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Summary: Background: In China, dementia poses a significant public health challenge, exacerbated by an ageing population and lifestyle changes. This study assesses the temporal trends and disparities in the population-attributable fractions (PAFs) of modifiable risk factors (MRFs) for new-onset dementia from 2011 to 2018. Methods: We used data from the China Health and Retirement Longitudinal Study (CHARLS), covering 75,214 person-waves. We calculated PAFs for 12 MRFs identified by the Lancet Commission (including six early-to mid-life factors and six late-life factors). We also determined the individual weighted PAFs (IW-PAFs) for each risk factor. Subgroup analyses were conducted by sex, socio-economic status (SES), and geographic location. Findings: The overall PAF for dementia MRFs had a slight increase from 45.36% in 2011 to 52.46% in 2018, yet this change wasn’t statistically significant. During 2011–2018, the most contributing modifiable risk was low education (average IW-PAF 11.3%), followed by depression, hypertension, smoking, and physical inactivity. Over the eight-year period, IW-PAFs for risk factors like low education, hypertension, hearing loss, smoking, and air pollution showed decreasing trends, while others increased, but none of these changes were statistically significant. Sex-specific analysis revealed higher IW-PAFs for traumatic brain injury (TBI), social isolation, and depression in women, and for alcohol and smoking in men. The decline in IW-PAF for men’s hearing loss were significant. Lower-income individuals had higher overall MRF PAFs, largely due to later-life factors like depression. Early-life factors, such as TBI and low education, also contributed to SES disparities. Rural areas reported higher overall MRF PAFs, driven by factors like depression, low education, and hearing loss. The study also found that the gap in MRF PAFs across different SES groups or regions either remained constant or increased over the study period. Interpretation: The study reveals a slight but non-significant increase in dementia’s MRF PAF in China, underscoring the persistent relevance of these risk factors. The findings highlight the need for targeted public health strategies, considering the demographic and regional differences, to effectively tackle and reduce dementia risk in China’s diverse population. Funding: This work was supported by the PKU Young Scholarship in Global Health and Development.

Summary: The exploration of renewable alternatives to fossil fuels for chemical production is indispensable to achieve the ultimate goals of sustainable development. Chitin biomass is an abundant platform feedstock that naturally bears both nitrogen and carbon atoms to produce nitrogen-containing chemicals (including organonitrogen ones and inorganic ammonia). The expansion of biobased chemicals toward nitrogen-containing ones can elevate the economic competitiveness and benefit the biorefinery scheme. This review aims to provide an up-to-date summary on the overall advances of the chitin biorefinery for nitrogen-containing chemical production, with an emphasis on the design of the catalytic systems. Catalyst design, solvent selection, parametric effect, and reaction mechanisms have been scrutinized for different transformation strategies. Future prospectives on chitin biorefinery have also been outlined.

We successfully developed an induced pluripotent stem cell (iPSC) line, SYSUSHi001-A, from the peripheral blood mononuclear cells (PBMC) of a patient with Acute Myeloid Leukemia, harboring two genetic mutations (XPO1: c.591-4_591-3dupTT; PALB2: c.3296C > T; p.T1099M). This iPSC line was facilitated through the use of episomal plasmids encoding OCT4, SOX2, KLF4, L-MYC, and human miR-302. The SYSUSHi001-A iPSC line exhibited characteristic embryonic stem cell-like morphology, maintained the XPO1 and PALB2 mutations, expressed key pluripotency markers, preserved a normal karyotype (46, XY), and demonstrated the ability to differentiate into cells from all three germ layers in vitro.

Study region: Guizhou Province, Southwest China Study focus: This study aims to estimate the hydraulic conductivity (Kh) of the weathered rock fractures (epikarst) based on the best fitting of observed water head in 105 slug tests in the study sites. Specifically, comparisons of the estimated results from the analytical and numerical methods reveal the effects of changes in fracture flow conditions (e.g., steady and non-steady) on Kh for various fracture apertures and soil fillings. New hydrological insights for the region: The results comparatively show that Kh from the analytical solution of steady flow was significantly underestimated, and the numerical modeling of the non-linear and unsteady flow can improve the water head fitting when the Reynolds number (Re) > 17.27. The optimized Kh ranges 0.014–2673 m/d and the mean value of Kh is about 100 times the median value, suggesting that epikarst flow might be controlled by a limited number of larger fractures. Moreover, the soil filling in large fractures (>10 mm) creates a turning point of the exponential increase of Kh with d. Comparatively, the naturally full-filling fractures resemble the soil matrix with a low Kh, and the partial-filling fractures can create preferential flow around the soil-rock interfaces with a high Kh. These results fundamentally improve our understanding of water infiltration, retention, and availability for plant uses in the karst areas of southwest China.

Blastocystis is a parasitic protist that can infect humans and various domestic and wild animals. However, there is limited research on the prevalence of this parasite among rodents, particularly those living in pig farm settings. Therefore, to investigate the occurrence, molecular characterization, and zoonotic potential of Blastocystis among rodents within pig farm environments, we conducted an investigation of 227 rodents and shrews from 34 pig farms located in Henan, Shaanxi, and Shanxi provinces of China using nested PCR of the SSU rRNA gene of Blastocystis. The potential transmission and public health implications were also assessed from a One Health perspective. Blastocystis was detected in 86 (37.9%) fecal samples. The highest infection rate was observed among Ruttus norvegicus (73.7%, 42/58), followed by Ruttus tanezumi (30.1%, 41/136), and Mus musculus (12.0%, 3/25). However, it was not detected among individuals with Apodemus agrarius (n = 1) and Crocidura shantungensis (n = 7). Five known zoonotic Blastocystis subtypes (ST1–ST5) were identified, with ST4 (51.2%, 44/86) and ST5 (40.7%, 35/86) being the predominant ones, followed by ST1 (3.5%, 3/86), ST3 (3.5%, 3/86), and ST2 (1.2%, 1/86). ST4 was prevalent among R. norvegicus (83.3%, 35/42), while ST5 dominated R. tanezumi (70.7%, 29/41). Furthermore, ST5 exhibited the widest distribution at pig farm level, accounting for 65.0% (13/20) of Blastocystis-positive pig farms. This investigation presents the first documented Blastocystis infection in R. tanezumi and M. musculus, highlighting the predominant presence of the zoonotic ST5 subtype in rodents for the first time. The results demonstrate that sympatric rodents can serve as natural reservoirs for Blastocystis and play a role in its transmission. These findings provide information on the dynamics of rodent transmission and emphasize the potential public health threat posed by zoonotic Blastocystis subtypes spillover from pig farms.

As a local specialty of Tibet, Qingke baijiu (QB) is made from highland barley, and is referred to as the manufacturing process of light-aroma baijiu. Using highland barley in the Qu-making and the high-temperature stacking process of sauce-aroma baijiu results in a novel Qingke baijiu (NQB). This study analyzed two kinds of NQBs by GC-MS, GC×GC-MS, and GC-O-MS, and compared them with QB, light-aroma, strong-aroma, and sauce-aroma baijiu. A total of 346 volatile compounds and 60 aroma-active compounds were detected in NQB. There were 14 compounds with FD≥27 and OAVs ≥1. Although NQB and QB shared 39 volatile compounds, NQB has more than three times the overall concentration of volatile compounds than QB. In contrast to QB, NQB exhibited a richer flavor profile and a more intense fruity, floral, and acidic aroma. Meanwhile, the distilled grains and sorghum aroma were comparatively diminished.

Through statistical analysis of geological and hydrogeological data of the early mining section of a mine field in Wubao Mining Area, the main control factors affecting the water inrush from the floor of the main mining coal seam were determined. Fuzzy analytic hierarchy process（FAHP）and entropy weight method（EWM）were used to calculate the subjective and objective weights of each factor. The combination weights were calculated by addition synthesis method, range maximization method, game theory method and minimum discriminant information method, respectively. Combined with the vulnerability index method, the information fusion technology of GIS was used to obtain the water inrush vulnerability assessment zoning of the study area. The transition trend of the four evaluation results is basically the same, but there are some areas with different rating results. The Spearman rank correlation coefficient was used to optimize the evaluation results of four kinds of water inrush vulnerability. The results showed that the correlation coefficient between the vulnerability index ranking based on the minimum discriminant information method and the “reasonable ranking” was the highest. Therefore, it can be inferred that among the four vulnerability assessment results, the water inrush vulnerability assessment obtained by the combination of the minimum discriminant information method is the best.

Abstract The change of fracture propagation direction caused by stress interference between fractures is one of the main reasons that affect shale gas productivity. Natural fractures will be damaged by the induced stress, and the induced stress field produced by natural fracture damage will in turn affect the propagation of hydraulic fractures. Previous studies usually ignored the impact of stress field variation caused by natural fracture damage, leading to inaccurate fracture propagation simulation results. A new model for simulating hydraulic fracturing-induced stress field is established with consideration of the influence of natural fracture damage. Then, the natural fracture-induced stress is analyzed in open and closed fracture states. Through superposition of stress fields of natural fractures and hydraulic fractures, the interaction among open and closed natural fractures, reservoir and hydraulic fracture, and the corresponding fracture property evolution are studied. The results demonstrate that induced stress is not affected by elastic modulus and Poisson's ratio of the rock. The induced stress difference at the fracture tip is proportional to the net pressure and the length of hydraulic fractures. The results provide guidance for the optimal design of fracturing. When the deflection angle of hydraulic fracture is less than 90°, the maximum induced stress difference at the fracture tip decreases with the reduction in the deflection angle. When the deflection angle of hydraulic fracture is smaller than 90° or the deflection angle of natural fracture is smaller than 45°, the steering of hydraulic fracture is less hindered, which is beneficial to the formation of complex fracture network.

The introduction of reinforced concrete structures to China occurred in the late 19th century via Shanghai and other cities. While Shanghai has been extensively researched in terms of its reinforced concrete structures, Suzhou, located near Shanghai and one of the early adopters of reinforced concrete construction, has received less attention. This study aims to investigate the impact of reinforced concrete structures in early modern Suzhou, focusing on Cline Hall as a case study, which stands one of Suzhou’s earliest buildings with a reinforced concrete structure. Drawing on the close relationship between Suzhou and Shanghai in terms of architectural design, construction technology and materials. The study examines the opportunities for the introduction, the types and layouts of reinforced concrete structure systems, and the forms of materials in modern Suzhou (1919–1933). Additionally, material testing was conducted to provide a preliminary assessment of the aggregate ratios and durability of the reinforced concrete. This paper offers a foundation and recommendations for the conservation of Cline Hall, as well as other modern reinforced concrete buildings in Suzhou. By shedding light on the lesser-explored aspect of reinforced concrete heritage in modern Suzhou, this paper contributes to the broader understanding of architectural history and conservation practices.

Abstract Embryonic stem cells (ESCs) exhibit unique attributes of boundless self-renewal and pluripotency, making them invaluable for fundamental investigations and clinical endeavors. Previous examinations of microgravity effects on ESC self-renewal and differentiation have predominantly maintained a descriptive nature, constrained by limited experimental opportunities and techniques. In this investigation, we present compelling evidence derived from murine and human ESCs, demonstrating that simulated microgravity (SMG)-induced stress significantly impacts self-renewal and pluripotency through a previously unidentified conserved mechanism. Specifically, SMG induces the upregulation of heat shock protein genes, subsequently enhancing the expression of core pluripotency factors and activating the Wnt and/or LIF/STAT3 signaling pathways, thereby fostering ESC self-renewal. Notably, heightened Wnt pathway activity, facilitated by Tbx3 upregulation, prompts mesoendodermal differentiation in both murine and human ESCs under SMG conditions. Recognizing potential disparities between terrestrial SMG simulations and authentic microgravity, forthcoming space flight experiments are imperative to validate the impact of reduced gravity on ESC self-renewal and differentiation mechanisms.

Abstract We present a new ferroelectric nematic material, 4-((4′-((trans)-5-ethyloxan-2-yl)-2′,3,5,6′-tetrafluoro-[1,1′-biphenyl]-4-yl)difluoromethoxy)-2,6-difluorobenzonitrile (AUUQU-2-N) and its higher homologues, the molecular structures of which include fluorinated building blocks, an oxane ring, and a terminal cyano group, all contributing to a large molecular dipole moment of about 12.5 D. We observed that AUUQU-2-N has three distinct liquid crystal phases, two of which were found to be polar phases with a spontaneous electric polarization P s of up to 6 µC cm–2. The highest temperature phase is a common enantiotropic nematic (N) exhibiting only field-induced polarization. The lowest-temperature, monotropic phase proved to be a new example of the ferroelectric nematic phase (NF), evidenced by a single-peak polarization reversal current response, a giant imaginary dielectric permittivity on the order of 103, and the absence of any smectic layer X-ray diffraction peaks. The ordinary nematic phase N and the ferroelectric nematic phase NF are separated by an antiferroelectric liquid crystal phase which has low permittivity and a polarization reversal current exhibiting a characteristic double-peak response. In the polarizing light microscope, this antiferroelectric phase shows characteristic zig-zag defects, evidence of a layered structure. These observations suggest that this is another example of the recently discovered smectic ZA (SmZA) phase, having smectic layers with the molecular director parallel to the layer planes. The diffraction peaks from the smectic layering have not been observed to date but detailed 2D X-ray studies indicate the presence of additional short-range structures including smectic C-type correlations in all three phases—N, SmZA and NF—which may shed new light on the understanding of polar and antipolar order in these phases.

Abstract Purpose Cytokines regulate the interaction between the immune system and malignant tumors. Among them, interleukin-10 (IL-10) is a multifunctional anti-inflammatory cytokine mainly produced by immune cells. The correlation between gastric cancer and T/C single nucleotide polymorphism (SNP) of interleukin-10 (IL-10) promoter−819(rs1800871)was opaque and remained to be determined. We aim to explore the pertinence of gastric cancer and SNP of interleukin 10–819 by meta-analysis via five statistical models. Methods Databases including PubMed, Cochrane Library, Embase, the Scopus, and Google Scholars were comprehensively retrieved for the eligible studies on the related topic from inception to March 2022. Odds ratios (ORs) were generated for dichotomous variants by meta-analysis in each model via STATA 17.0 MP. The statistical models comprised recessive model, over-dominant model, allele model, co-dominant model and dominant model. Subgroup analysis was performed to investigate the difference across races as well as the source of heterogeneity if necessary. Results Eventually a total of 15 articles reporting 7779 patients were enrolled in our study. There were 2383 patients and 5396 controls, collectively. There was no correlation between gastric cancer and IL-10 819 in recessive model, co-dominant model or dominant model, and subgroup analysis showed that Asian, Latin American and Caucasian had no correlation with the risk of gastric cancer. In the allelic model, there was significant correlation between gastric cancer and IL-10 819 (OR = 3.96%, 95%CI: 3.28 to 3.78). In the over-dominant model, there is no correlation between gastric cancer and IL-10 819, but subgroup analysis uncovered significant vulnerability of Asian people with regard to gastric cancer. Conclusions In our study, both Asians, Latin Americans, and Europeans showed an increased risk of gastric cancer in the allelic model, whereas only Asians showed significant susceptibility in the super dominant model. Of course, more large cohort studies are needed to confirm our results.

Abstract Background Encephalitis caused by dengue virus (DENV) is considered a manifestation of severe dengue. Tanreqing injection (TRQ) is a well-known Chinese patented medicine, which has been used to treat brain-related disorders by inhibiting inflammation. Nevertheless, the effects of TRQ on DENV encephalitis have not been studied. The aim of this study was to evaluate the effects of TRQ on DENV encephalitis and to explore its potential mechanisms. Methods The cytotoxicity of TRQ was examined by MTT assay, and the anti-DENV activities of TRQ in BHK-21 baby hamster kidney fibroblast were evaluated through CCK-8 and plaque assays. The expression levels of NO, IL1B/IL-1β, TNFα and IL6 were measured by qRT‒PCR and ELISA in the BV2 murine microglial cell line. The inhibitory effects of TRQ on NLRP3 inflammasome activation in BV2 cells were examined by Western blotting, qRT‒PCR and ELISA. The effects of TRQ on HT22 mouse hippocampal neuronal cells were examined by CCK-8 assay, morphology observation and flow cytometry. Moreover, a DENV-infected ICR suckling mouse model was developed to investigate the protective role of TRQ in vivo. Results TRQ decreased the release of NO, IL6, TNFα and IL1B from BV2 cells and inhibited the activation of NLRP3. The presence of the NLRP3 agonist nigericin reversed the anti-inflammatory activities of TRQ. Furthermore, TRQ inhibited the death of HT22 cells by decreasing IL1B in DENV-infected BV2 cells. In addition, TRQ significantly attenuated weight loss, reduced clinical scores and extended the survival in DENV-infected ICR suckling mice. Critically, TRQ ameliorated pathological changes in ICR suckling mice brain by inhibiting microglia and NLRP3 activation and decreasing the production of inflammatory factors and the number of dead neurons. Conclusion TRQ exerts potent inhibitory effects on dengue encephalitis in vitro and in vivo by reducing DENV-2-induced microglial activation and subsequently decreasing the inflammatory response, thereby protecting neurons. These findings demonstrate the potential of TRQ in the treatment of dengue encephalitis.

Abstract The use of large language models (LLMs) in clinical medicine is currently thriving. Effectively transferring LLMs’ pertinent theoretical knowledge from computer science to their application in clinical medicine is crucial. Prompt engineering has shown potential as an effective method in this regard. To explore the application of prompt engineering in LLMs and to examine the reliability of LLMs, different styles of prompts were designed and used to ask different LLMs about their agreement with the American Academy of Orthopedic Surgeons (AAOS) osteoarthritis (OA) evidence-based guidelines. Each question was asked 5 times. We compared the consistency of the findings with guidelines across different evidence levels for different prompts and assessed the reliability of different prompts by asking the same question 5 times. gpt-4-Web with ROT prompting had the highest overall consistency (62.9%) and a significant performance for strong recommendations, with a total consistency of 77.5%. The reliability of the different LLMs for different prompts was not stable (Fleiss kappa ranged from −0.002 to 0.984). This study revealed that different prompts had variable effects across various models, and the gpt-4-Web with ROT prompt was the most consistent. An appropriate prompt could improve the accuracy of responses to professional medical questions.

Abstract Previous study showed that higher expression of prolactin (PRL) was found in CRPC samples compared with hormone-naive prostate cancer (HNPC) and benign prostatic hyperplasia (BPH) samples. We further investigate the function of PRL in prostate cancer (PCa) and explored its downstream effects. We found heterogeneous expression of the PRLR in clinical prostate samples. The VCaP and 22Rv1 cells exhibited PRLR expression. Among the downstream proteins, STAT5B was the dominant subtype in clinical samples and cell lines. Human recombinant PRL stimulation of PCa cells with PRLR expression resulted in increased phosphorylation of STAT5B(pSTAT5B) and progression of PCa in vitro and in vivo, and STAT5B knockdown can suppress the malignant behavior of PCa. To understand the mechanism further, we performed Bioinformatic analysis, ChIP qPCR, and luciferase reporter gene assay. The results revealed that ARRB2 was the transcription target gene of STAT5B, and higher expression of ARRB2 was related to higher aggression and poorer prognosis of PCa. Additionally, Gene set enrichment analysis indicated that higher expression of ARRB2 was significantly enriched in the MAPK signaling pathway. Immunohistochemistry (IHC) demonstrated elevated pSTAT5B, ARRB2, and pERK1/2 expression levels in CRPC tissues compared to HNPC and BPH. Mechanically, ARRB2 enhanced the activation of the MAPK pathway by binding to ERK1/2, thereby promoting the phosphorylation of ERK1/2 (pERK1/2). In conclusion, our study demonstrated that PRL stimulation can promote the progression of PCa through STAT5B/ARRB2 pathway and activation of MAPK signaling, which can be suppressed by intervention targeting STAT5B. Blockade of the STAT5B can be a potential therapeutic target for PCa.

Abstract The laboratory lightning test is essential for assessing the effectiveness of lightning strike protection (LSP). Particularly, direct lightning strike damage can be performed with pulsed current injection into the specimen. This paper focuses on the dynamic process of arc plasma and shock wave behaviour in the vicinity of the ‘strike’ point. A rod‐plate discharge load is built for testing aluminium and coated plate under 40‐kA‐level pulsed current. The visualisation of the luminous discharge plasma and its flow field via high‐speed photography (from different angles) is meticulously designed and implemented, synchronised with electro‐physical diagnostics. The results indicate some new mechanisms for lightning strike damage, apart from the impulse heat loading from the thermal arc. The transient current injection through the arc root concentrates on a thin skin layer (skin‐depth effect), with the radial‐attenuated current density, driving asynchronously electrical explosions on the plate surface. The inhomogeneous Joule heating of the plate leads to outwardly propagating phase transition and shock wave along the conductive surface. In addition, the electro‐thermal instability is observed and regarded as the seed of irregular erosion region. Spectroscopic information reveals two different plasma states of main discharge arc channel and adjacent surface electrical explosion. The correspondence of the physical mechanism of electrical explosion and optical radiation is established. Microscopic images for different regions depict erosion characteristics and summarise influencing factors, further confirming the mechanism above. The research clarifies the role of skin‐depth effect in transaction arc erosion for electrode, complements the electrical explosion theory with unevenly distributed current and helps optimise strategies of LSP.

The virulence of Mycobacterium tuberculosis (M. tuberculosis) is related to many factors, including intracellular survival, cell wall permeability, and cell envelope proteins. However, the biological function of the M. tuberculosis membrane protein Rv1476 remains unclear. To investigate the potential role played by Rv1476, we constructed an Rv1476 overexpression strain and found that overexpression of Rv1476 enhanced the intracellular survival of M. tuberculosis, while having no impact on the growth rate in vitro. Stress experiments demonstrated that the Rv1476 overexpression strain displayed increased susceptibility to different stresses compared to the wild-type strain. Transcriptome analysis showed that Rv1476 overexpression causes changes in the transcriptome of THP-1 cells, and differential genes are mainly enriched in cell proliferation, fatty acid degradation, cytokine–cytokine receptor interaction, and immune response pathways. Rv1476 overexpression inhibited the expression of some anti-tuberculosis-related genes, such as CCL1, IL15, IL16, ISG15, GBP5, IL23, ATG2A, IFNβ, and CSF3. Altogether, we conclude that Rv1476 may play a critical role for M. tuberculosis in macrophage survival.

Most state-of-the-art synthetic aperture radar (SAR) ship detection methods based on deep learning require large amounts of labeled data for network training. However, the annotation process requires significant manpower and resources especially for SAR images, since relevant background knowledge should be necessary for the annotators. Considering the available optical imagery datasets with labels, we propose an unsupervised oriented SAR ship detection method based on cross-modality distribution alignment, termed as CroMoDa. It consists of four components: 1) image-level feature alignment; 2) low-level feature despeckling; 3) cross-modality pseudo-label self-training; and 4) cross-modality object alignment. By aligning the multilevel feature distributions, modality-invariant features across the two imagery modalities can be learned. Considering speckle noise and other interferences in SAR images, the proposed loss term conducted on low-level features can enhance the object information to improve the detection accuracy. Moreover, the proposed pseudo-label self-training can better generate oriented SAR ship annotations than the other methods, which facilitates learning more discriminative features for SAR ship instances. With two optical–SAR dataset configurations, the proposed method is effectively evaluated by comparing to the other state of the arts, which demonstrates the great potential for SAR ship detection in real applications.

Abstract Extraretinal neovascularization is a hallmark of treatment-requiring retinopathy of prematurity (ROP). Optical coherence tomography angiography (OCTA) offers vascular flow and depth information not available from indirect ophthalmoscopy and structural OCT, but OCTA is only commercially available as a tabletop device. In this study, we used an investigational handheld OCTA device to study the vascular flow in and around retinal neovascularization in seven preterm infants with treatment-requiring ROP and contrasted them to images of vascular flow in six infants of similar age without neovascular ROP. We showed stages of retinal neovascularization visible in preterm infants from 32 to 47 weeks postmenstrual age: Intraretinal neovascularization did not break through the internal limiting membrane; Subclinical neovascular buds arose from retinal vasculature with active flow through the internal limiting membrane; Flat neovascularization in aggressive ROP assumed a low-lying configuration compared to elevated extraretinal neovascular plaques; Regressed neovascularization following treatment exhibited decreased vascular flow within the preretinal tissue, but flow persisted in segments of retinal vessels elevated from their original intraretinal location. These findings enable a pilot classification of retinal neovascularization in eyes with ROP using OCTA, and may be helpful in detailed monitoring of disease progression, treatment response and predicting reactivation.

Abstract Parkinson’s disease (PD) exhibits significant clinical heterogeneity, presenting challenges in the identification of reliable electroencephalogram (EEG) biomarkers. Machine learning techniques have been integrated with resting-state EEG for PD diagnosis, but their practicality is constrained by the interpretable features and the stochastic nature of resting-state EEG. The present study proposes a novel and interpretable deep learning model, graph signal processing-graph convolutional networks (GSP-GCNs), using event-related EEG data obtained from a specific task involving vocal pitch regulation for PD diagnosis. By incorporating both local and global information from single-hop and multi-hop networks, our proposed GSP-GCNs models achieved an averaged classification accuracy of 90.2%, exhibiting a significant improvement of 9.5% over other deep learning models. Moreover, the interpretability analysis revealed discriminative distributions of large-scale EEG networks and topographic map of microstate MS5 learned by our models, primarily located in the left ventral premotor cortex, superior temporal gyrus, and Broca’s area that are implicated in PD-related speech disorders, reflecting our GSP-GCN models’ ability to provide interpretable insights identifying distinctive EEG biomarkers from large-scale networks. These findings demonstrate the potential of interpretable deep learning models coupled with voice-related EEG signals for distinguishing PD patients from healthy controls with accuracy and elucidating the underlying neurobiological mechanisms.

As one branch of deterministic approaches to disjoint bilinear programming, cutting plane methods are renowned for its ability to systematically reduce the search space by adding cutting planes that are able to cut off regions deemed infeasible or suboptimal. Polar cuts have been widely utilized as a dominating type of cut in terms of deepness. During the establishment of a polar cut, the modified Newton's method is employed to derive the cutting points along the positive or negative extensions of edges emanating from a local solution. Nonetheless, its performance can be further improved along the positive extensions. Drawing inspiration from integer programming, we develop a new approach based on the LP duality theory for this purpose. It re-formulates the original program with a piece-wise linear concave objective function as a single LP. Moreover, we propose a new technique to derive the edges as accommodation to degeneracy. Numerical results show that, by utilizing our newly developed dual method, computing time can be gradually saved as the percentage of generated cutting points along the positive extensions of edges rises.

As the problem of information overload becomes more severe, it has become increasingly difficult for users to browse news that they are interested in. News recommendation is an effective method to alleviate this problem. In news recommendation, accurately obtaining rich semantic news representations and modeling user’s historical interests are long-standing challenges. Based on these two issues, we propose a News recommendation approach with Word-related joint Topic prediction(NWT). The core of our approach is the topic perceptron and the news encoder that emphasizes word relevance. The topic information and word relevance information are fused through joint training, enhancing the abilities of topic prediction and news representation. In the news encoder, we employ multi-head self-attention network to emphasize word relevance, capturing the semantic relationships between any two words in the news title and enhancing the representation of the news. In the topic perceptron, we use the enhanced word relevance-based news representation as input and learn the topic information in the news by assigning weights to different topics. During joint training, the overall news recommendation module obtains the news topic information. Additionally, the user encoder learns the user’s topic preferences and utilizes attention networks to highlight news articles that are more representative of the user’s interests, thereby acquiring a more accurate user representation. We conduct extensive experiments on the MIND dataset, and the results demonstrate that NWT outperforms most existing baseline methods across various evaluation metrics.

Coherent microwave radar utilizes the direct relationship between the orbital wave velocity and the wave height spectrum to retrieve wave parameters. However, due to the broken wave and its evolution, “Group-Line” is introduced in the radar-obtained wavenumber–frequency spectrum, and the dominant wave energy is reduced. Many methods have proposed to remove “Group-Line” in the wavenumber–frequency spectrum, but these methods can only remove low-frequency energy and fail to compensate for the dominant wave energy. To solve this problem, a method for wave parameter inversion using quasi-binary variational mode decomposition (QB-VMD) is proposed. First, QB-VMD decomposes the spatial–temporal radial velocity series, and a series of modes is obtained, including “Group-Line” and dominant wave modes. Second, the “Group-Line” mode is discarded, and the dominant wave mode is compensated appropriately to reconstruct the spatial–temporal radial velocity series. Finally, the wave parameters are retrieved according to the reconstructed spatial–temporal radial velocity series. The proposed method is verified by simulation. In addition, this article uses an eight-day dataset collected by the coherent $S$-band radar deployed at Beishuang island for analysis. The significant wave height and mean wave period are retrieved from the dataset. The wave parameters estimated by the proposed method are compared with the buoy results. The correlation coefficients are 0.97 and 0.80, and the root-mean-square errors are 0.12 m and 0.49 s, respectively. The results show that the proposed method can invert wave parameters using the coherent $S$-band radar with reasonable performance.

Hyperspectral target detection plays a pivotal role in various civil and military applications. Although recent advancements in deep learning have largely embraced supervised learning approaches, they often hindered by the limited availability of labeled data. Unsupervised learning, therefore, emerges as a promising alternative, yet its potential has not been fully realized in current methodologies. This article proposes an innovative unsupervised learning framework employing a momentum contrastive learning-based transformer network specifically tailored for hyperspectral target detection. The proposed approach innovatively combines transformer-based encoder and momentum encoder networks to enhance feature extraction capabilities, adeptly capturing both local spectral details and long-range spectral dependencies through the novel overlapping spectral patch embedding and a cross-token feedforward layer. This dual-encoder design significantly improves the model's ability to discern relevant spectral features amidst complex backgrounds. Through unsupervised momentum contrastive learning, a dynamically updated queue of negative sample features is utilized so that the model can demonstrate superior spectral discriminability. This is further bolstered by a unique background suppression mechanism leveraging nonlinear transformations of cosine similarity detection results, with two nonlinearly pull-up operations, significantly enhancing target detection sensitivity, where the nonlinearly operations are the exponential function with its normalization and the power function with its normalization, respectively. Comparative analysis against seven state-of-the-art hyperspectral target detection methods across four real hyperspectral images demonstrates the effectiveness of the proposed method for hyperspectral target detection, with an increase in detection accuracy and a competitive computational efficiency. An extensive ablation study further validates the critical components of the proposed framework, confirming its comprehensive capability and applicability in hyperspectral target detection scenarios.

Abstract Background Neoadjuvant immune checkpoint inhibitors(ICIs) combined with chemotherapy can improve non-small cell lung cancer(NSCLC) patients' pathological responses and show promising improvements in survival. Chronic obstructive pulmonary disease (COPD) is a systemic inflammatory disease, and its associated abnormal inflammatory response affects not only the immunotherapy efficacy but also immune-related adverse events. It remains unclear whether NSCLC patients with COPD can benefit from neoadjuvant ICIs combined with chemotherapy. Methods A retrospective observational clinical study was conducted on 105 consecutive NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy at the Department of Thoracic Surgery of Tianjin Chest Hospital between April 2020 and April 2023. Results A total of 74 NSCLC patients were included in the study, including 30 patients with COPD and 44 patients without COPD. The percentage of patients with a pathological complete response (PCR) was higher in the COPD group than in the non-COPD group (43.3% vs. 20.5%, P = 0.042). Multivariate logistic regression analysis of factors associated with PCR showed that the adjusted odds ratio (OR) was statistically significant for presence of COPD (OR = 3.020, 95%CI: 1.042–8.757; P = 0.042). Major pathological response (66.7% vs. 50%, P = 0.155), R0 resection rate (96.7% vs.93.2%, P = 0.642), N2 lymph node downstaging(92.3% vs. 66.7%, P = 0.182) and objective response rate (70% vs. 63.6%, P = 0.57) were not significantly different between the groups. Progression-free survival(PFS) was not reached in the COPD group and 17 months (95%CI: 12.1–21.9) in the non-COPD group, with statistically significance (χ2 = 6.247, P = 0.012). Multivariate Cox’s regression analysis showed that the adjusted hazard ratio (HRadj) was statistically significant for presence of COPD (HRadj = 0.321, 95%CI: 0.111–0.930; P = 0.036). The grade 3 and grade 4 adverse events in the COPD group were leukopenia (3.3%, 6.7%), neutropenia (3.3%, 6.7%), fatigue (6.7%, 0%), gastrointestinal reactions (3.3%, 0%), and hypothyroidism (3.3%, 0%). In the non-COPD group, the corresponding adverse events were leukopenia (6.8%, 6.8%), neutropenia (3.3%, 6.8%), fatigue (2.3%, 0%), gastrointestinal reactions (2.3%, 0%), and hypothyroidism (2.3%, 0%), respectively. Conclusions The present study indicates that the presence of COPD may improve PCR, prolong PFS, and have an acceptable safety profile in NSCLC patients receiving neoadjuvant ICIs combined with chemotherapy.

Abstract Patients with residual nasopharyngeal carcinoma after receiving definitive treatment have poor prognoses. Although immune checkpoint therapies have achieved breakthroughs for treating recurrent and metastatic nasopharyngeal carcinoma, none of these strategies have been assessed for treating residual nasopharyngeal carcinoma. In this single-arm, phase 2 trial, we aimed to evaluate the antitumor efficacy and safety of toripalimab (anti-PD1 antibody) plus capecitabine in patients with residual nasopharyngeal carcinoma after definitive treatment (ChiCTR1900023710). Primary endpoint of this trial was the objective response rate assessed according to RECIST (version 1.1). Secondary endpoints included complete response rate, disease control rate, duration of response, progression-free survival, safety profile, and treatment compliance. Between June 1, 2020, and May 31, 2021, 23 patients were recruited and received six cycles of toripalimab plus capecitabine every 3 weeks. In efficacy analyses, 13 patients (56.5%) had complete response, and 9 patients (39.1%) had partial response, with an objective response rate of 95.7% (95% CI 78.1-99.9). The trial met its prespecified primary endpoint. In safety analyses, 21 of (91.3%) 23 patients had treatment-related adverse events. The most frequently reported adverse event was hand-foot syndrome (11 patients [47.8%]). The most common grade 3 adverse event was hand-foot syndrome (two patients [8.7%]). No grades 4-5 treatment-related adverse events were recorded. This phase 2 trial shows that combining toripalimab with capecitabine has promising antitumour activity and a manageable safety profile for patients with residual nasopharyngeal carcinoma.

Abstract Owing to the emergence and rapid advances of new-generation information and digitalization technologies, the concept of model-driven digital twin has received widespread attentions and is developing vigorously. Driven by data and simulators, the digital twin can create the virtual twins of physical objects to perform monitoring, simulation, prediction, optimization, and so on. Hence, the application of digital twin can increase efficiency and security of systems by providing reliable model and decision supports. In this paper, we propose a state-aware model learning method to simulate and analyze the lightweight protocol implementations in edge/cloud environments. We introduce the data flow of program execution and network interaction inputs/outputs (I/O) into the extended finite state machine (EFSM) to expand the modeling scope and insight. We aim to calibrate the states and construct an accurate state-machine model using a digital twin based layered approach to reasonably reflect the correlation of a device’s external behavior and internal data. This, in turn, improves our ability to verify the logic and evaluate the security for protocol implementations. This method firstly involves instrumenting the target device to monitor variable activity during its execution. We then employ learning algorithms to produce multiple rounds of message queries. Both the I/O data corresponding to these query sequences and the state calibration information derived from filtered memory variables are obtained through the mapper and execution monitor, respectively. These two aspects of information are combined to dynamically and incrementally construct the protocol’s state machine. We apply this method to develop SALearn and evaluate the effectiveness of SALearn on two lightweight protocol implementations. Our experimental results indicate that SALearn outperforms existing protocol model learning tools, achieving higher learning efficiency and uncovering more interesting states and security issues. In total, we identified two violation scenarios of rekey logic. These situations also reflect the differences in details between different implementations.

Background: Arthrofibrosis (AF) is a fibrotic joint disease resulting from excessive collagen production and fibrous scar formation after total knee arthroplasty (TKA). This devastating complication may cause consistent pain and dramatically reduction of functionality. Unfortunately, the conservative treatments to prevent the AF in the early stage are largely unknown due to the lack of specific biomarkers and reliable therapeutic targets. Methods: In this study, we extracted1782 fibrosis related genes (FRGs) from 373,461published literature based on the large natural language processing models (ChatGPT) and intersected with the 2750 differential expressed genes (DEGs) from mRNA microarray (GSE135854). A total of 311 potential AF biomarker genes (PABGs) were obtained and functional analysis were performed including gene ontology (GO) annotation and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses. Subsequently, we accomplished validation in AF animal models with immobilization of the unilateral knee joints of 16 rabbits for 1-week, 2-weeks, 3-weeks and 4-weeks. Finally, we tested the biomarkers in a retrospective cohort enrolled 35 AF patients and 35 control group patients. Results: We identified G-protein-coupled receptor 17 (GPR17) as a reliable therapeutic biomarker for AF diagnosis with higher AUC (0.819) in the ROC curve. A total of 21 potential drugs targeted to GPR17 were screened. Among them, pranlukast and montelukast have achieved therapeutic effect in animal models. In addition, we established an online AF database for data integration (https://chenxi2023.shinyapps.io/afdbv1). Conclusions: These results unveiling therapeutic biomarkers for AF diagnosis, and provide potential drugs for clinical treatment. The translational potential of this article: Our study demonstrated that GPR17 holds significant promise as a potential biomarker and therapeutic target for arthrofibrosis. Moreover, pranlukast and montelukast targeted to GPR17 that could be instrumental in the treatment of AF.

Abstract The cGAS-STING signaling pathway has emerged as a critical mediator of innate immune responses, playing a crucial role in improving antitumor immunity through immune effector responses. Targeting the cGAS-STING pathway holds promise for overcoming immunosuppressive tumor microenvironments (TME) and promoting effective tumor elimination. However, systemic administration of current STING agonists faces challenges related to low bioavailability and potential adverse effects, thus limiting their clinical applicability. Recently, nanotechnology-based strategies have been developed to modulate TMEs for robust immunotherapeutic responses. The encapsulation and delivery of STING agonists within nanoparticles (STING-NPs) present an attractive avenue for antitumor immunotherapy. This review explores a range of nanoparticles designed to encapsulate STING agonists, highlighting their benefits, including favorable biocompatibility, improved tumor penetration, and efficient intracellular delivery of STING agonists. The review also summarizes the immunomodulatory impacts of STING-NPs on the TME, including enhanced secretion of pro-inflammatory cytokines and chemokines, dendritic cell activation, cytotoxic T cell priming, macrophage re-education, and vasculature normalization. Furthermore, the review offers insights into co-delivered nanoplatforms involving STING agonists alongside antitumor agents such as chemotherapeutic compounds, immune checkpoint inhibitors, antigen peptides, and other immune adjuvants. These platforms demonstrate remarkable versatility in inducing immunogenic responses within the TME, ultimately amplifying the potential for antitumor immunotherapy.

Abstract Background China has the third-largest burden of tuberculosis (TB) cases in the world with great challenges towards ending TB. Primary health care (PHC) sectors play a critical role in TB prevention and control in communities under the Chinese integrated TB control model. However, there is a lack of comprehensive review of research evidence on TB control in PHC sectors under the integrated TB control model in China. Methods This review was conducted following the PRISMA guidelines. Articles published from 2012 to January 2022 were searched from four international and three Chinese databases. Studies conducted inside mainland China and relevant with TB control service in PHC sectors under the integrated model were included. After study selection, data extraction, and quality assessment, the meta-analysis was performed with RevMan using a random-effect model.When I2 was more than 50%, subgroup analysis was performed to explore possible reasons for heterogeneity. We also conducted a post hoc sensitivity analysis for outcomes after meta-analysis by exclusion of studies with a high risk of bias or classified as low quality. Results Forty-three studies from 16 provinces/municipalities in China were included in this review, and most studies included were of medium quality. PHC sectors in East China delivered TB control service better overall than that in West China, especially in tracing of patients and TB case management (TCM). In meta-analyses, both the pooled arrival rate of tracing and pooled TCM rate in East China were higher than those in West China. TB patients had a low degree of willingness to receive TCM provided by healthcare workers in PHC sectors nationwide, especially among migrant TB patients. There were 9 studies reporting factors related to TB control service in PHC sectors, 6 (2 in East and 4 in West China) of which indentified several characteristics of patients as associated factors. The context of PHC sectors was demonstrated to influence delivery of TB control service in PHC sectors in 5 studies (3 in East, 1 in Middle and 1 in West China). Most studies on strategies to promoting TB control services in PHC sectors were conducted in East China and some of these studies identified several online and offline interventions and strategies improving patients’ treatment compliance [pooled OR (95% CI): 7.81 (3.08, 19.19] and awareness of TB [pooled OR (95% CI): 6.86 (2.16, 21.72)]. Conclusion It is of urgent need to improve TB control in PHC sector in China, particularly in West China. Formative and implementation research with rigorous design are necessary to develop comprehensive, context-specific, and patient-centered TB control strategies to promote ending TB in China.

Recent studies have demonstrated that neuroplasticity, such as synaptic plasticity and neurogenesis, exists throughout the normal lifespan but declines with age and is significantly impaired in individuals with Alzheimer’s disease. Hence, promoting neuroplasticity may represent an effective strategy with which Alzheimer’s disease can be alleviated. Due to their significant ability to self-renew, differentiate, and migrate, neural stem cells play an essential role in reversing synaptic and neuronal damage, reducing the pathology of Alzheimer’s disease, including amyloid-β, tau protein, and neuroinflammation, and secreting neurotrophic factors and growth factors that are related to plasticity. These events can promote synaptic plasticity and neurogenesis to repair the microenvironment of the mammalian brain. Consequently, neural stem cells are considered to represent a potential regenerative therapy with which to improve Alzheimer’s disease and other neurodegenerative diseases. In this review, we discuss how neural stem cells regulate neuroplasticity and optimize their effects to enhance their potential for treating Alzheimer’s disease in the clinic.

The dichotomized brain system is a concept that was generalized from the ‘dual syndrome hypothesis’ to explain the heterogeneity of cognitive impairment, in which anterior and posterior brain systems are independent but partially overlap. The dopaminergic system acts on the anterior brain and is responsible for executive function, working memory, and planning. In contrast, the cholinergic system acts on the posterior brain and is responsible for semantic fluency and visuospatial function. Evidence from dopaminergic/cholinergic imaging or functional neuroimaging has shed significant insight relating to the involvement of the cerebellum in the cognitive process of patients with Parkinson’s disease. Previous research has reported evidence that the cerebellum receives both dopaminergic and cholinergic projections. However, whether these two neurotransmitter systems are associated with cognitive function has yet to be fully elucidated. Furthermore, the precise role of the cerebellum in patients with Parkinson’s disease and cognitive impairment remains unclear. Therefore, in this review, we summarize the cerebellar dopaminergic and cholinergic projections and their relationships with cognition, as reported by previous studies, and investigated the role of the cerebellum in patients with Parkinson’s disease and cognitive impairment, as determined by functional neuroimaging. Our findings will help us to understand the role of the cerebellum in the mechanisms underlying cognitive impairment in Parkinson’s disease.

With the growth of global communication demand, the spaceborne core network can not only reduce frequent signaling interactions between satellites and the ground, but also break through the constraints of geographical regions, providing strong support for the integrated network architecture of heaven and earth and global communication operations.However, due to the resource limitations of satellites and the dynamic and time-varying topology of satellite internet on a large scale, the deployment of traditional core network elements in spaceborne environments has encountered significant challenges.This article is dedicated to studying the challenges of lightweight, flexible deployment, and low latency in onboard core networks, aiming to explore new design strategies for onboard lightweight core networks and provide a solid theoretical foundation for global communication operations.Multiple lightweight strategies, including minimum network element set deployment, single network element function tailoring, interface protocol lightweight, network element fusion and reconstruction, platform architecture lightweight, and transmission protocol reconstruction were firstly studied.Then, detailed simulation experiments were conducted on the selected strategies, and the experimental results confirmed that the lightweight processing of the spaceborne core network has superior performance in resource allocation and signaling process.

To address the problems of strain localization, the exact Mohr-Coulomb (MC) model is used based on second-order cone programming (mpcFEM-SOCP) in the framework of micropolar continuum finite element method. Using the uniaxial compression test, we focused on the earth pressure problem of rigid wall segment involving non-associated plasticity. The numerical results reveal that when mpcFEM-SOCP is applied, the problems of mesh dependency can be effectively addressed. For geotechnical strain localization analysis involving non-associated MC plasticity, mpcFEM-SOCP in conjunction with the pseudo-time discrete scheme can improve the numerical stability and avoid the unreasonable softening issue in the pressure-displacement curves, which may be encountered in the conventional FEM. It also shows that the pressure-displacement responses calculated by mpcFEM-SOCP with the pseudo-time discrete scheme are higher than those calculated by mpcFEM-SOCP with the Davis scheme. The inclination angle of shear band predicted by mpcFEM-SOCP with the pseudo-time discrete scheme agrees well with the theoretical solution of non-associated MC plasticity.

Abstract Background Up to the present time, there has remained a lack of strong evidence as to whether sentinel lymph node biopsy can replace lymphadenectomy for early endometrial cancer. The traditional surgery for endometrial cancer includes pelvic lymphadenectomy and paraaortic lymph node resection, but complications often seriously affect patients’ quality of life. Two randomized controlled trials with large samples have proved that lymphadenectomy does not improve the overall recurrence rate and survival rate of patients. On the contrary, it increases the incidence of complications and even mortality. The current trial is designed to clarify whether sentinel lymph node biopsy can replace lymphadenectomy for early endometrial cancer patients with negative lymph nodes. Methods This study is a randomized, open-label, multicenter and non-inferiority controlled clinical trial in China. Potential participants will be patients with pathologically confirmed endometrial cancer at the Zhejiang Cancer Hospital, Jiaxing Maternity and Child Health Care Hospital, and the First Hospital of Jiaxing in China. The total sample size for this study is 722. Patients will be randomly assigned in a 1:1 ratio to two groups. Patients in one group will undergo sentinel lymph node biopsy + total hysterectomy + bilateral salpingo-oophorectomy ± paraaortic lymph node resection. Patients in the other group will undergo sentinel lymph node biopsy + total hysterectomy + bilateral salpingo-oophorectomy + pelvic lymphadenectomy ± paraaortic lymph node resection. The 3-year disease-free survival rate, overall survival rate, quality of life (use EORTC QLQ-C30 + QLQ-CX24), and perioperative related indexes of the two groups will be compared. Results We expect to find that for patients with early endometrial cancer, the 3-year disease-free survival rate following sentinel lymph node biopsy with indocyanine green combined with near-infrared fluorescence imaging is similar to that following lymphadenectomy. The operation time, as well as incidence of pelvic lymphocyst, lymphedema of lower limb, and edema of vulva in patients who only undergo sentinel lymph node biopsy are expected to be significantly lower than in patients who undergo lymphadenectomy. The quality of life of patients who undergo sentinel lymph node biopsy alone will be significantly better than that of patients who undergo lymph node dissection. Conclusion This will prove that the prognosis of sentinel lymph node biopsy alone with indocyanine green combined with near-infrared fluorescence imaging is not inferior to that of sentinel lymph node biopsy plus lymphadenectomy for early stage endometrial cancer with negative nodal assessment intraoperatively. In addition, sentinel lymph node biopsy alone with indocyanine green combined with near-infrared fluorescence imaging results in fewer surgical complications and gives patients better quality of life. Trial registration chictr.org.cn, ChiCTR1900023161. Registered 14 May 2019, http://www.chictr.org.cn/edit.aspx?pid=38659&htm=4 .

Abstract Purpose To explore the efficacy of different approaches of seminal vesiculoscopy surgery and the predictive factors of good treatment outcome. Materials and Methods A retrospective analysis of 68 patients who underwent seminal vesiculoscopy for hematospermia in our hospital from January 2015 to January 2021. According to different surgical approaches, they were divided into three groups: natural ejaculatory ducts (method A, 45 cases), assisted transurethral resection/incision of ejaculatory ducts (method B, 14 cases), fenestration in prostatic utricle (method C, 9 cases). We analyzed the recurrence rate of the three surgical approaches and the predictive factors of treatment efficacy. Results The total recurrence rate after the seminal vesiculoscopy for hematospermia in this group was 32.35%. The postoperative recurrence rates of the three methods were 24.44% for method A, 50.00% for method B and 44.44% for method C, and there was no significant difference among the three methods (P > 0.05). The data of five predictors of 45 cases in method A group were included in the Univariate Logistic analysis, the results suggest that whether complicated with seminal tract stones/cysts was an effective predictor (OR 0.250, P = 0.022), which was still an effective predictor in the Multivariate Logistic analysis model (OR 0.244, P = 0.010). Conclusions The Transurethral seminal vesiculoscopy technique demonstrates a low postoperative recurrence rate in treating hematospermia. Among the various approaches, the intraoperative use of natural orifices through the ejaculatory duct exhibits the lowest recurrence rate. Additionally, seminal tract stones/cysts effectively predict favorable postoperative outcomes.

Abstract Senescent microglia are a distinct microglial phenotype present in aging brain that have been implicated in the progression of aging and age-related neurodegenerative diseases. However, the specific mechanisms that trigger microglial senescence are largely unknown. Quinolinic acid (QA) is a cytotoxic metabolite produced upon abnormal activation of microglia. Brain aging and age-related neurodegenerative diseases have an elevated concentration of QA. In the present study, we investigated whether QA promotes aging and aging-related phenotypes in microglia and C. elegans. Here, we demonstrate for the first time that QA, secreted by abnormal microglial stimulation, induces impaired mitophagy by inhibiting mitolysosome formation and consequently promotes the accumulation of damaged mitochondria due to reduced mitochondrial turnover in microglial cells. Defective mitophagy caused by QA drives microglial senescence and poor healthspan in C. elegans. Moreover, oxidative stress can mediate QA-induced mitophagy impairment and senescence in microglial cells. Importantly, we found that restoration of mitophagy by mitophagy inducer, urolithin A, prevents microglial senescence and improves healthspan in C. elegans by promoting mitolysosome formation and rescuing mitochondrial turnover inhibited by QA. Thus, our study indicates that mitolysosome formation impaired by QA is a significant aetiology underlying aging-associated changes. QA-induced mitophagy impairment plays a critical role in neuroinflammation and age-related diseases. Further, our study suggests that mitophagy inducers such as urolithin A may offer a promising anti-aging strategy for the prevention and treatment of neuroinflammation-associated brain aging diseases.

Abstract Despite the initial successes of the Bacillus Calmette-Guerin (BCG) vaccine in children, its efficacy against tuberculosis is highly variable. There is a lack of understanding about how mental conditions influence BCG vaccination. Here, we used the chronic social defeat stress (CSDS) model to explore the effects of depression on BCG vaccination efficacy. We observed higher lung and spleen bacterial loads and a lower organ index in depressed compared to BCG mice. Meanwhile, a relatively lower T cell protective efficacy was observed in both compared to control and BCG mice via a mycobacterium growth inhibition assay (MGIA). Cytokine expression of IL-12p40, IL-1β, IL-17, TNF-α and IFN-γ was reduced, whereas the expression of IL-10 and IL-5 was increased in the spleen of both compared to BCG mice. Moreover, the proportions of CD4+IFN-γ+, CD8+IFN-γ+ T lymphocytes and CD4+ effector/central memory T cells were reduced in the splenocytes of the depressed BCG mice. Depression promotes CD4+ regulatory T cells (Treg) and myeloid-derived suppressor cell (MDSC) generation in depressed mice, contributing to the reduced pro-inflammatory immune response upon BCG vaccination. This study provides insight into the decreased protective immunity by BCG vaccination attributable to depression in mice.

Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version — T2T-CHM13 — reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploids. The quality of T2T-YAO is much better than those of all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, an accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

Abstract Background When influenza A‐related pneumonia is complicated by bacteria, aspergillus, and other infections, the disease is aggravated, while there is no research on the role of Epstein–Barr virus (EBV) on patients with influenza A‐related pneumonia. This study aimed to evaluate the relationship between the isolation of EBV and influenza A‐related pneumonia. Methods This is a clinical study based on the baseline data of a retrospective cohort. A total of 113 cases of influenza A‐related pneumonia who underwent polymerase chain reaction test for isolation of EBV‐DNA in lower respiratory tract specimens during six influenza seasons from 2013–2014 to 2018–2019 were enrolled. According to the results of EBV‐DNA, patients were divided into EBV‐positive group and EBV‐negative group, and the role of EBV‐DNA on patients with influenza A‐related pneumonia was analyzed. Regression analysis was used to explore the potential risk factors for the development of moderate‐to‐severe acute respiratory distress syndrome (ARDS) in patients with influenza A‐related pneumonia during hospitalization. Results Among 113 patients with influenza A‐related pneumonia, there were 53 patients with EBV‐positive and 60 patients with EBV‐negative. The EBV‐positive group had higher intensive care unit admission rate, hospital stay, invasive mechanical ventilation rate, extracorporeal membrane oxygenation rate, Sequential Organ Failure Assessment (SOFA) score, and moderate‐to‐severe ARDS rate. Patients were divided into severe group and mild group. Patients in severe group had lower lymphocyte count, platelet count, and albumin level, while the levels of aspartate aminotransferase, alanine transaminase, creatine kinase, lactic dehydrogenase, and total bilirubin were higher in severe group. The levels of D‐dimer, serum ferritin, C‐reactive protein, and procalcitonin were higher in severe group than those in the mild group. Multivariate logistic regression analysis revealed that the isolation of EBV (odds ratio = 2.713, 95% confidence interval: 1.094–6.729, P = 0.031) and lymphocyte count (odds ratio = 3.585, 95% confidence interval: 1.157–11.101, P = 0.027) were independent risk factors for moderate‐to‐severe ARDS in patients with influenza A‐related pneumonia. Conclusion The isolation rate of EBV in the lower respiratory tract was 46.9%. The length of hospital stays, intensive care unit admission rate, invasive mechanical ventilation rate, extracorporeal membrane oxygenation rate, SOFA score, and the proportion of moderate‐to‐severe ARDS in the EBV‐positive group were higher than those in the EBV‐negative group, while there was no effect on the death during hospitalization. The isolation of EBV in the lower respiratory tract and low lymphocyte count are independent risk factors for the development of moderate‐to‐severe ARDS in patients with influenza A‐related pneumonia.

Abstract Background Cardiac remodeling is the initiating factor for the development of heart failure, which can result from various cardiomyopathies. Cytochrome c oxidase subunit 6A2 (COX6A2) is one of the components of cytochrome c oxidase that drives oxidative phosphorylation. The pathogenesis of myocardial remodeling caused by COX6A2 deficiency in humans remains unclear because there are no suitable research models. In this study, we established a COX6A2-deficient human cardiac myocyte (CM) model that mimics the human COX6A2 homozygous mutation and determined the effects of COX6A2 dysfunction and its underlying mechanism. Methods A human COX6A2 homozygous knockout cardiomyocyte model was established by combining CRISPR/Cas9 gene editing technology and hiPSC-directed differentiation technology. Cell model phenotypic assays were done to characterize the pathological features of the resulting COX6A2-deficient cardiomyocytes. Results COX6A2 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a COX6A2 gene knockout showed abnormal energy metabolism, increased oxidative stress levels, abnormal calcium transport activity, and decreased contractility. In addition, L-carnitine and trimetazidine significantly improved energy metabolism in the COX6A2-deficient human myocardial model. Conclusions We have established a COX6A2-deficient human cardiomyocyte model that exhibits abnormal energy metabolism, elevated oxidative stress levels, abnormal calcium transport, and reduced contractility. This model represents an important tool to gain insight into the mechanism of action of energy metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of COX6A2 deficiency, and facilitate drug screening.

Abstract The water–cement/binder ratio and the admixture of water-reducing agents strongly affect the rheological properties of cement pastes. This study develops mathematical models to predict the apparent viscosity of cement pastes with varying water-cement/binder ratios and polycarboxylate-based superplasticizer content by introducing the power law shear stress-shear strain relation of non-Newtonian fluids into the Navier–Stokes motion equations. The developed models are compared with the results of rheological experiments and verified for their accuracy in simulating the apparent viscosity of cement pastes. These models provide insight into the rheological behaviour of cement pastes and could have practical applications in the construction industry.

Abstract Ammonia (NH3) is the second-most produced chemical with broad applications and vital for the chemical industry. However, the current Haber–Bosch synthesis is problematic with high energy consumption and carbon footprints. Electrochemical nitrate reduction (NO3RR) to produce NH3 is a green, low-carbon and efficient alternative route to simultaneously benefit wastewater treatment, mild NH3 production and global warming mitigation. Compared to noble metal catalysts or the nanosized counterparts, iron single-atom catalysts (Fe SACs) boast unique advantages to promote the NO3RR because of the exceptional selectivity, inexpensiveness, high efficiency and good durability. Due to the rapid development of the emerging field, a timely Perspective with an emphasis on the recent advances in Fe SACs-catalyzed NO3RR is currently lacking. The Perspective aims to give an account of the up-to-date progresses on Fe SACs-promoted NO3RR for NH3 production. The catalyst design, characterizations, mechanism studies, etc. will be illustrated, and lastly the challenges and outlook will be discussed to provide insights for future studies.

Abstract Background Brain metastases (BMs) are the most frequent intracranial tumours associated with poor clinical outcomes. Radiotherapy is essential in the treatment of these tumours, although the optimal radiation strategy remains controversial. The present study aimed to assess whether whole brain radiation therapy with a simultaneous integrated boost (WBRT + SIB) provides any therapeutic benefit over WBRT alone. Methods We included and retrospectively analysed 82 patients who received WBRT + SIB and 83 who received WBRT alone between January 2012 and June 2021. Intracranial progression-free survival (PFS), local tumour control (LTC), overall survival (OS), and toxicity were compared between the groups. Results Compared to WBRT alone, WBRT + SIB improved intracranial LTC and PFS, especially in the lung cancer subgroup. Patients with high graded prognostic assessment score or well-controlled extracranial disease receiving WBRT + SIB had improved intracranial PFS and LTC. Moreover, WBRT + SIB also improved the long-term intracranial tumour control of small cell lung cancer patients. When evaluating toxicity, we found that WBRT + SIB might slightly increase the risk of radiation-induced brain injury, and that the risk increased with increasing dosage. However, low-dose WBRT + SIB had a tolerable radiation-induced brain injury risk, which was lower than that in the high-dose group, while it was comparable to that in the WBRT group. Conclusions WBRT + SIB can be an efficient therapeutic option for patients with BMs, and is associated with improved intracranial LTC and PFS. Furthermore, low-dose WBRT + SIB (biologically effective dose [BED] ≤ 56 Gy) was recommended, based on the acceptable risk of radiation-induced brain injury and satisfactory tumour control. Trial registration Retrospectively registered.

Abstract Background Intimate Partner Violence (IPV) is prevalent among HIV-infected men who have sex with men (MSM), with well-established risk factors and adverse outcomes. However, there is a lack of comprehensive investigation of both upstream risk factors and downstream adverse outcomes among HIV-infected MSM in a Chinese context. This study aimed to examine IPV and its associations among a Chinese sample of HIV-infected MSM. Methods A cross-sectional study was conducted among 294 HIV-infected MSM in Jinan City from June to December 2020. All data were collected through an online questionnaire, which included IPV, sexual risk behavior, antiretroviral therapy (ART) adherence, depression, anxiety, and suicidal ideation. Chi-square tests and multivariate logistic regressions were performed to examine risk factors and adverse outcomes of IPV. Results Of the 294 HIV-infected MSM, 71.1% experienced any IPV, including control (37.1%), threat of public identity (30.6%), emotional violence (25.2%), security threat (18.4%), and physical violence (13.9%). The prevalence of sexual risk behavior, good ART adherence, depression, anxiety, and suicidal ideation was 55.1%, 53.4%, 48.3%, 32.3%, and 65.0%, respectively. Abuse of methamphetamine (METH) (aOR:2.79; 95%CI:1.43 ~ 5.45), capsule 0 or stimulating liquid (aOR:2.68; 95%CI:1.31 ~ 5.47), Magu (aOR:3.16; 95%CI:1.51 ~ 6.60), and other new drugs (aOR:2.87; 95%CI:1.52 ~ 5.43), disclosing HIV infection to partners (aOR:2.03; 95%CI:1.10 ~ 3.78), and gay sexual orientation (aOR = 3.32; 95%CI: 1.82 ~ 6.05) were significantly correlated with the experience of IPV. In addition, IPV was significantly associated with sexual risk behavior (aOR = 2.02; 95%CI:1.16 ~ 3.53), ART adherence (aOR = 2.63; 95%CI:1.46 ~ 4.74), depression (aOR = 3.83; 95%CI:2.09 ~ 7.02), anxiety (aOR = 2.27; 95%CI:1.19 ~ 4.35), and suicidal ideation (aOR = 3.78; 95%CI:2.11 ~ 6.80). Conclusions IPV is prevalent among HIV-infected MSM and is associated with poor behavioral and mental health, highlighting more efforts are needed to address this issue. The finding that new drug abuse, HIV disclosure, and gay sexual orientation are associated with increased risk of IPV provides essential insights for the development of comprehensive and targeted IPV prevention and intervention programs in the future.

Abstract This study aimed to evaluate the guiding role of left adrenal vein (LAV) for right adrenal venous sampling (AVS). A total of 347 patients who were diagnosed with primary aldosteronism (PA) and underwent successful AVS procedures from January 2020 to July 2021 were retrospectively analyzed. According to the different quadrant position of the orifice of right adrenal vein (RAV), the area where the orifice of RAV is located is divided into three areas: A, B, and C and the area A is further subdivided into A1, A2, and A3 areas. By counting the area where the orifice of RAV is located, the guiding role of the LAV on the RAV is determined. Most of the orifice of RAV are located in area A, and the proportions of areas A, B, and C was 96.8%, 1.4%, and 1.7%, respectively. In area A, areas A1, A2, and A3 account for 80.9%, 17.0%, and 2.1%, respectively. High body mass index, female and smaller the angle between the LAV and horizontal line was associated with the closer positional relationship between the LAV on the RAV. These findings suggest that most of the horizontal position of the RAV orifice is close to the horizontal position of the most distal end of the LAV, which indicate that the LAV location can play an important role on the guiding for right AVS. Additionally, body mass index, sex, and the angle of the LAV was largely related to location of the orifice of the RAV.