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Abstract Background The impact of diabetes on the risk of Alzheimer’s disease remains uncertain. This study aimed to explore this issue from multiple perspectives by using the Mendelian randomization (MR) approach. Methods Instrumental variables for predicting six diabetic traits (including insulin and blood glucose), eight metabolic risk factors for diabetes (including total cholesterol and blood pressure), and seven diabetic genes were extracted from their summary data. These data were derived from multiple European cohorts and included 31,684 to 810,865 subjects respectively. The two-sample MR, multivariate MR, and summary-data-based Mendelian randomization (SMR) methods were employed to determine the associations of these traits or genes with the risk of Alzheimer’s disease. Results The two-sample MR showed that elevated fasting insulin and total cholesterol levels were associated with an increased risk of dementia in Alzheimer’s disease (P = 0.022, P = 0.041). Elevated systolic and diastolic blood pressure levels were associated with a decreased risk of dementia in Alzheimer’s disease (P = 0.036, P = 0.025). The multivariate MR reported that adjusting for telomere length (a well-established biomarker of aging) did not change these findings (P

IntroductionThe extensively used Lindera communis Hemsl. (Lauraceae) in traditional Chinese medicine has been specifically employed for wound healing and treating skin diseases in cattle and horses, suggesting its potential antibacterial properties. To explore the antibacterial activities of L. communis plants, we investigated the chemicals, antibacterial activities and wound healing and of the n-hexane fraction of L. communis roots (LCH).MethodsOur study included detecting phytochemical constituents, determining minimum inhibitory concentration (MIC) for different extract fractions, analyzing growth curves, assessing membrane integrity, monitoring potential changes in the membrane using scanning electron microscopy, and evaluating wound healing in rat excisional wounds.ResultsBased on our findings, humulene-type sesquiterpenes, guaiane-type sesquiterpenes, and lauric acid were identified from the LCH, responsible for antibacterial and wound healing activities. The results are that LCH affected the growth of methicillin-resistant Staphylococcus aureus (MIC: 0.1 mg/mL) through morphological alterations and disrupting cell surface structures, causing membrane hyperpolarization and altering membrane integrity. This result was subsequently validated through SEM analysis and cytotoxicity against HaCaT cells (IC50 1.83 ± 0.21 mg/mL). LCH also has exhibited remarkable effectiveness in healing rat excisional wounds, reinforcing its traditional use as a wound-healing agent.DiscussionThe findings substantiate the scientific essence of traditional applications, while also exhibiting significant potential as a promising candidate for the development of innovative and readily accessible wound healing agents.

Co-infection with human immunodeficiency virus (HIV) significantly increases the incidence of human papillomavirus (HPV) infection and HPV-related cancers among men who have sex with men (MSM). Conversely, HPV infection can also influence HIV acquisition rates. HIV-induced immune suppression may affect chromosomal stability, gene expression, protein function and other molecular components in MSM with HPV-related cancers. Additionally, HIV infection also alters cellular mechanisms by compromising immune responses and epithelial integrity. In this review, we reviewed the influence of HIV on specific HPV-related cancers in MSM, including oropharyngeal squamous cell carcinoma, penile cancer, and anal cancer. We integrated epidemiological data from the past five years and discussed diagnosis and treatment strategies. Overall, our review offers crucial insights into the underlying molecular and cellular mechanisms of these co-infection MSM patients. Our review aims to assist future research in developing effective treatment strategies for MSM with HIV/HPV co-infection.

Objectives: Recent mpox outbreaks highlight diverse transmission modes, with sexual behavior prominent in China's IIb strain. Nevertheless, despite HPV being a common sexually transmitted pathogen, there is a paucity of research into its coexistence and genotype distribution within this patients population. Methods: We conducted a study at the Third People's Hospital of Shenzhen from May to September 2023. We collected information on mpox patients, including their sociodemographic and clinical characteristics. Anal swabs were collected for HPV genotyping. Results: Among 73 MSM mpox cases, HIV positivity was 56.2 % (41/73) and HPV positivity 80.4 % (41/51). Multiple HPV infections were prevalent (56.9 %, 29/51), especially among HIV-positive (93 %, 27/29). HPV16 (29.3 %, 12/41) was the most common high-risk genotype, followed by HPV59 (26.8 %, 10/41), HPV42 (19.5 %, 8/41), HPV6 (14.6 %, 6/41), and HPV54 (14.6 %, 6/41). HPV infection was significantly associated with HIV infection (p = 0.001). Additionally, HIV infection (p = 0.001) and PCR-detected positive sites for mpox (p = 0.047) were associated with high-risk HPV infection. Conclusions: In this study, most of the mpox patients were found to be infected with HPV, mostly with high-risk types and multiple infections. Therefore, it is strongly recommended that mpox-infected individuals intensify HPV-related screening, prevention, and treatment measures.

Abstract Phylogenetic trees represent the evolutionary relationships and ancestry of various species or groups of organisms. Comparing these trees by measuring the distance between them is essential for applications such as tree clustering and the Tree of Life project. Many distance metrics for phylogenetic trees focus on trees defined on the same set of taxa. However, some problems require calculating distances between trees with different but overlapping sets of taxa. This study reviews state‐of‐the‐art distance measures for such trees, covering six major approaches, including the constraint‐based Robinson–Foulds (RF) distance RF(−), the completion‐based RF(+), the generalized RF (GRF), the dissimilarity measure, the vectorial tree distance, and the geodesic distance in the extended Billera‐Holmes‐Vogtmann tree space. Among these, three RF‐based methods, RF(−), RF(+), and GRF, were examined in detail on generated clusters of phylogenetic trees defined on different but mutually overlapping sets of taxa. Additionally, we reviewed nine related techniques, including leaf imputation methods, the tree edit distance, and visual comparison. A comparison of the related distance measures, highlighting their principal advantages and shortcomings, is provided. This review offers valuable insights into their applicability and performance, guiding the appropriate use of these metrics based on tree type (rooted or unrooted) and information type (topological or branch lengths).

Abstract Threatening public health, pulmonary disease (PD) encompasses diverse lung injuries like chronic obstructive PD, pulmonary fibrosis, asthma, pulmonary infections due to pathogen invasion, and fatal lung cancer. The crucial involvement of RNA epigenetic modifications in PD pathogenesis is underscored by robust evidence. These modifications not only shape cell fates but also finely modulate the expression of genes linked to disease progression, suggesting their utility as biomarkers and targets for therapeutic strategies. The critical RNA modifications implicated in PDs are summarized in this review, including N6‐methylation of adenosine, N1‐methylation of adenosine, 5‐methylcytosine, pseudouridine (5‐ribosyl uracil), 7‐methylguanosine, and adenosine to inosine editing, along with relevant regulatory mechanisms. By shedding light on the pathology of PDs, these summaries could spur the identification of new biomarkers and therapeutic strategies, ultimately paving the way for early PD diagnosis and treatment innovation.

Abstract Background Pu'er Traditional Tea Agroecosystem is one of the projects included in the United Nations' Globally Important Agricultural Heritage Systems (GIAHS) since 2012. Against the background of having rich biodiversity and a long history of tea culture, the ancient tea trees in Pu'er have experienced from wild–transition–cultivation for thousands of years, and the local people's knowledge about the management of ancient teagardens has not been rigorously recorded. For this reason, it is important to study and record the traditional management knowledge of Pu'er ancient teagardens and the influence on the formation of tea trees and communities. This study focuses on the traditional management knowledge of ancient teagardens in Jingmai Mountains, Pu'er, and monoculture teagardens (monoculture and intensively managed planting base for tea cultivation) were used as the control, through the community structure, composition and biodiversity of ancient teagardens to respond to the influence of traditional management, and this work with a view to providing a reference for further research on the stability and sustainable development of tea agroecosystem. Methods From 2021 to 2022, information on traditional management of ancient teagardens was obtained through semi-structured interviews with 93 local people in the Jingmai Mountains area of Pu'er. Informed consent was obtained from each participant before conducting the interview process. The communities, tea trees and biodiversity of Jingmai Mountains ancient teagardens (JMATGs) and monoculture teagardens (MTGs) were examined through field surveys, measurements and biodiversity survey methods. The Shannon-Weiner (H), Pielou (E) and Margalef (M) indices were calculated for the biodiversity of the teagardens within the unit sample, using monoculture teagardens as a control. Results The tea tree morphology, community structure and composition of Pu'er ancient teagardens are significantly different from those of monoculture teagardens, and the biodiversity is significantly higher than that of monoculture teagardens. The local people mainly manage the ancient tea trees mainly using several methods, including weeding (96.8%), pruning (48.4%) and pest control (33.3%). The pest control mainly relies on the removal of diseased branches. JMATGs annual gross output is approximately 6.5 times that of MTGs. The traditional management of ancient teagardens is through setting up forest isolation zones as protected areas, planting tea trees in the understory on the sunny side, keeping tea trees 1.5–7 m apart, as well as consciously protecting forest animals such as spiders, birds and bees, and reasonably rearing livestock in the teagardens. Conclusions This study shows that local people have rich traditional knowledge and experience in the management of ancient teagardens in Pu'er, and that this traditional management knowledge has impacted the growth of ancient tea trees, enriched the structure and composition of tea plantation communities and actively protected the biodiversity within ancient teagardens.

Bats, with their virus tolerance, social behaviors, and mobility, are reservoirs for emerging viruses, including coronaviruses (CoVs) known for genetic flexibility. Studying the cophylogenetic link between bats and CoVs provides vital insights into transmission dynamics and host adaptation. Prior research has yielded valuable insights into phenomena such as host switching, cospeciation, and other dynamics concerning the interaction between CoVs and bats. Nonetheless, a distinct gap exists in the current literature concerning a comparative cophylogenetic analysis focused on elucidating the contributions of sequence fragments to the co-evolution between hosts and viruses. In this study, we analyzed the cophylogenetic patterns of 69 host–virus connections. Among the 69 host–virus links examined, 47 showed significant cophylogeny based on ParaFit and PACo analyses, affirming strong associations. Focusing on two proteins, ORF1ab and spike, we conducted a comparative analysis of host and CoV phylogenies. For ORF1ab, the specific window ranged in multiple sequence alignment (positions 520–680, 770–870, 2930–3070, and 4910–5080) exhibited the lowest Robinson–Foulds (RF) distance (i.e., 84.62%), emphasizing its higher contribution in the cophylogenetic association. Similarly, within the spike region, distinct window ranges (positions 0–140, 60–180, 100–410, 360–550, and 630–730) displayed the lowest RF distance at 88.46%. Our analysis identified six recombination regions within ORF1ab (positions 360–1390, 550–1610, 680–1680, 700–1710, 2060–3090, and 2130–3250), and four within the spike protein (positions 10–510, 50–560, 170–710, and 230–730). The convergence of minimal RF distance regions with combination regions robustly affirms the pivotal role of recombination in viral adaptation to host selection pressures. Furthermore, horizontal gene transfer reveals prominent instances of partial gene transfer events, occurring not only among variants within the same host species but also crossing host species boundaries. This suggests a more intricate pattern of genetic exchange. By employing a multifaceted approach, our comprehensive strategy offers a nuanced understanding of the intricate interactions that govern the co-evolutionary dynamics between bat hosts and CoVs. This deeper insight enhances our comprehension of viral evolution and adaptation mechanisms, shedding light on the broader dynamics that propel viral diversity.

We define a new algebraic invariant of a graph G called the Ceresa–Zharkov class and show that it is trivial if and only if G is of hyperelliptic type, equivalently, G does not have as a minor the complete graph on four vertices or the loop of three loops. After choosing edge lengths, this class specializes to an algebraic invariant of a tropical curve with underlying graph G that is closely related to the Ceresa cycle for an algebraic curve defined over $\mathbb {C}(\!(t)\!)$ .

Previously, it was believed that type III interferon (IFN-III) has functions similar to those of type I interferon (IFN-I). However, recently, emerging findings have increasingly indicated the non-redundant role of IFN-III in innate antiviral immune responses. Still, the regulatory activity of IFN-III in adaptive immune response has not been clearly reported yet due to the low expression of IFN-III receptors on most immune cells. In the present study, we reviewed the adjuvant, antiviral, antitumor, and disease-moderating activities of IFN-III in adaptive immunity; moreover, we further elucidated the mechanisms of IFN-III in mediating the adaptive antiviral immune response in a thymic stromal lymphopoietin (TSLP)-dependent manner, a pleiotropic cytokine involved in mucosal adaptive immunity. Research has shown that IFN-III can enhance the antiviral immunogenic response in mouse species by activating germinal center B (GC B) cell responses after stimulating TSLP production by microfold (M) cells, while in human species, TSLP exerts OX40L for regulating GC B cell immune responses, which may also depend on IFN-III. In conclusion, our review highlights the unique role of the IFN-III/TSLP axis in mediating host adaptive immunity, which is mechanically different from IFN-I. Therefore, the IFN-III/TSLP axis may provide novel insights for clinical immunotherapy.

Abstract Background Shexian Dryland Stone Terraced System (SDSTS) in the Taihang Mountains was formally recognized as Globally Important Agricultural Heritage Systems (GIAHS) by Food and Agriculture Organization on May 20, 2022. People there have been relying on the terraced fields for centuries, using various plants, including medicinal plants. However, little information was reported about the flora in SDSTS, nor medicinal plants. Thus, the present study aims to identify and document medicinal plants traditionally used by the local people living around the SDSTS and associated ethnobotanical knowledge. Methods We conducted investigations in Shexian County, Hebei Province, North China, where SDSTS is distributed. Then, Wangjinzhuang, a community located in the core zone of SDSTS, was chosen as the case site. We selected the informants through purposive and snowball sampling. The data were collected through semi-structured interviews, participant observation, and key informant interviews. The medicinal plants traditionally used by the local people were documented and analyzed. We examined and confirmed the botanical identification based on voucher specimens and by cross-checking the descriptions with the series of books, scientific papers on medicinal plants, and the plant databases. Results The local people have rich traditional knowledge to collect and use medicinal plants in SDSTS. Records of 123 medicinal plant species belonging to 51 families were obtained from SDSTS. Asteraceae was represented by 16 species, followed by Fabaceae, Lamiaceae and Ranunculaceae. (They all have 8 species.) The majority of the reported plant species were commonly processed into decoctions. And 180 diseases affecting humans were reported to be treated with traditional medicinal plants from SDSTS. Conclusion It is the first ethnobotanical study on medicinal plants in China-Nationally Important Agricultural Heritage Systems, and in globally important agricultural heritage systems as well. Medicinal plants are crucial for people living in Shexian County. It is necessary to recognize and respect traditional knowledge peculiar to the mountainous region of northern China, especially for those involved in the human–nature interaction and the role of knowledge in agrobiodiversity conservation and rural development that local residents have persisted for centuries.

Abstract Background Ovarian cancer (OC) is a major cause of cancer-related deaths among women. The aim of this study was to estimate and report data on the current burden of ovarian cancer worldwide over the past 30 years. Method Based on the data provided by GBD 2019, we collected and interpreted the disease data of ovarian cancer by incidence, mortality, disability-adjusted life-years (DALYs), and used corresponding age-standardized rates as indicators. Also, we categorized the data by attributed risk factors and captured deaths due to high fasting plasma glucose, occupational exposure to asbestos and high body-mass index, respectively. All outcomes in the study were reported using mean values and corresponding 95% uncertainty intervals (95% UI). Results Globally, there were 294422 (260649 to 329727) incident cases in 2019, and the number of deaths and DALYs were 198412 (175357 to 217665) and 5.36 million (4.69 to 5.95). The overall burden was on the rise, with a percentage change of 107.8% (76.1 to 135.7%) for new cases, 103.8% (75.7 to 126.4%) for deaths and 96.1% (65.0 to 120.5%) for DALYs. Whereas the age-standardized rates kept stable during 1990–2019. The burden of ovarian cancer increased with age. and showed a totally different trends among SDI regions. Although high SDI region had the declining rates, the burden of ovarian cancer remained stable in high-middle and low SDI regions, and the middle and low-middle SDI areas showed increasing trends. High fasting plasma glucose was estimated to be the most important attributable risk factor for ovarian cancer deaths globally, with a percentage change of deaths of 7.9% (1.6 to 18.3%), followed by occupational exposure to asbestos and high body mass index. Conclusions Although the age-standardized rates of ovarian cancer didn’t significantly change at the global level, the burden still increased, especially in areas on the lower end of the SDI range. Also, the disease burden due to different attributable risk factors showed heterogeneous, and it became more severe with age.

Let l be a prime and G a pro-l group with torsion-free abelianization. We produce group-theoretic analogues of the Johnson/Morita cocycle for G -- in the case of surface groups, these cocycles appear to refine existing constructions when l=2. We apply this to the pro-l etale fundamental groups of smooth curves to obtain Galois-cohomological analogues, and discuss their relationship to work of Hain and Matsumoto in the case the curve is proper. We analyze many of the fundamental properties of these classes and use them to give an example of a non-hyperelliptic curve whose Ceresa class has torsion image under the l-adic Abel-Jacobi map.

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine that is involved in the pathogenesis of inflammatory diseases and asthma, but the expression and biological implications of the existence of two isoforms, long TSLP (lTSLP) and short TSLP (sTSLP), in RA have yet to be elucidated. Here we report that lTSLP is the predominant TSLP isoform in RA and active RA, whereas sTSLP is the major TSLP isoform in inactive RA and healthy controls. lTSLP expression is associated with disease activity, including 28-joint Disease Activity Score (DAS28) and erythrocyte sedimentation rate (ESR), as well as proinflammatory cytokine expression, irrespective of other laboratory parameters. Importantly, lTSLP alone or combined with LPS promotes the expression of proinflammatory cytokines IL-1β, IL-6, and IL-8 in PBMCs of RA, but restrains anti-inflammatory cytokine IL-10 expression in PBMCs of RA. Furthermore, we found that STAT5 signaling is involved in lTSLP-induced inflammatory accumulation in PBMCs of RA. Therefore, these results highlight the clinical significance of lTSLP in RA pathology and inflammatory response in acute-phase disease, which may provide a therapeutic target for RA.

Host defense peptides (HDPs) are one of the potentially promising agents for infection diseases due to their broad spectrum and low resistance rate, but their clinical applications are limited by proteolytic instability, high-cost, and complicated synthesis process. Here, we report a host-defense-peptide-mimicking β-peptide polymer that resists proteolysis to have enhanced the activity under physiological conditions, excellent antimicrobial efficiency even at high density of bacteria, and low cost for preparation. The β-peptide polymer demonstrated quorum sensing (QS) interference and bactericidal effect against both bacterial communities and individual bacterium to simultaneously block bacterial communication and disrupt bacterial membranes. The hierarchical QS network was suppressed, and main QS signaling systems showed considerably down-regulated gene expression, resulting in excellent biofilm eradication and virulence reduction effects. The dual-modal antibacterial ability possessed excellent therapeutic effects in Pseudomonas aeruginosa pneumonia, which could inhibit biofilm formation and exhibit better antibacterial and anti-inflammatory efficiency than clinically used antibiotics, levofloxacin. Furthermore, the β-peptide polymer also showed excellent therapeutic effect Escherichia coli pyogenic liver abscess. Together, we believed that the β-peptide polymer had a feasible clinical potential to treat bacterial infection diseases.

Most applications of aggregation-induced emission luminogens (AIEgens) have been limited in small animal models. Here, the authors show the versatility of AIEgens-based imaging-guided surgical operation from small animals to rhesus macaque, in support of the clinical translation of AIEgens.

Pyogenic liver abscess and keratitis are aggressive bacterial infections and the treatment has failed to eradicate bacteria in infectious sites completely owing to the currently severe drug resistance to existing antibiotics. Here, we report a simple and efficient one-step development of ultrasmall non-antibiotic nanoparticles (ICG-Ga NPs) containing clinically approved gallium (III) (Ga3+) and liver targeting indocyanine green (ICG) molecules to eradicate multi-drug resistant (MDR) bacteria thought the synergetic effect of photodynamic therapy and iron metabolism blocking. The ICG-Ga NPs induced photodynamic effect could destroy the bacterial membrane, further boost the endocytosis of Ga3+, then replace iron in bacteria cells to disrupt bacterial iron metabolism, and demonstrate the synergetic bacterial killing and biofilm disrupting effects. The ICG-Ga NPs show an excellent therapeutic effect against extended spectrum β-lactamases Escherichia coli (ESBL E. coli) and significantly improve treatment outcomes in infected liver abscess and keratitis. Meanwhile, the ultrasmall size of ICG-Ga NPs could be cleared rapid via renal clearance route, guaranteeing the biocompatibility. The protective effect and good biocompatibility of ICG-Ga NPs will facilitate clinical treatment of bacteria infected diseases and enable the development of next-generation non-antibiotic antibacterial agents.

Abstract Background Males and females differ in their immunological responses to foreign pathogens. However, most of the current COVID-19 clinical practices and trials do not take the sex factor into consideration. Methods We performed a sex-based comparative analysis for the clinical outcomes, peripheral immune cells, and severe acute respiratory syndrome coronavirus (SARS-CoV-2) specific antibody levels of 1558 males and 1499 females COVID-19 patients from a single center. The lymphocyte subgroups were measured by Flow cytometry. The total antibody, Spike protein (S)-, receptor binding domain (RBD)-, and nucleoprotein (N)- specific IgM and IgG levels were measured by chemiluminescence. Results We found that male patients had approximately two-fold rates of ICU admission (4.7% vs. 2.7% in males and females, respectively, P = 0.005) and mortality (3% vs. 1.4%, in males and females, respectively, P = 0.004) than female patients. Survival analysis revealed that the male sex is an independent risk factor for death from COVID-19 (adjusted hazard ratio [HR] = 2.22, 95% confidence interval [CI]: 1.3–3.6, P = 0.003). The level of inflammatory cytokines in peripheral blood was higher in males during hospitalization. The renal (102/1588 [6.5%] vs. 63/1499 [4.2%], in males and females, respectively, P = 0.002) and hepatic abnormality (650/1588 [40.9%] vs. 475/1499 [31.7%], P = 0.003) were more common in male patients than in female patients. By analyzing dynamic changes of lymphocyte subsets after symptom onset, we found that the percentage of CD19+ B cells and CD4+ T cells was generally higher in female patients during the disease course of COVID-19. Notably, the protective RBD-specific IgG against SARS-CoV-2 sharply increased and reached a peak in the fourth week after symptom onset in female patients, while gradually increased and reached a peak in the seventh week after symptom onset in male patients. Conclusions Males had an unfavorable prognosis, higher inflammation, a lower percentage of lymphocytes, and indolent antibody responses during SARS-CoV-2 infection and recovery. Early medical intervention and close monitoring are important, especially for male COVID-19 patients.

Background Deep learning has been widely used for glaucoma diagnosis. However, there is no clinically validated algorithm for glaucoma incidence and progression prediction. This study aims to develop a clinically feasible deep-learning system for predicting and stratifying the risk of glaucoma onset and progression based on color fundus photographs (CFPs), with clinical validation of performance in external population cohorts.Methods We established data sets of CFPs and visual fields collected from longitudinal cohorts. The mean follow-up duration was 3 to 5 years across the data sets. Artificial intelligence (AI) models were developed to predict future glaucoma incidence and progression based on the CFPs of 17,497 eyes in 9346 patients. The area under the receiver operating characteristic (AUROC) curve, sensitivity, and specificity of the AI models were calculated with reference to the labels provided by experienced ophthalmologists. Incidence and progression of glaucoma were determined based on longitudinal CFP images or visual fields, respectively.Results The AI model to predict glaucoma incidence achieved an AUROC of 0.90 (0.81–0.99) in the validation set and demonstrated good generalizability, with AUROCs of 0.89 (0.83–0.95) and 0.88 (0.79–0.97) in external test sets 1 and 2, respectively. The AI model to predict glaucoma progression achieved an AUROC of 0.91 (0.88–0.94) in the validation set, and also demonstrated outstanding predictive performance with AUROCs of 0.87 (0.81–0.92) and 0.88 (0.83–0.94) in external test sets 1 and 2, respectively.Conclusion Our study demonstrates the feasibility of deep-learning algorithms in the early detection and prediction of glaucoma progression.FUNDING National Natural Science Foundation of China (NSFC); the High-level Hospital Construction Project, Zhongshan Ophthalmic Center, Sun Yat-sen University; the Science and Technology Program of Guangzhou, China (2021), the Science and Technology Development Fund (FDCT) of Macau, and FDCT-NSFC.

Understanding antibody responses to Sars-CoV-2 proteins over time is complicated by many variables. Here the authors survey IgM and IgG antibodies against S protein, RBD and nucleoprotein in a large cohort of infected and recovering severe vs. moderate COVID-19 patients, comparing against clinical parameters and immunological readouts.

Chrysin has been proven to possess antiviral properties, but the precise underlying anti-influenza mechanism and its anti-influenza efficacy in vivo are largely unclear. In this study, we investigated the involvement of chrysin in the blockade of cell cycle and apoptosis in distinct cell lines subjected to two H1N1 influenza A virus (IAV) strains, as well as its anti-IAV activity in vivo. Here, we found an early unidentified finding that chrysin strongly impeded IAV replication through a mechanism that was autonomous of innate antiviral immune activation and viral protein interaction. Surprisingly, chrysin can suppress IAV-induced cell cycle arrest in the G0/G1 phase by downregulating the expression levels of P53 and P21 while promoting Cyclin D1/CDK4 and Cyclin E1/CDK2 activation. Furthermore, chrysin dramatically inhibited the IAV-triggered mitochondrial apoptotic pathway by altering the balance of Bax/Bcl-xl and reducing caspase-9 and caspase-3 activation. Accumulated reactive oxygen species (ROS) reduction may contribute to the inhibitory role of chrysin in cell cycle arrest and apoptosis following IAV infection. Notably, chrysin preferably inhibited IAV replication in the upper respiratory tract, indicating that it might be a promising drug for restraining the spread of respiratory viruses.

We examined the effects of nitrate nitrogen fertilizer (N), biochar (BC) and arbuscular mycorrhizal fungi (AMF) on Trifolium pratense mycorrhizal colonization, dry mass, nutrient and pollutant accumulation and soil AMF community, aiming to determine a potential approach that is beneficial to clover growth and AMF community under contaminated environment. Result showed that soil pH increased from 6.88 to 7.01 in the presence of N in combination BC treatments. Compared to control, N in combination BC treatments significantly decreased DTPA-Zn, Pb, Cd, As and Cu concentrations, and the average reduction for DTPA-Zn, Pb, Cd, As and Cu concentration by 53.2, 52.5, 48.8, 44.5 and 45.5%, respectively. Root colonization, shoot and root dry masses were increased when receiving both N and BC. On average, the shoot P, Zn, Pb, Cd and As levels were reduced by 39.7, 62.4, 86.7, 84.6 and 87.8% when receiving both N and BC and simultaneously the root Cd and Zn concentrations were reduced by 64.9 and 55.8%, respectively. DTPA-extractable Cd, Zn and Pb were positively correlated to shoot Zn, Pb and Cd concentrations as well as root Zn and Cd concentrations but negatively correlated with pH. Moreover, Glomus species were the soil major AMF present with all treatments. The combination N and BC treatments increased Glomus abundance but did not affect overall AMF diversity. Soil pH, DTPA-Cd, Zn, Pb and Cu had greater effect on AMF community structure as assessed by redundancy analysis (RDA). Glomus abundance was positively related to pH, root colonization, shoot and root dry mass and negatively related to DTPA-Cd, Zn, Pb and Cu. A network analysis indicated that BC and N addition promoted synergistic interactions among Glomus species. Our results demonstrated that the N in combination BC treatments can promote plant growth while decreasing pollutant accumulation in shoot and root, and the N and BC addition can increase Glomus abundance and their synergistic interactions under multi-contaminated soil.

China’s Belt and Road (B&R) initiative provides new ideas and opportunities for international cooperation. Renewable energy plays a crucial role not only in the national sustainable development framework of China and the Philippines but also in bilateral cooperation between them. However, some obstacles still need to be addressed because renewable energy cooperation between China and the Philippines has not been thoroughly and comprehensively studied to date. Based on an in-depth analysis of current renewable energy cooperation between China and the Philippines, this paper employs PESTEL analysis to fully investigate the cooperative advantages and disadvantages by considering politics (P), economy (E), society (S), technology (T), environment (E), and legislation (L) and proposes several constructive suggestions. The ultimate purpose was to design feasible schemes to ensure the sufficient utilization of renewable energy and the construction of integrated power grid systems to meet shortages of electricity supply especially in the isolated small islands in the Philippines through cooperation with China. In particular, it offers valuable advice concerning the U.S.-China trade war and COVID- 19 pandemic, outlining how cooperation in the exploitation of potential renewable energy is vital.

As the biggest country in power consumption and generation, China owns the largest scale of transmission line worldwide. The application of unmanned aerial vehicle (UAV) in inspection has been carried out for many years in China because of its strong adaptability and safety compared to the traditional manual way. For the further development of UAV application technology in transmission line inspection, China has accumulated rich experiences and greatly improved line inspection efficiency and formed a relatively complete UAV transmission line inspection standardization system including operation safety management, an equipment configuration method, and functional quality requirements. However, there still exist some obstacles that need to be tackled due to the fact that China’s UAV transmission line inspection standardization and its international promotion have not been thoroughly and comprehensively studied at present. Based on an in-depth analysis of China’s current UAV transmission line inspection standardization system, this study employs SWOT-PEST analysis to insightfully investigate international promotion opportunities/challenges under the current situation, upon which several constructive suggestions are proposed from four aspects of politics, economy, society, and technology. The ultimate purpose is to design feasible schemes to boost the international promotion of China’s UAV transmission line inspection standardization and further development of international UAV inspection technology.

In this paper, the prediction of over-the-top service quality is discussed, which is a promising way for mobile network engineers to tackle service deterioration as early as possible. Currently, traditional mobile network operation often takes appropriate remedial measures, when receiving customers’ complaints about service problems. With the popularity of over-the-top services, this problem has become increasingly serious. Based on the service perception data crowd-sensed from massive smartphones in the mobile network, we first investigated the application of multi-label ReliefF, a well-known method of feature selection, in determining the feature weights of the perception data and propose a unified multi-label ReliefF (UML-ReliefF) algorithm. Then a feature-weighted multi-label k-nearest neighbor (ML-kNN) algorithm is proposed for the key quality indicators (KQI) prediction, by combining the UML-ReliefF and ML-kNN together in the learning. The experimental results for web browsing service show that UML-ReliefF can effectively identify the most influential features of the data and thus, lead to better performance for KQI prediction. The experiments also show that the feature-weighted KQI prediction is superior to its unweighted counterpart, since the former takes full advantage of all the features in the learning. Although there is still much room of improvement in the precision of the prediction, the proposed method is highly potential for network engineers to find the deterioration of service quality promptly and take measures before it is too late.

Oomycete pathogens produce a large number of CRN effectors to manipulate plant immune responses and promote infection. However, their functional mechanisms are largely unknown. Here, we identified a Phytophthora sojae CRN effector PsCRN108 which contains a putative DNA-binding helix-hairpin-helix (HhH) motif and acts in the plant cell nucleus. Silencing of the PsCRN108 gene reduced P. sojae virulence to soybean, while expression of the gene in Nicotiana benthamiana and Arabidopsis thaliana enhanced plant susceptibility to P. capsici. Moreover, PsCRN108 could inhibit expression of HSP genes in A. thaliana, N. benthamiana and soybean. Both the HhH motif and nuclear localization signal of this effector were required for its contribution to virulence and its suppression of HSP gene expression. Furthermore, we found that PsCRN108 targeted HSP promoters in an HSE- and HhH motif-dependent manner. PsCRN108 could inhibit the association of the HSE with the plant heat shock transcription factor AtHsfA1a, which initializes HSP gene expression in response to stress. Therefore, our data support a role for PsCRN108 as a nucleomodulin in down-regulating the expression of plant defense-related genes by directly targeting specific plant promoters.

Abstract How do illegal markets operate in cyberspace? Drawing on interview data, this article examines the organizational structure of China’s illegal online gambling businesses and their use of extralegal governance institutions to marketize services, ensure fair play, enforce compliance, and reduce the risk of prosecution. The article also discusses the impact of China’s intensified efforts to repress illegal markets. It suggests that operators in the illegal online market now prefer to settle gambling debts using ex ante means, such as deposits, rather than ex post mechanisms, such as using interpersonal obligations or violence to enforce debt collection. This research contributes to the literature on extralegal governance, gambling, and illegal markets.

Abstract Purpose This review primarily discusses the current research advance of predictive biomarkers for melanoma immunotherapy. The aim of the present review is to summarize the biomarkers and evaluate the advantages and disadvantages. Methods All reference can be found through Pubmed. This review mainly focuses on three main directions: tumor-related factors, host factors, and the tumor microenvironment. In the end, there exhibits some unusual aspects of predictive biomarkers and forecasts the future model. Results The mainsteam of predictive biomarkers focuses on PD-L1, TMB, gene mutations, immune cells, IDO1, LDH, tertiary lymphoid structures (TLS), HLA-DR, tumor-associated macrophages (TAMs), tumor-infiltrating lymphocytes (TILs), and Extracellular vesicles (EVs). Conclusion The current research advance of predictive biomarkers for melanoma immunotherapy can be mainly divided into three parts: tumor-related factors, host factors, and the tumor microenvironment. The predictive biomarkers include PD-L1, TMB, gene mutations, immune cells, IDO1, LDH, TLS, HLA-DR, TAMs, TILs, and EVs. A model based on multiple biomarkers is expected to become the answer to predicting prognosis.

Let ℓ be a prime and G a pro-ℓ group with torsion-free abelianization. We produce group-theoretic analogues of the Johnson/Morita cocycle for G-in the case of surface groups, these cocycles appear to refine existing constructions when ℓ = 2. We apply this construction to the pro-ℓ étale fundamental groups of smooth curves to obtain Galois-cohomological analogues of these cocycles, which represent what we call the "modified diagonal" and "Johnson" classes, and discuss their relationship to work of Hain and Matsumoto in the case where the curve is proper. We analyze many of the fundamental properties of these classes and use them to give two examples of non-hyperelliptic curves whose Ceresa class has torsion image under the ℓ-adic Abel-Jacobi map. [ABSTRACT FROM AUTHOR]

IntroductionPituitary carcinoma (PC) is an extremely rare tumor of the adenohypophysis, which manifests as craniospinal dissemination and/or systemic metastasis. The diagnosis of PC is particularly difficult, as the clinical diagnosis only can be made after the metastasis is found. Owing to the complex diagnostic process and less effective treatments, the clinical prognosis of PC is usually very poor. Hence, it is of great significance to illustrate the diagnosis and treatment course of PC.MethodsIn this case report, we described a 48-year-old male patient who was diagnosed with pituitary adenoma (PA) initially and then was diagnosed with PC eventually after spinal cord metastasis was found, and we illustrated the treatment course as well. Furthermore, we summarized all the published case reports until now and provided a comprehensive review of the diagnosis, treatment, prediction, and clinical outcome of PC.Results and ConclusionsWe found that most PC patients had adrenocorticotropic hormone/prolactin (ACTH/PRL)-secreting tumors, Ki-67 ≥ 10%, and P53 positivity, which may have the potential to predict the transformation from PA to PC; surgery excision combined with temozolomide (TMZ) and radiotherapy is helpful to prolong the survival of PC patients.

Abstract High-performance active terahertz modulators as the indispensable core components are of great importance for the next generation communication technology. However, they currently suffer from the tradeoff between modulation depth and speed. Here, we introduce two-dimensional (2D) tellurium (Te) nanofilms with the unique structure as a new class of optically controlled terahertz modulators and demonstrate their integrated heterojunctions can successfully improve the device performances to the optimal and applicable levels among the existing all-2D broadband modulators. Further photoresponse measurements confirm the significant impact of the stacking order. We first clarify the direction of the substrate-induced electric field through first-principles calculations and uncover the unusual interaction mechanism in the photoexcited carrier dynamics associated with the charge transfer and interlayer exciton recombination. This advances the fundamental and applicative research of Te nanomaterials in high-performance terahertz optoelectronics.

Objective: Osteosarcoma (OS) is the most common primary bone sarcoma with a high propensity for local invasion and metastasis. Although the antitumor effect of apatinib has been well confirmed in advanced OS, the synergistic effect of apatinib and immunotherapies has not yet been elucidated. Methods: In this study, we established tumour-bearing mice and observed tumour size with low and high doses of apatinib treatments. The expression of 17 cytokines, including vascular endothelial growth factor (VEGF), was detected by protein microarray analysis. Moreover, we designed apatinib and antigen-specific dendritic cell (DC)-T combination treatment for tumour-bearing mice. Tumour growth was detected by statistical analysis of tumour size and microvessel density (MVD) counting, the protein expression of VEGF by western blotting, the cytokines interleukin 6 (IL-6), IL-17 and interferon-gamma (IFN-γ) by enzyme-linked immunosorbent assay (ELISA), and the numbers of myeloid-derived suppressor cells (MDSCs) and tumour-infiltration macrophages (TAMs) by flow cytometry. Results: The results showed that apatinib efficiently suppressed tumour growth, and high-dose apatinib achieved a stronger effect. The same was true for DC-T immunotherapy. However, their combination treatment revealed a better oncolytic effect. Meanwhile, apatinib or DC-T treatment inhibited the expression of VEGF and the proangiogenic mediators IL-6 and IL-17 but increased IFN-γ production. Combination therapy further reduced/increased these effects. In addition, the combination treatment reduced MDSC but enhanced TAM-M1 ratios in the OS microenvironment. These findings indicated that apatinib and antigen-specific DC-T combination therapy was more efficient in oncolysis by regulating pro-/anti-angiogenic inducers and improving the immune state in the OS microenvironment. Conclusion: This study proved that it was feasible to employ immunotherapy with therapeutic agents in OS treatment, which may provide a new approach in addition to the combination of surgery with chemotherapy in tumour treatment.

Abstract Acral melanoma (AM) is a rare subtype of melanoma characterized by a high incidence of lymph node (LN) metastasis, a critical factor in tumor dissemination and therapeutic decision-making. Here, we employ single-cell and spatial transcriptomic analyses to investigate the dynamic evolution of early AM dissemination. Our findings reveal substantial inter- and intra-tumor heterogeneity in AM, alongside a highly immunosuppressive tumor microenvironment and complex intercellular communication networks, particularly in patients with LN metastasis. Notably, we identify a strong association between MYC + Melanoma (MYC +MEL) and FGFBP2 +NKT cells with LN metastasis. Furthermore, we demonstrate that LN metastasis requires a metabolic shift towards fatty acid oxidation (FAO) induced by MITF in MYC +MEL cells. Etomoxir, a clinically approved FAO inhibitor, can effectively suppress MITF-mediated LN metastasis. This comprehensive dataset enhances our understanding of LN metastasis in AM, and provides insights into the potential therapeutic targeting for the management of early AM dissemination.

Abstract Background The ongoing coronavirus disease 2019 (COVID-19) pandemic has had an enormous impact on our societies. Moreover, the disease’s extensive and sustained symptoms are now becoming a nonnegligible medical challenge. In this respect, data indicate that heart failure is one of the most common readmission diagnoses among COVID-19 patients. Methods In this study, we used human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes to develop an in vitro model of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and studied the dynamic changes occurring in cardiomyocytes after SARS-CoV-2 infection. Results To this end, we have created an effective time series SARS-CoV-2 infection model exhibiting different functional patterns of up- and downregulated proteins, and demonstrating that SARS-CoV-2 mainly affects (i) the lipid and the energy metabolism of hiPSC-derived cardiomyocytes during the early infection stage, and (ii) the DNA repair ability of cardiomyocytes during the late infection stage. By analyzing the proteome changes occurring at different infection timepoints, we were able to observe that the simulated disease (COVID-19) course developed rapidly, and that each of the studied timepoints was characterized by a distinct protein expression pattern. Conclusions Our findings highlight the importance of early detection and personalized treatment based on the disease stage. Finally, by combing the proteomics data with virus-host interaction network analysis, we were able to identify several potential drug targets for the disease.