS, and OS (vs the 8th edition), which was validated in the external cohorts. Moreover, for DFS, the adjusted HRs of the proT2N0 (3.8), proT1N1 (3.8), and proT2N1 (6.0) subsets were similar; the adjusted HRs of the proT3N0 (7.0), proT3N1 (11.4), proT1N2 (11.0), proT2N2 (11.6), and proT3N2 (13.3) subsets were similar; the adjusted HRs of the proT1N3 (17.8), proT2N3 (15.3), and proT3N3 (26.4) subsets were similar; the results of the adjusted HRs for OS had the same rule. Defining proT1N0 as stage I; proT1N1/proT2N0‐1 as stage II; proT3N0‐2/proT1‐2N2 as stage III; and proT1‐3N3 as stage IVa generated orderly, significant differences in DFS and OS between stages in the training set and external validation cohort. Conclusions In the IMRT era, three T categories are more reasonable (merging T2/T3 into T2) and proT3N0‐2 (the 8th edition T4N0‐2) should be down‐staged to stage III.

Background Our previous study showed that SUMO1 expression is closely related to progression in non‐small cell lung cancer (NSCLC); however, the function of SUMO1 in NSCLC has not yet been well elucidated. Methods SUMO1 was enhanced or silenced in two NSCLC cell lines by using either forced SUMO1 expression or short hairpin RNA against SUMO1 lentiviral vectors, respectively. The biological functions of SUMO1 in NSCLC were investigated through colony‐formation, cell proliferation, and invasion assays, and cell cycle analysis. NF‐κB expression was detected in the overexpressed and silenced SUMO1 cell lines. Immunohistochemistry was used to detect an association between SUMO1 and NF‐κB in the cancer and adjacent tissues of 168 patients with lung cancer. Results Overexpressed SUMO1 promoted the proliferation rate, colony formation ability, invasion, and NF‐κB expression in an A549 cell line. Conversely, SUMO1 depletion inhibited the cell growth rate, colony formation ability, invasion, and NF‐κB expression in a Calu‐1 cell line. SUMO1 expression was significantly correlated with NF‐κB expression in lung adenocarcinoma and squamous carcinoma patients (r > 0.5, P