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Abstract Acute hydrocephalus is a severe complication that may occur early after an intracerebral hemorrhage (ICH). However, clinical factors predicting the occurrence of acute hydrocephalus have rarely been studied. This study aimed to establish a nomogram model to predict early acute hydrocephalus after ICH. We retrospectively analyzed the data of 930 patients with ICH who were treated at our hospital between January 2017 and May 2024. Least absolute shrinkage and selection operator (LASSO) regression analysis was used to screen for risk factors for acute hydrocephalus, and stepwise logistic regression analysis was used to construct the prediction model, which was visualized using a nomogram. Data were randomly divided into training (n = 652) and test (n = 278) sets at a 7:3 ratio. A total of 930 patients were included, of whom 123 (13.2%) developed acute hydrocephalus within 6 h of being diagnosed with ICH. Univariate analysis revealed that 11 indicators were associated with acute hydrocephalus. In the training set, LASSO and stepwise logistic regression analyses identified four independent risk factors that were used to establish a prediction model. These were the modified Graeb score, age, infratentorial hemorrhage > 15 mL, and thalamic hemorrhage > 15 mL. A graphical nomogram was then developed. The area under the receiver operating characteristic (ROC) curve was 0.974 (95% confidence interval 0.961–0.987). In the Hosmer–Lemeshow test, the p-value was 0.887. The mean absolute error of the calibration plot was 0.012. The decision curve analysis (DCA) validated the fitness and clinical application value of this nomogram. Internal validation showed the test set was in good accordance with the training set. The nomogram prediction model showed good accuracy and could be used to predict the risk of early acute hydrocephalus after ICH, thereby aiding neurologist in making rapid clinical decisions.

Abstract Background Cellular senescence can be induced in mammalian tissues by multiple stimuli, including aging, oncogene activation and loss of tumor suppressor genes, and various types of stresses. While senescence is a tumor suppressing mechanism when induced within premalignant or malignant tumor cells, senescent cells can promote cancer development through increased secretion of growth factors, cytokines, chemokines, extracellular matrix, and degradative enzymes, collectively known as senescence-associated secretory phenotype (SASP). Previous studies indicated that senescent cells, through SASP factors, stimulate tumor cell invasion that is a critical step in cancer cell metastasis. Methods In the current study, we investigated the effect of senescent cells on the motility of breast cancer cells, which is another key step in cancer cell metastasis. We analyzed the motility of breast cancer cells co-cultured with senescent cells in vitro and metastasis of the breast cancer cells co-injected with senescent cells in orthotopic xenograft models. We also delineated the signaling pathway mediating the effect of senescent cells on cancer cell motility. Results Our results indicate that senescent cells stimulated the migration of breast cancer cells through secretion of GM-CSF and bFGF, which in turn induced activation of the JNK pathway in cancer cells. More importantly, senescent cells promoted breast cancer metastasis, with a minimum effect on the primary tumor growth, in orthotopic xenograft mouse models. Conclusions These results have revealed an additional mechanism by which senescent cells promote tumor cell metastasis and tumor progression, and will potentially lead to identification of novel targets for cancer therapies that suppress metastasis, the major cause of cancer mortality.

Abstract Background Growth hormone-secreting pituitary neuroendocrine tumors can be pathologically classified into densely granulated (DGGH) and sparsely granulated types (SGGH). SGGH is more aggressive and associated with a poorer prognosis. While epigenetic regulation is vital in tumorigenesis and progression, the role of N6-methyladenosine (m6A) in aggressive behavior has yet to be elucidated. Methods We performed m6A-sequencing on tumor samples from 8 DGGH and 8 SGGH patients, complemented by a suite of assays including ELISA, immuno-histochemistry, -blotting and -fluorescence, qPCR, MeRIP, RIP, and RNA stability experiments, aiming to delineate the influence of m6A on tumor behavior. We further assessed the therapeutic potential of targeted drugs using cell cultures, organoid models, and animal studies. Results We discovered a significant reduction of m6A levels in SGGH compared to DGGH, with an elevated expression of fat mass and obesity-associated protein (FTO), an m6A demethylase, in SGGH subtype. Series of in vivo and in vitro experiments demonstrated that FTO inhibition in tumor cells robustly diminishes hypoxia resistance, attenuates growth hormone secretion, and augments responsiveness to octreotide. Mechanically, FTO-mediated m6A demethylation destabilizes desmoplakin (DSP) mRNA, mediated by the m6A reader FMR1, leading to prohibited desmosome integrity and enhanced tumor hypoxia tolerance. Targeting the FTO-DSP-SSTR2 axis curtailed growth hormone secretion, therefor sensitizing tumors to octreotide therapy. Conclusion Our study reveals the critical role of FTO in the aggressive growth hormone-secreting pituitary neuroendocrine tumors subtype and suggests FTO may represent a new therapeutic target for refractory/persistent SGGH.

Abstract Background Polydactyly is a prevalent congenital anomaly with an incidence of 2.14 per 1000 live births in China. GLI family zinc finger 3 (GLI3) is a classical causative gene of polydactyly, and serves as a pivotal transcription factor in the hedgehog signaling pathway, regulating the development of the anterior-posterior axis in limbs. Methods Three pedigrees of polydactyly patients were enrolled from Hunan Province, China. Pathogenic variants were identified by whole-exome sequencing (WES) and Sanger sequencing. Results Three variants in GLI3 were identified in three unrelated families, including a novel deletion variant (c.1372del, p.Thr458GlnfsTer44), a novel insertion-deletion (indel) variant (c.1967_1968delinsAA, p.Ser656Ter), and a nonsense variant (c.2374 C > T, p.Arg792Ter). These variants were present exclusively in patients but not in healthy individuals. Conclusions We identified three pathogenic GLI3 variants in polydactyly patients, broadening the genetic spectrum of GLI3 and contributing significantly to genetic counseling and diagnosis for polydactyly.

Abstract Background Rickettsia and related diseases have been identified as significant global public health threats. This study involved comprehensive field and systematic investigations of various rickettsial organisms in Yunnan Province. Methods Between May 18, 2011 and November 23, 2020, field investigations were conducted across 42 counties in Yunnan Province, China, encompassing small mammals, livestock, and ticks. Preliminary screenings for Rickettsiales involved amplifying the 16S rRNA genes, along with additional genus- or species-specific genes, which were subsequently confirmed through sequencing results. Sequence comparisons were carried out using the Basic Local Alignment Search Tool (BLAST). Phylogenetic relationships were analyzed using the default parameters in the Molecular Evolutionary Genetics Analysis (MEGA) program. The chi-squared test was used to assess the diversities and component ratios of rickettsial agents across various parameters. Results A total of 7964 samples were collected from small mammals, livestock, and ticks through Yunnan Province and submitted for screening for rickettsial organisms. Sixteen rickettsial species from the genera Rickettsia, Anaplasma, Ehrlichia, Neoehrlichia, and Wolbachia were detected, with an overall prevalence of 14.72%. Among these, 11 species were identified as pathogens or potential pathogens to humans and livestock. Specifically, 10 rickettsial organisms were widely found in 42.11% (24 out of 57) of small mammal species. High prevalence was observed in Dremomys samples at 5.60%, in samples from regions with latitudes above 4000 m or alpine meadows, and in those obtained from Yuanmou County. Anaplasma phagocytophilum and Candidatus Neoehrlichia mikurensis were broadly infecting multiple genera of animal hosts. In contrast, the small mammal genera Neodon, Dremomys, Ochotona, Anourosorex, and Mus were carrying individually specific rickettsial agents, indicating host tropism. There were 13 rickettsial species detected in 57.14% (8 out of 14) of tick species, with the highest prevalence (37.07%) observed in the genus Rhipicephalus. Eight rickettsial species were identified in 2375 livestock samples. Notably, six new Rickettsiales variants/strains were discovered, and Candidatus Rickettsia longicornii was unambiguously identified. Conclusions This large-scale survey provided further insight into the high genetic diversity and overall prevalence of emerging Rickettsiales within endemic hotspots in Yunnan Province. The potential threats posed by these emerging tick-borne Rickettsiales to public health warrant attention, underscoring the need for effective strategies to guide the prevention and control of emerging zoonotic diseases in China. Graphical Abstract

Abstract Chronic kidney disease (CKD) poses a significant global health dilemma, emerging from complex causes. Although our prior research has indicated that a deficiency in Reticulon-3 (RTN3) accelerates renal disease progression, a thorough examination of RTN3 on kidney function and pathology remains underexplored. To address this critical need, we generated Rtn3-null mice to study the consequences of RTN3 protein deficiency on CKD. Single-cell transcriptomic analyses were performed on 47,885 cells from the renal cortex of both healthy and Rtn3-null mice, enabling us to compare spatial architectures and expression profiles across 14 distinct cell types. Our analysis revealed that RTN3 deficiency leads to significant alterations in the spatial organization and gene expression profiles of renal cells, reflecting CKD pathology. Specifically, RTN3 deficiency was associated with Lars2 overexpression, which in turn caused mitochondrial dysfunction and increased reactive oxygen species levels. This shift induced a transition in renal epithelial cells from a functional state to a fibrogenic state, thus promoting renal fibrosis. Additionally, RTN3 deficiency was found to drive the endothelial-to-mesenchymal transition process and disrupt cell-cell communication, further exacerbating renal fibrosis. Immunohistochemistry and Western-Blot techniques were used to validate these observations, reinforcing the critical role of RTN3 in CKD pathogenesis. The deficiency of RTN3 protein in CKD leads to profound changes in cellular architecture and molecular profiles. Our work seeks to elevate the understanding of RTN3’s role in CKD’s narrative and position it as a promising therapeutic contender.

Reuterin, a mixture of different forms of 3-hydroxypropanal (3-HPA), including HPA hydrate and HPA dimer, is an antimicrobial compound converted from glycerol by Lactobacillus reuteri and other strains. Although its antimicrobial function may be related to its interaction with thiol groups, its temperature stability and effect on the gut environment remain unclear. The present study evaluated the antimicrobial effects and activity of reuterin against Escherichia coli and Salmonella typhimurium. Utilization of a reliable in vitro gut microbiome fermentation system revealed that reuterin has a modulatory effect on the gut microbial community. Reuterin treatment completely inhibited H2 and NH3 production in the gut and significantly enhanced the synthesis of branched short-chain fatty acids. 16s rRNA sequencing indicated that reuterin promoted the growth of Proteobacteria and Bacteroidetes in the in vitro system and significantly modulated gut microbiota composition.

Abstract Despite the successful application of immune checkpoint therapy, no response or recurrence is typical in lung cancer. Cancer stem cells (CSCs) have been identified as a crucial player in immunotherapy-related resistance. Ferroptosis, a form of cell death driven by iron-dependent lipid peroxidation, is highly regulated by cellular metabolism remolding and has been shown to have synergistic effects when combined with immunotherapy. Metabolic adaption of CSCs drives tumor resistance, yet the mechanisms of their ferroptosis defense in tumor immune evasion remain elusive. Here, through metabolomics, transcriptomics, a lung epithelial-specific Cpt1a-knockout mouse model, and clinical analysis, we demonstrate that CPT1A, a key rate-limiting enzyme of fatty acid oxidation, acts with L-carnitine, derived from tumor-associated macrophages to drive ferroptosis-resistance and CD8+ T cells inactivation in lung cancer. Mechanistically, CPT1A restrains ubiquitination and degradation of c-Myc, while c-Myc transcriptionally activates CPT1A expression. The CPT1A/c-Myc positive feedback loop further enhances the cellular antioxidant capacity by activating the NRF2/GPX4 system and reduces the amount of phospholipid polyunsaturated fatty acids through ACSL4 downregulating, thereby suppressing ferroptosis in CSCs. Significantly, targeting CPT1A enhances immune checkpoint blockade-induced anti-tumor immunity and tumoral ferroptosis in tumor-bearing mice. The results illustrate the potential of a mechanism-guided therapeutic strategy by targeting a metabolic vulnerability in the ferroptosis of CSCs to improve the efficacy of lung cancer immunotherapy.

Background: Borrelia miyamotoi is a spirochete species transmitted via hard ticks. Following its discovery in Japan, this pathogen has been detected around the world, and is increasingly confirmed as a human pathogen causing febrile disease, namely relapsing fever. Its presence has been confirmed in the Northeast China. However, there is little information regarding the presence of B. miyamotoi and other hard-tick-borne relapsing fever spirochetes in southern China including Yunnan province, where tick and animal species are abundant and many people both inhabit and visit for recreation. Methods: For the present study, we collected samples of ticks, wildlife, and domestic animal hosts from different counties in Yunnan province. Nucleic acids from samples were extracted, and the presence of B. miyamotoi and other relapsing fever spirochetes was confirmed using polymerase chain reaction (PCR) for the 16S rRNA specific target gene fragment. The positive samples were then amplified for partial genome of the flaB and glpQ genes. Statistical differences in its distribution were analyzed by SPSS 20 software. Sequence of partial 16S rRNA, flaB and glpQ genome were analyzed and phylogenetic trees were constructed. Results: A total of 8260 samples including 2304 ticks, 4120 small mammals and 1836 blood of domestic animal hosts were collected for screening for infection of B. miyamotoi and other relapsing fever spirochetes. Cattle and sheep act as the main hosts and Rhipicephalus microplus, Haemaphysalis nepalensis, H. kolonini and Ixodes ovatus were identified as the important vector host with high prevalence or wide distribution. Only one Mus caroli (mouse) and one Sorex alpinus (shrew) were confirmed positive for relapsing fever spirochetes. Evidence of vertical transmission in ticks was also confirmed. Two known strains of B. miyamotoi and one novel relapsing fever spirochetes, B. theileri-like agent, were confirmed and described with their host adaptation, mutation, and potential risk of spreading and spillover for human beings. Conclusions: Our results provide new evidence of relapsing fever spirochetes in vector and animal hosts in Yunnan province based on large sample sizes, and offer guidance on further investigation, surveillance and monitoring of this pathogen.

The traditional underground power cable fault positioning method relies on subjective parameter selection and noise resistance is poor. It cannot meet the accurate fault positioning requirements of underground power cable under strong noise background. In order to solve the above problems, a fault positioning method of underground power cable based on salp swarm algorithm (SSA) optimizing variational mode decomposition (VMD) combined with novel Teager energy operator (NTEO) is proposed. In response to the problem of modal aliasing, over decomposition, and under decomposition in signal decomposition of VMD, SSA is used to optimize the modal number K and penalty factor α of VMD parameters using fuzzy entropy as the fitness function. The intrinsic modal function that better reflects the fault feature information is obtained. NTEO is used to calibrate the first wave head to obtain the arrival time of the wave heads at both ends. The fault position is determined based on the dual end distance measurement method. PSCAD/EMTDC is used for underground power cable fault simulation. It simulates underground fault signals with strong background noise. The results show the following points. ① After adding 9 dB and 12 dB noise to the ideal current signal, the signal-to-noise ratio of SSA-VMD is the lowest, and the Pearson correlation coefficient is the highest. It indicates that SSA-VMD can effectively preserve the characteristic information of the signal while minimizing noise. ② Under different transition resistances, the positioning precision of SSA-VMD-NTEO is relatively high. ③ Under different fault phase angles, although SSA-VMD-NTEO may have different sampling points, the positioning position remains unchanged and still maintains high precision. ④ SSA−VMD-NTEO can ensure high positioning precision at different fault distances. ⑤ Under high underground noise and a sampling frequency of 10 MHz, SSA-VMD-NTEO has significant advantages in positioning precision compared to wavelet modulus maximum and VMD+NTEO methods.

Lithium metal anode (LMA) is a promising candidate for achieving next-generation high-energy-density batteries due to its ultrahigh theoretical capacity and most negative electrochemical potential. However, the practical application of lithium metal battery (LMB) is largely retarded by the instable interfaces, uncontrolled dendrites, and rapid capacity deterioration. Herein, we present a comprehensive overview towards the working principles and inherent challenges of LMAs. Firstly, we diligently summarize the intrinsic mechanism of Li stripping and plating process. The recent advances in atomic and mesoscale simulations which are crucial in guiding mechanism study and material design are also summarized. Furthermore, the advanced engineering strategies which have been proved effective in protecting LMAs are systematically reviewed, including electrolyte optimization, artificial interface, composite/alloy anodes and so on. Finally, we highlight the current limitations and promising research directions of LMAs. This review sheds new lights on deeply understanding the intrinsic mechanism of LMAs, and calls for more endeavors to realize practical Li metal batteries.

Automated packing is urgently needed in apple production. This paper proposes an improved genetic algorithm fused with an optimal parameter selection algorithm to optimize the two-posture manipulator working path of packing robots. First, the structure and working principle of the packing robot were designed. Second, the kinematics and packing paths of the two-posture manipulator were analyzed. Finally, the path optimization method for the two-posture manipulator was introduced. The method was based on the improved genetic algorithm by using a two-level coding and region crossover operator. The parameter values can be automatically determined by the optimal parameter selection algorithm. Ten repeated comparative tests show that the total packing time is 23.86 s under the working conditions of four grasping points and fourteen placing points. The optimal performance of the proposed algorithm is better than that of the traditional genetic algorithm, and the average optimization amplitudes are 14.63%, 15.42%, 16.24%, and 13.82% for 9-groove, 12-groove, 14-groove, and 16-groove trays, respectively. The proposed algorithm can effectively prevent the premature convergence problem of the traditional genetic algorithm and the optimization process instability problem, improve the range of optimization, and reduce the manipulator working time during packing.

IntroductionIn sports competitions, judge scoring data serve as an objective measure of an athlete’s performance level. However, research has indicated the unreliability of objective measurements. Controversy often arises regarding the quality of judge scoring data, undermining fairness and justice in sports competitions.MethodThis paper proposes a method utilizing the Kendall covariance coefficient and the Kendall correlation coefficient for the thorough evaluation of judging data quality in diving events. The analysis is structured around four key elements: overall competition, individual divers, specific rounds, and distinct diving techniques. Each element is analyzed across three dimensions: the collective data quality from the judging panel, interjudge data quality comparisons, and the alignment of individual judges’ scores with the final tallied scores.ResultsTwo case studies serve to illustrate the application of this method. The Kendall covariance coefficient is employed to assess the data quality from the judges as a unified entity, whereas the Kendall correlation coefficient is utilized to evaluate the data quality from individual judges. Results show that the data quality of the judge group’s scoring is high, while the data quality of the judge group’s scoring for the 6th diver, the 5th round, Dive No. 5152B, Judge 5 and 6 in the Competition 1, and the 1st diver, the 3rd round, Dive No. 6245D, Judge 4 in the Competition 2 is inconsistent with the others.DiscussionThis approach uncovers disparities in data quality attributed to the judges’ panel across each diver, each round, and the various diving maneuvers. However, the Kendall correlation coefficient may not be suitable for evaluating data quality when both the data differences and the sample size are small.

Abstract As a group of ectoparasites, chiggers (larvae of chigger mites) are the exclusive vector of scrub typhus (tsutsugamushi disease). Rodents are the most important hosts of chiggers. The Anderson's niviventer rat, Niviventer andersoni, is an endemic species of rodent in China. However, few studies have involved this endemic rodent species and its ectoparasites including chiggers. According to the field investigation in five provincial regions of southwest China between 2001 and 2019, this paper retrospectively analysed the infestation and distribution of chiggers on the body surface of N. andersoni in southwest China for the first time. From 77 Anderson's niviventer rats captured, a total of 527 chiggers were collected and they were identified as 39 species and nine genera in two subfamilies of family Trombiculidae. Of 39 chigger species identified, Leptotrombidium deliense and L. scutellare are the most important vectors of scrub typhus in China. The overall infestation indexes were PM = 29.87%, MA = 6.84 and MI = 22.91, and the indexes of chigger mite community were Mf = 39, H' = 2.60, E = 0.71 and D = 0.12. The dominant chigger species are L. wenense, L. xiaguanense and L. fujianense with a total Cr = 51.04%, among which L. wenense is one of the six main vectors of scrub typhus in China. The dominant chigger species are of aggregated distribution among different individuals of the rats.

The coronavirus disease 2019 (COVID-19) pandemic caused by frequently mutating severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has had a worldwide impact. However, detailed data on the potential aerosol transmission of SARS-CoV-2 in real-world and controlled laboratory settings remain sparse. During the COVID-19 pandemic in Shanghai, China in 2022, samples were collected in a Fangcang shelter hospital, a large-scale temporary hospital rapidly built by converting the existing National Exhibition and Convention Center (Shanghai) into a health care facility. Aerosol samples at different sites and intervals around patients and in public areas, surface samples, and pharyngeal swab samples from corresponding patients were included. Samples were tested for SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR) assays, followed by sequencing if the cycle threshold (Ct) value was < 30. The positivity rate for SARS-CoV-2 in aerosol samples was high in contaminated zones (37.5%, 104/277), especially around the bed (41.2%, 68/165) and near ventilation inlets (45.2%, 14/31). The prevalence of SARS-CoV-2 around the bed, public areas, and air inlets of exhaust vents fluctuated and was closely related to the positivity rate among patients at corresponding sampling sites. Some surface samples of different personal protective equipment from medical staff had high positivity rates. Sixty sequences of joined ORF1ab and spike genes obtained from sixty samples represented two main clusters of Omicron SARS-CoV-2. There was consistency in virus sequences from the same patient and their environment, and the detected virus sequences matched those of virus strains in circulation during the collection periods, which indicated a high likelihood of cross-contamination in the Fangcang shelter hospital. In summary, the results provide a quantitative and real landscape of the aerosol transmission of SARS-CoV-2 and a patient-centered view of contamination in large and enclosed spaces and offer a useful guide for taking targeted measures to avoid nosocomial infections during the management of SARS-CoV-2 or other respiratory virus diseases in a Fangcang shelter hospital.

Abstract Despite the fact that the response of tropical hydroclimate to North Atlantic cooling events during the Heinrich Stadial 1 (HS1) has been extensively studied in African, South American and Indonesia, the nature of such responses remains debated. Here we investigate the tropical hydroclimate pattern over the Indo-Asian-Australian monsoon region during the HS1 by integrating hydroclimatic records, and examining a δ18Oseawater record from Globigerinoides ruber (white) in the tropical Indian Ocean. Our findings indicate that tropical hydrological conditions were synchronously arid in both hemispheres during the early HS1 (~18.3-16.3 ka) in the Indo-Asian-Australian monsoon region, except for a narrow, wet hydrological belt in northern low latitudes, suggesting the existence of a contracted tropical precipitation belt at that time. This study reveals that the meltwater discharge and resulting changes in global temperatures and El Niño exerted a profound influence on the tropical hydroclimate in the Indo-Asian-Australian monsoon region during the early HS1.

Abstract The discovery of the endothelium as a major regulator of vascular tone triggered intense research among basic and clinical investigators to unravel the physiologic and pathophysiologic significance of this phenomenon. Sphingosine‐l‐phosphate (S1P), derived from the vascular endothelium, is a significant regulator of blood pressure. However, the mechanisms underlying the regulation of S1P biosynthetic pathways in arteries remain to be further clarified. Here, we reported that Reticulon 3 (RTN3) regulated endothelial sphingolipid biosynthesis and blood pressure. We employed public datasets, patients, and mouse models to explore the pathophysiological roles of RTN3 in blood pressure control. The underlying mechanisms were studied in human umbilical vein endothelial cells (HUVECs). We reported that increased RTN3 was found in patients and that RTN3‐null mice presented hypotension. In HUVECs, RTN3 can regulate migration and tube formation via the S1P signaling pathway. Mechanistically, RTN3 can interact with CERS2 to promote the selective autophagy of CERS2 and further influence S1P signals to control blood pressure. We also identified an RTN3 variant (c.116C>T, p.T39M) in a family with hypertension. Our data provided the first evidence of the association between RTN3 level changes and blood pressure anomalies and preliminarily elucidated the importance of RTN3 in S1P metabolism and blood pressure regulation.

BackgroundThe worldwide spread of monkeypox (mpox) has witnessed a significant increase, particularly in nonendemic countries. ObjectiveWe aimed to investigate the changing clinical symptoms associated with mpox from 1970 to 2023 and explore their interrelations. MethodsIn this systematic review and meta-analysis, 3 electronic databases were searched for English peer-reviewed studies conducted from January 1970 to April 2023 that reported any symptoms among confirmed mpox cases. We categorized the mpox epidemics into 3 periods: 1970-2002 (period 1, within the African region), 2003-2021(period 2, epidemics outside Africa), and 2022-2023 (period 3, worldwide outbreak). Following PRISMA guidelines, a meta-analysis was performed to estimate the pooled prevalence for each symptom. The correlation among symptoms was analyzed and visualized using network analysis. ResultsThe meta-analysis included 61 studies that reported 21 symptoms in 720 patients from period 1, 39 symptoms in 1756 patients from period 2, and 37 symptoms in 12,277 patients from period 3. The most common symptom among patients from all 3 periods was rash (period 1: 92.6%, 95% CI 78.2%-100%; period 2: 100%, 95% CI 99.9%-100%; and period 3: 94.8%, 95% CI 90.9%-98.8%), followed by lymphadenopathy (period 1: 59.8%, 95% CI 50.3%-69.2%; period 2: 74.1%, 95% CI 64.2%-84.1%; and period 3: 61.1%, 95% CI 54.2%-68.1%). Fever (99%, 95% CI 97%-100%), enlarged lymph nodes (80.5%, 95% CI 75.4%-85.0%), and headache (69.1%, 95% CI 4%-100%) were the main symptoms in period 1, with a significant decrease in period 3: 37.9%, 31.2%, and 28.7%, respectively. Chills/rigors (73.3%, 95% CI 60.9%-85.7%), fatigue (68.2%, 95% CI 51.6%-84.8%), and dysphagia/swallowing difficulty (61.2%, 95% CI 10.5%-100%) emerged as primary new symptoms in period 2 and decreased significantly in period 3. Most other symptoms remained unchanged or decreased in period 3 compared to the former 2 periods. Nausea/vomiting had the highest degree of correlation (with 13 symptoms) and was highly positively correlated with lymphadenopathy (r=0.908) and conjunctivitis (r=0.900) in period 2. In contrast, rash and headache were 2 symptoms with the highest degree of correlation (with 21 and 21 symptoms, respectively) in period 3 and were highly positively correlated with fever (r=0.918 and 0.789, respectively). ConclusionsThe manifestation of symptoms in patients with mpox has become more diverse, leading to an increase in their correlation. Although the prevalence of rash remains steady, other symptoms have decreased. It is necessary to surveil the evolving nature of mpox and the consequential changes in clinical characteristics. Epidemic countries may shift their focus on the potential association among symptoms and the high synergy risk. Trial RegistrationPROSPERO Registration: CRD42023403282; http://tinyurl.com/yruuas5n

【Objective】China is a large country of pork production and consumption in the world, but most fresh meat is sold extensively while little of them is sold in refrigeration condition. In order to improve the quality and prolong the shelf life of fresh meat, a refrigeration method based on ultrasonic atomizing humidification was proposed.【Method】Taking the pork sold in an open refrigerated display cabinet as the material, the influence of ultrasonic atomizing humidification on the shelf quality of pork was studied, and the changes of quality parameters such as shear force, color difference, cooking loss rate and pH of pork within 24 h in temperature control (TC) and temperature and humidity control (THC) conditions.【Result】The pork shear force changed little compared with the initial value after 12 h of TC condition, but rapidly decreased to 65.2N after 24 h of storage. The shear force of pork rapidly decreased within 12 h, and remained at around 86 N during 12-24 h in THC condition. In both conditions, L*, a* and b* showed similar trends over time, but L* in TC condition was higher than THC condition, while a* and b* were lower than THC condition. After 24 h refrigerated sales, the number of pork microorganisms under the two conditions were 28 000 and 149 713 CFU/mL, respectively. The change of pork microbial number during refrigerated sales was related to the change of color difference. The cooking loss rate showed similar trend under the two conditions over time, and there was little difference between them after 12 h. The cooking loss rate under two conditions were 26.2% and 24.6%, respectively. After 24 h refrigerated sales, the pH of pork under TC condition and THC condition decreased by 0.4 and 0.2, respectively, and the pork under THC condition belonged to the prime meat. The temperature and relative humidity in the refrigerated display cabinet under two working conditions showed similar trend of decreasing to rising in a single refrigeration cycle. The minimum temperature of TC condition in the cabinet was 1.2 ℃ higher than that of THC condition. The variation trend and amplitude of relative humidity under two working conditions were similar.【Conclusion】THC condition slowed down the shear force and pH drop rate of pork, reduce the cooking loss rate of pork, but the number of microorganisms in THC condition is 5.3 times of that in TC condition. The research results have a significant reference for improving the shelf quality of pork and optimizing the parameters of refrigerated display cabinet.

Algal blooms negatively impact the water quality of reservoirs; however, the role of dissolved organic matter (DOM) in bloom formation in reservoirs has not been investigated. Therefore, we assessed the compositions of sediment- and soil-derived DOM and their effects on the growth, physiology, and photosynthetic activity of Microcystis aeruginosa, Anabaena sp., Chlamydomonas sp., and Peridiniopsis sp. (bloom-forming species). Sediment DOM promoted the growth of all algal species, whereas soil DOM significantly promoted the growth of Chlamydomonas sp. and Peridiniopsis sp.; this effect was due to enhanced stress tolerance and photosynthetic efficiency exhibited by these algae under DOM treatment. However, soil DOM slightly inhibited the growth of Anabaena sp. by increasing reactive oxygen species levels and inactivating some photosystem II reaction centers. The tyrosine-like substance, humic acid-like substances, and unsaturated aliphatic compounds were the main DOM components that affected algal growth. The findings of this study will provide a theoretical foundation for the development of bloom-prevention strategies for river-type reservoirs.

Abstract This study shows residual surface carbon’s influence on photocathodes’ quantum efficiency based on p-GaN grown on sapphire by metal organic chemical vapor deposition. An X-ray photoelectron spectrometer (XPS) built in an ultrahigh vacuum system allowed the in-situ monitoring of the photocathode surface beginning immediately after their cleaning and throughout the activation and degradation processes. An atomically clean surface is necessary to achieve a negative electron affinity, which is the main prerequisite for high quantum efficiency. The p-GaN samples were cleaned with ethanol and underwent a sub-sequential thermal vacuum cleaning. Although carbon and oxygen contaminations are expected to be undesired impurities from the metal organic chemical vapor deposition, which remained on the surface, p-GaN could still form a negative electron affinity surface when exclusively activated with cesium. After the activation with cesium, a shift to a higher binding energy of the photoemission peaks was observed, and a new species, a so-called cesium carbide, was formed, growing over time. The XPS data elucidated the critical role of these cesium carbide species in photocathode degradation. The X-ray damage to the p-GaN:Cs photocathodes, especially the influence on the cesium, was additionally discussed.

The space of the mine inverter is closed. The internal power device itself will produce a lot of heat in the operation process, which is easy to produce thermal degradation and thermal failure. In the existing research, a certain power device or a radiator of the mine inverter is analyzed independently. The heat exchange effect among the power device or the radiator is not considered. The combination with the running state of the mine inverter is not close enough. Therefore, the deviation between the heat generation and heat transfer processes and the actual situation is large. This reduces the accuracy and comprehensiveness of the heat dissipation performance analysis. In order to the above problems, taking the 630 kW/1 140 V four-quadrant mine inverter as the research object, the heat dissipation performance of the mine inverter is analyzed based on integrated model . A topological model of the main circuit of the mine inverter considering equivalent resistance is established. The electrical characteristics of the bus bar and the cable, the charge/discharge resistance, the absorption resistance, the IGBT module and the output reactor are analyzed, and the power loss is calculated. The cooling system of the inverter is optimized by forced water cooling + air cooling + natural cooling. The IGBT module and the absorption resistor are arranged on the substrate of the water-cooling radiator. The fan is configured to accelerate the heat exchange efficiency of the output reactor, and other power devices dissipate heat naturally. Based on the integrated model, the temperature field characteristics and heat transfer characteristics of the mine inverter are numerically simulated and analyzed. The correctness of the temperature field simulation based on the integrated model and the effectiveness of the heat dissipation design are verified by building the loading test platform of mineing inverter . The results show the following points. ① Under the heat transfer of conduction, convection and radiation of the internal power devices, the temperature of the flameproof enclosure is higher than the ambient temperature. The lowest temperature is 36 ℃. The temperature of the rear substrate is higher than that of the other flameproof surfaces, and the highest temperature can reach 70 ℃. The temperature of the internal components of the mine inverter is not higher than 80 ℃, which is far lower than the specified value of relevant standards. The mine inverter has good heat dissipation performance. The temperature of IGBT module is the highest, the temperature of the bus bar assembly is the second, and the temperature of the DC filter capacitor assembly is the lowest. ② The power device in the process of charging has a larger loss. But because of the short charging time, the loss will not cause severe changes in temperature. The instantaneous temperature of the power device is not more than 59 ℃. The maximum instantaneous temperature of the discharge resistance can reach 267 ℃, and the action time above 100 ℃ is 200 seconds. The high-temperature impact resistance of the trapezoidal aluminum shell resistor can meet the application scenario. It does not form a thermal stress cycle, and will not produce thermal breakdown and thermal failure. ③ The temperature of each power device tends to be stable gradually after 2-3 h. The experimental and simulation results of each calibration temperature measurement point keep good consistency in the overall trend.

Background: Allergen immunotherapy is the only etiological treatment for allergic rhinitis. Objective: To analyze the efficacy, safety, and mechanism of subcutaneous immunotherapy (SCIT). Methods: The efficacy, safety, and serum immunological changes of 3 modes of subcutaneous immunotherapy were compared. Peripheral blood mononuclear cells (PBMC) transcriptome changes were obtained on the Illumina sequencing platforms. We confirmed differentially expressed genes (DEGs) by quantitative real-time polymerase chain reaction (PCR). The DEGs were analyzed by gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), and protein-protein interaction (PPI) networks. The correlation between the common DEGs and clinical indicators was analyzed by Origin 2022. Results: The 3 SCITs were all effective after 1 year. The Combined Symptom and Medication Score (CSMS) and Visual Analog Score (VAS) in rush immunotherapy (RIT) are lowest after 24 and 48 weeks of treatment among the 3 groups. After treatment, the levels of sIgE, sIgE/tIgE, Th2 cytokines, Th17 cytokines, and percentage of peripheral eosinophils (EOS%) decreased significantly (P＜0.05), while the levels of Th1 type cytokines did not change significantly. Transcriptome analysis identified 24, 24, and 91 DEGs at W3 and 42, 52, 175 DEGs at W7 in conventional immunotherapy (CIT), cluster immunotherapy (CLIT), and RIT groups, respectively. The pathways and functions involved in SCIT include secretion of Th1/2 cytokines, immune cell differentiation. Unlike CIT and CLIT, DEGs are also involved in T cell tolerance induction, T cell anergy, and lymphocyte anergy in RIT. CXCR1, CXCR2, and IER3 had a specific effect on reflecting the improvement of symptoms in allergic rhinitis patients with SCIT. Conclusion: The clinical efficacy of RIT appeared earlier than CIT and CLIT. Clinicians can use the highly conserved gene expression profile to evaluate responses to immunotherapy.

BackgroundThe coronavirus disease 2019 (COVID-19) pandemic has exerted a profound influence on humans. Increasing evidence shows that immune response is crucial in influencing the risk of infection and disease severity. Observational studies suggest an association between COVID‐19 and immunoglobulin G (IgG) N-glycosylation traits, but the causal relevance of these traits in COVID-19 susceptibility and severity remains controversial.MethodsWe conducted a two-sample Mendelian randomization (MR) analysis to explore the causal association between 77 IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity using summary-level data from genome-wide association studies (GWAS) and applying multiple methods including inverse-variance weighting (IVW), MR Egger, and weighted median. We also used Cochran’s Q statistic and leave-one-out analysis to detect heterogeneity across each single nucleotide polymorphism (SNP). Additionally, we used the MR-Egger intercept test, MR-PRESSO global test, and PhenoScanner tool to detect and remove SNPs with horizontal pleiotropy and to ensure the reliability of our results.ResultsWe found significant causal associations between genetically predicted IgG N-glycosylation traits and COVID-19 susceptibility, hospitalization, and severity. Specifically, we observed reduced risk of COVID-19 with the genetically predicted increased IgG N-glycan trait IGP45 (OR = 0.95, 95% CI = 0.92–0.98; FDR = 0.019). IGP22 and IGP30 were associated with a higher risk of COVID-19 hospitalization and severity. Two (IGP2 and IGP77) and five (IGP10, IGP14, IGP34, IGP36, and IGP50) IgG N-glycosylation traits were causally associated with a decreased risk of COVID-19 hospitalization and severity, respectively. Sensitivity analyses did not identify any horizontal pleiotropy.ConclusionsOur study provides evidence that genetically elevated IgG N-glycosylation traits may have a causal effect on diverse COVID-19 outcomes. Our findings have potential implications for developing targeted interventions to improve COVID-19 outcomes by modulating IgG N-glycosylation levels.

Background: Sudden cardiac death (SCD), unexpected death based on sudden cardiac ejection cessation, accounts for 15–20% of unnatural deaths in developed countries. Primary electrical disorders (PEDs), a group of cardiac rhythm abnormalities without detectable structural heart disease, are a major cause of SCD in people younger than 35 years of age. Cardiac muscle contraction and relaxation are triggered by the action potential (AP), which is generated by ionic changes across the cell membrane. Thus, PEDs are influenced by mutations in AP-associated genes, such as KCNE1 and RYR2 . Methods: We recruited six patients with SCD and 42 patients with arrhythmia with onset under the age of 25, and used targeted sequencing to determine the genetic etiologies. Results: We identified five mutations ( RYR2 : c.12269C>T, p.P4090L; KCNE1 : c.169T>C, p.F57L; KCNQ1 : c.853A>C, p.K285Q; KCNH2 : c.793T>C, p.C265R, and TRPM4 : c.2985_3012del, p.E996Gfs*118) in five families with PED/SCD. Conclusions: We detected five mutations and expanded the mutation spectrum of PED-associated genes, thus contributing to the clinical diagnosis of PED.

Abstract Aims/Introduction Metals play an important role in diabetes mellitus. This cross‐sectional study aimed to evaluate the overall, individual and interactive effects of multi‐metal exposure on the prevalence of diabetes mellitus, impaired fasting glucose (IFG) rate and fasting blood glucose (FBG) levels. Materials and Methods The FBG levels of a study population from a cadmium (Cd)‐polluted area (n = 250) and an unpolluted area (n = 204), and the metal levels, including magnesium, calcium (Ca), iron (Fe), zinc (Zn), arsenic (As), Cd, copper and lead (Pb) in blood and urine were detected. The study population was divided into a normal fasting glucose group, an IFG group and a diabetes mellitus group on the basis of FBG levels. Results The IFG rate and diabetes mellitus prevalence were negatively associated with blood Cd and urine Zn levels (IFG rate: odds ratio [OR] 0.780, 95% confidence interval [CI] 0.655–0.928; OR 0.622, 95% CI 0.465–0.831. Diabetes mellitus prevalence: OR 0.506, 95% CI 0.288–0.888; OR 0.609, 95% CI 0.395–0.939), the IFG rate was positively associated with urine Fe levels (OR 1.876, 95% CI 1.290–2.778), and diabetes mellitus prevalence was positively associated with urine Pb and blood Fe levels (OR 1.185, 95% CI 1.022–1.376; OR 1.008, 95% CI 1.001–1.014). A linear negative correlation was observed between FBG levels and blood Cd, and non‐linear inverted U‐shaped associations were found between FBG levels and Zn, Pb and copper in urine. Conclusions This research suggests that multi‐metal exposure, especially Cd, Fe, Zn, copper and Pb, is linked to diabetes mellitus, and the interactive effects of multiple metals require further exploration.

Abstract Background The COVID-19 pandemic has increasingly accelerated the publication pace of scientific literature. How to efficiently curate and index this large amount of biomedical literature under the current crisis is of great importance. Previous literature indexing is mainly performed by human experts using Medical Subject Headings (MeSH), which is labor-intensive and time-consuming. Therefore, to alleviate the expensive time consumption and monetary cost, there is an urgent need for automatic semantic indexing technologies for the emerging COVID-19 domain. Results In this research, to investigate the semantic indexing problem for COVID-19, we first construct the new COVID-19 Semantic Indexing dataset, which consists of more than 80 thousand biomedical articles. We then propose a novel semantic indexing framework based on the multi-probe attention neural network (MPANN) to address the COVID-19 semantic indexing problem. Specifically, we employ a k-nearest neighbour based MeSH masking approach to generate candidate topic terms for each input article. We encode and feed the selected candidate terms as well as other contextual information as probes into the downstream attention-based neural network. Each semantic probe carries specific aspects of biomedical knowledge and provides informatively discriminative features for the input article. After extracting the semantic features at both term-level and document-level through the attention-based neural network, MPANN adopts a linear multi-view classifier to conduct the final topic prediction for COVID-19 semantic indexing. Conclusion The experimental results suggest that MPANN promises to represent the semantic features of biomedical texts and is effective in predicting semantic topics for COVID-19 related biomedical articles.

Measurement(s) RNA-seq gene expression profiling assay • ATAC-Seq Technology Type(s) RNA-seq of coding RNA from single cells • Single cell ATAC-seq (cell index) Sample Characteristic - Organism Rhinolophus affinis

Abstract Reticulon 3 (RTN3), an endoplasmic reticulum protein, is crucial in neurodegenerative and kidney diseases. However, the role of RTN3 in liver tissues has not been described. Here, we employed public datasets, patients, and several animal models to explore the role of RTN3 in nonalcoholic fatty liver disease (NAFLD). The underlying mechanisms were studied in primary hepatocytes and L02 cells in vitro. We found an increased expression of RTN3 in NAFLD patients, high‐fat diet mice, and oxidized low‐density lipoprotein‐treated L02 cells. The RTN3 transgenic mice exhibited the phenotypes of fatty liver and lipid accumulation. Single‐cell RNA sequencing analysis indicated that increased RTN3 might induce mitochondrial dysfunction. We further showed this in primary hepatocytes, the L02 cell line, and the Caenorhabditis elegans strain. Mechanistically, RTN3 regulated these events through its interactions with glucose‐regulated protein 78 (GRP78), which further inhibited the adenosine 5 monophosphate‐activated protein kinase (AMPK)–isocitrate dehydrogenase 2 (IDH2) pathway. In the end, knockout of RTN3 relieved fatty liver and mitochondrial dysfunction. Our study indicated that RTN3 was important in NAFLD and lipid catabolism and that an increase in RTN3 in the liver might be a risk factor for nonalcoholic steatohepatitis and NAFLD.

Short stature (OMIM: 165800) is a common pediatric disorder. Any abnormality in the cartilage formation of the growth plate can cause short stature. Aggrecan, encoded by ACAN, is an important component of the extracellular matrix. Mutations in ACAN have been reported to cause short stature. In the present study, we enrolled a Chinese family with short stature and advanced bone age across three generations. Whole-exome sequencing (WES) was performed on the proband to detect the candidate genes causing short stature in family. A novel heterozygous frameshift mutation (NM_013227.3:c.7230delT; NP_001356197.1: p. Phe2410Leufs*9) of the ACAN gene was confirmed to be a genetic lesion in this family. This variant, which was located in a functional site globular 3 (G3) domain of ACAN and predicted to be deleterious by informatics programs, was co-segregated with the affected family members by performing Sanger sequencing. Literatures review of growth hormone (GH) treatment outcome of all previously reported ACAN patients suggesting that the G3 domain of ACAN may be critical in the development of short stature and growth hormone treatment. These findings not only contribute to the genetic diagnosis and counseling of the family, but will also expand the mutation spectrum of ACAN.

Background: Congenital contractural arachnodactyly (CCA) is an autosomal dominant connective tissue disorder with clinical features of arthrogryposis, arachnodactyly, crumpled ears, scoliosis, and muscular hypoplasia. The heterozygous pathogenic variants in FBN2 have been shown to cause CCA. Fibrillin-2 is related to the elasticity of the tissue and has been demonstrated to play an important role in the constitution of extracellular microfibrils in elastic fibers, providing strength and flexibility to the connective tissue that sustains the body’s joints and organs.Methods: We recruited two Chinese families with arachnodactyly and bilateral arthrogryposis of the fingers. Whole-exome sequencing (WES) and co-segregation analysis were employed to identify their genetic etiologies. Three-dimensional protein models were used to analyze the pathogenic mechanism of the identified variants.Results: We have reported two CCA families and identified two novel missense variants in FBN2 (NM_001999.3: c.4093T>C, p.C1365R and c.2384G>T, p.C795F). The structural models of the mutant FBN2 protein in rats exhibited that both the variants could break disulfide bonds.Conclusion: We detected two FBN2 variants in two families with CCA. Our description expands the genetic profile of CCA and emphasizes the pathogenicity of disulfide bond disruption in FBN2.

Through the analysis and processing of monitoring data, the prognostics health management (PHM) technology for mine inverter power devices can extract signal characteristics, locate the open circuit fault position of power devices, predict the life of power devices and improve the safety and reliability of mine inverter. This paper introduces the principle and research status of signal characteristics extraction method in PHM technology, including coordinate transformation method, spectrum analysis method, wavelet analysis method, empirical mode decomposition method. This paper introduces the principle and research status of power device open circuit fault diagnosis method in PHM technology, including state estimation method, neural network method, support vector machine method. This paper introduces the principle and research status of power device life prediction method in PHM technology, including analytical model method, physical model method, data-driven method. The above methods are compared from five aspects, including implementation difficulty, timeliness, immunity, accuracy and data demand. The signal characteristic extraction method is single. There is open-circuit fault of multiple power devices of mine inverter. The life prediction of power devices based on data-driven method fails to consider the variable working conditions of inverter. In order to solve the above problems, the research directions of PHM technology for mine inverter power devices are proposed. The directions include signal characteristic extraction based on multi-method fusion, open-circuit fault diagnosis of multiple power devices based on intelligent algorithm, fault-tolerant control and health management, and power device life prediction under variable working conditions.

Organic color centers in single-walled carbon nanotubes can act as single-photon sources in the telecom range. Here the authors report the functionalization of air-suspended nanotubes through a vapor-phase photochemical reaction, demonstrating a further tailoring of quantum emitter materials.

The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.

Dendrite growth of lithium (Li) metal anode severely hinders its practical application, while the situation becomes more serious at low temperatures due to the sluggish kinetics of Li-ion diffusion. This perspective is intended to clearly understand the energy chemistry of low-temperature Li metal batteries (LMBs). The low-temperature chemistries between LMBs and traditional Li-ion batteries are firstly compared to figure out the features of the low-temperature LMBs. Li deposition behaviors at low temperatures are then discussed concerning the variation in Li-ion diffusion behaviors and solid electrolyte interphase (SEI) features. Subsequently, the strategies to enhance the diffusion kinetics of Li ions and suppress dendrite growth including designing electrolytes and electrode/electrolyte interfaces are analyzed. Finally, conclusions and outlooks are drawn to shed lights on the future design of high-performance low-temperature LMBs.

BackgroundCampomelic dysplasia (CD) is an autosomal dominant skeletal dysplasia syndrome characterized by shortness and bowing of lower extremities, and often accompanied by XY sex reversal. Heterozygous pathogenic variants of SOX9 or rearrangement involving the long arm of chromosome 17 are the causes of disease. However, evidence for pathogenesis of SOX9 haploinsufficiency is insufficient.MethodsWe enrolled a Chinese family where the fetus was diagnosed with CD. The affected fetus was selected for whole-exome sequencing to identify the pathogenic mutations in this family.ResultsAfter data filtering, a novel non-sense SOX9 variant (NM_000346.3; c.1249C > T; p.Q417*) was identified as the pathogenic lesion in the fetus. Further co-segregation analysis using Sanger sequencing confirmed that this novel SOX9 mutation (c.1249C > T; p.Q417*) was a de novo mutation in the affected fetus. This terminated codon mutation identified by bioinformatics was located at an evolutionarily conserved site of SOX9. The bioinformatics-based analysis predicted this variant was pathogenic and affected SOX9 transactivation activity.ConclusionCD is a rare condition, which connected with SOX9 tightly. We identified a novel heterozygous SOX9 variant (p.Q417*) in a Chinese CD family. Our study supports the putative reduced transactivation of SOX9 variants in the pathogenicity of CD.

Here the authors report single-nucleus RNA sequencing for several anatomical locations in 11 species, including cat, dog, hamster, lizard, goat, rabbit, duck, pigeon, pangolin, tiger, and deer, highlighting coexpression of SARS-CoV-2 entry factors ACE2 and TMPRSS2.

Abstract The pursuit of sustainable energy has a great request for advanced energy storage devices. Lithium metal batteries are regarded as a potential electrochemical storage system because of the extremely high capacity and the most negative electrochemical potential of lithium metal anode. Dead lithium formed in the stripping process significantly contributes to the low efficiency and short lifespan of rechargeable lithium metal batteries. This review displays a critical review on the current research status about the stripping electrochemistry of lithium metal anode. The significance of stripping process to a robust lithium metal anode is emphasized. The stripping models in different electrochemical scenarios are discussed. Specific attention is paid to the understanding for the electrochemical principles of atom diffusion, electrochemical reaction, ion diffusion in solid electrolyte interphase (SEI), and electron transfer with the purpose to strengthen the insights into the behavior of lithium electrode stripping. The factors affecting stripping processes and corresponding solutions are summarized and categorized as follows: surface physics, SEI, operational and external factors. This review affords fresh insights to explore the lithium anode and design robust lithium metal batteries based on the comprehensive understanding of the stripping electrochemistry.

At present, the methods of optimizing busbar structure parameters, changing gate drive resistance and designing absorption circuit are commonly used to suppress the peak voltage of insulated gate bipolar transistor (IGBT) in mine-used inverter caused by stray inductance. But the existing research has not revealed the coordination and unification relationship between the methods and their coordination and optimization criteria. In order to solve this problem, taking BPJ5-630-1140 type mine-used four-quadrant inverter as the research object, based on the analysis of the influence of stray inductance on the electric-thermal performance of IGBT, a coordinated optimization method of IGBT peak voltage suppression is proposed. ① The method analyzes the influence of busbar structure parameters and grid drive resistance on IGBT peak voltage and power loss. The results show that the peak voltage and power loss of IGBT increase with the AC busbar length increase and the AC busbar width decrease. With the increase of gate drive resistance, IGBT peak voltage decreases and power loss increases. ② The diode clamped absorption circuit is designed, which is verified by experiments to reduce the peak voltage and power loss of IGBT. ③ Considering that the AC busbar width has no effect on the layout and heat dissipation performance of IGBT, the gate drive resistance and the AC busbar length are selected as decision variables. The BP neural network and elitist non-dominated sorting genetic algorithm (BP-NSGAⅡ) are used to achieve multi-objective optimization of IGBT peak voltage, the maximum IGBT temperature and the maximum temperature of radiator surface. The experimented results show that when the maximum temperature of radiator surface is 55-65 ℃ and the maximum IGBT temperature is 74-80 ℃, the minimum IGBT peak voltage is 1861 V. The corresponding grid drive resistance is 5 Ω, the AC busbar length is 300 mm, and the AC busbar width is 200 mm. The optimized IGBT peak voltage of BPJ5-630-1140 type inventer is 1 856 V, which is 35% lower than 2 856 V before optimization. The IGBT peak voltage is effectively suppressed, and the operation reliability of the mine-used inverter is improved.

Despite the clinical success in the treatment of several types of cancers, the immune checkpoint inhibitors (ICIs) show limited response rates in cancers with low tumor mutational burden (TMB) and antigenicity. Here, we aim to enhance tumor antigenicity at the protein translation level by using non-proteinogenic amino acids (NPAs) that cause regional mistranslation and mutated proteins. We utilized proline analogue azetidine-2-carboxylic acid (AZA), which can be discharged into proline tRNA by prolyl-tRNA synthetase, leading to the generation of a proportion of mutated proteins with proline residues substituted with Aze in tumor cells undergoing active protein synthesis. To specifically produce mutated proteins in tumor cells, the anti-Cd44 antibody-coated liposome nanoparticles (NPs) were used to deliver Aze specifically into the breast cancer cells. The Aze delivered by NPs can be incorporated into proteins in the 4T1 tumor allografts in mice, resulting in the activation of cellular immune responses and hence the significant inhibition of the growth of 4T1 allografts and the pulmonary metastasis, eventually prolonging the survival of tumor-bearing mice. Interestingly, Aze increases the response of 4T1 breast cancer allografts to anti-PD1 antibody treatment, suggesting Aze is able to sensitize tumors to the ICIs treatment in the immunotherapy of tumors.

Abstract Background Ovarian cancer, a highly metastatic malignancy, has benefited tremendously from advances in modern human genomics. However, the genomic variations related to the metastasis remains unclear. Methods We filtered various significant genes (n = 6722) associated with metastasis within a large-scale functional genomic CRISPR/Cas9 knock-out library including 122,756 single guide RNAs, and identified ITK (IL2 Inducible T Cell Kinase) as a potential cancer suppressor gene for ovarian cancer metastasis. Downstream bioinformatic analysis was performed for ITK using public databases. Results We found that patients in low-ITK group had poor prognosis and more distant metastasis than those in high-ITK group in TCGA and GEO databases. We also demonstrated that ITK combined with the clinical factors could accurately predict prognosis through multiple Cox regression analysis and ROC analysis. Moreover, alterations correlated with distant metastasis emereged with significantly increased expression in SAMRCD1 in low-ITK group, but CD244 and SOCS1 in high-ITK group. Integrated analysis revealed dysregulated molecular processes including predominantly oncogenic signaling pathways in low-ITK group but immune related pathways in high-ITK group, which suggested ITK might inhibit distant metastasis in ovarian cancer. Furtherly, deconvolution of the cellular composition of all samples validated the close correlation between ITK and immune related function especially for cytotoxic lymphocytes. Conclusions Together, these data provide insights into the potential role of ITK, with implications for the future development of tansformative ovarian cancer therapeutics.

Long-chain alkyl diols (LCDs) can be used as organic geochemical proxies for paleoceanographic change, especially in marginal sea areas where large volumes of sediments are deposited rapidly and continuously. However, little is known about the applicability and response on a millennium scale in relation with existing records in those sediments. We reconstruct changes in upwelling and terrestrial organic matter (OM) input in core sediments from the Zhejiang Fujian coastal station (T08) and Yangtze River Estuary station (T06) in the inner shelf of the East China Sea (ECS) over the last millennium, using the LCD based proxies: diol index 2 (DI-2), and FC321,15-diol. Our results show that DI-2 values ([(C28+C30)1,14-diols]/([(C28+C30)1,13-diols]+[(C28+C30)1,14-diols])) at T08 decrease significantly during 600–400 yr BP but increase gradually after 400 yr BP. The FC321,15-diol proxy ([C321,15-diol]×100/([(C28+C30)1,13-diols]+[(C30+C32)1,15-diols])) at T06 shows marked fluctuations during 1000–800 yr BP, followed by a significant decline during 800–500 yr BP but a subsequent increase from 500 to 300 yr BP. We find that variations in DI-2 values are broadly consistent with changes in the strength of the East Asian Summer Monsoon (EASM) and the Kuroshio Current and are likely linked to changes in the frequency and intensity of the El Niño-Southern Oscillation (ENSO). The increased strength of the EASM causes greater offshore movement of the upper layer of seawater, which in turn triggers upwelling of bottom waters formed by Kuroshio subsurface waters. We find that variations in FC321,15-diol proxy are controlled mainly by the East Asian Winter Monsoon (EAWM) and the Yangtze River discharge. By increasing the strength of the EAWM, southward transportation of material deposited in the estuary of the Yangtze River by the ECS coastal currents is promoted. In addition, we synthesize records of other organic geochemical indicators nearby core sediments in the ECS; these records emphasize the importance of reconstructing the evolutionary history of upwelling and subdividing the relative inputs of terrestrial OM. Our study provides a new means for reconstructing the evolution of upwelling and terrestrial OM input in the inner shelf of the ECS over the last millennium.

Metallo β-Lactamases (MBLs) degrade most clinical β-lactam antibiotics, especially Carbapenem, posing a huge threat to global health. Studies on environmental MBLs are important for risk assessment of the MBLs transmission among connected habitats, and between environment and human. Here, we described a novel metallo β-Lactamases, named SZM-1 (Shenzhen metallo-β-lactamase), from an Arenimonas metagenome-assembled genome recovered from the river sediment in the Shenzhen Bay area, south China. Phylogenetic analysis, primary sequence comparison, structural modeling suggested that the SZM-1 belongs to B1 MBL family, likely harboring a typical di-zinc catalytic center. Furthermore, the gene encoding the MBLs was cloned into Escherichia coli TOP10 for Carba NP test and antimicrobial susceptibility test. The results indicated that the SZM-1 had carbapenemase activity, and conferred the carrier to increased resistance toward carbapenems. Taken together, our results raise alarms about the emergence and spread of the SZM-1, and suggest further surveillance, especially in hospital settings and clinical isolates, to determine whether blaSZM–1 is a mobilizable antibiotic resistance.

Background: Chronic kidney disease, a global public health problem, results in kidney damage or a gradual decline in the glomerular filtration rate. Alport syndrome is commonly characterized by chronic glomerulonephritis caused by a structural disorder in the glomerular basement membrane. Currently, three disease-causing genes, namely collagen type IV alpha 3–5 (COL4A3, COL4A4, and COL4A5), have been associated with the occurrence of Alport syndrome.Methods: We enrolled a Chinese family where the affected individuals suffered from recurrent hematuria and proteinuria. The proband was selected for whole-exome sequencing to identify the pathogenic mutations in this family.Results: After data filtering, a novel heterozygous COL4A4 variant (NM_000092: c.853G>A/p. G285A) was identified as the putative genetic lesion in the affected individuals. Further co-segregation analysis using Sanger sequencing confirmed that this novel COL4A4 mutation (c.853G>A/p. G285A) exists only in the affected individuals and is absent in other healthy family members as well as in the control cohort of 200 individuals from the same locality. According to American College of Medical Genetics and Genomics guidelines, the mutation was classified as ‘potentially pathogenic’. A bioinformatics-based prediction analysis revealed that this mutation is pathogenic and may disrupt the structure and function of type IV collagen. This variant is located at an evolutionarily conserved site of COL4A4.Conclusion: In this study, we identified a novel heterozygous COL4A4 variant (c.853G>A) in a Chinese AS family and assisted to diagnose this AS proband as autosomal-dominant Alport syndrome (ADAS). Our study expands the spectrum of Alport syndrome mutations and contributes to the genetic counseling and diagnosis of patients with Alport syndrome.