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Abstract Deciphering the driving forces behind spatial heterogeneity of regional hydroclimate changes is significant for developing strategies for water management. This study presents speleothem δ18O, δ13C and Mg/Ca records spanning the last deglaciation from Yingpan Cave, northeastern Yunnan in southwestern China. Speleothem δ13C and Mg/Ca indicate a gradual drying trend in northeastern Yunnan, aligning well with the variations in central China but contrasting with those of central-southern Yunnan. We propose that a decreased zonal sea surface temperature (SST) gradient in tropical Pacific (El Niño-like) shifted the West Pacific Subtropical High (WPSH) southwestward, leading to wetter conditions in northeastern Yunnan. Meanwhile, decreased precipitation in central-southern Yunnan was driven by weakened Indian summer monsoon rainfall associated with El Niño-like conditions, creating a dipolar hydrological pattern in Southwest China. Our results indicate that the spatial heterogeneity of hydroclimate can be modulated by the same triggers but have different processes and mechanisms and hence responses.

Abstract Given growing concerns about global climate change, it is critical to understand both historical and current shifts in the hydroclimate, particularly in regions critically entwined with global circulation. The Tibetan Plateau, the Earth’s largest and highest plateau, is a nexus for global atmospheric processes, significantly influencing East Asian hydroclimate dynamics through the synergy of the Asian Monsoon and the Westerlies. Yet, understanding historical and recent hydroclimate fluctuations and their wide-ranging ecological and societal consequences remains challenging due to short instrumental observations and partly ambiguous proxy reconstructions. Here, we present a precisely-dated 3476-year precipitation reconstruction derived from tree-ring δ18O data on the Tibetan Plateau, representing one of the few multi-millennia-long annually-resolved terrestrial δ18O records to date. Our findings reveal that the 20th century drought extremes are severe within the past three millennia, and likely linked to the weakening of both the Asian Monsoon and Westerlies due to anthropogenic aerosol emissions. Additionally, our analyses identified three distinct stages (110 BC–AD 280, AD 330–770 and AD 950–1300) characterized by shifts toward arid hydroclimate conditions, corresponding to significant social unrest and dynasty collapses, which underscores the potential societal impacts of severe hydroclimatic shifts.

Sudden water inrush is the primary geological hazard in karst tunnels, which poses significant risks and seriously threatens tunnel construction and safety. To address this issue, this study takes multiple karst tunnels under construction in Guangxi as research objects. Through geological investigation and analysis of the geological conditions and tunnel characteristics in the tunnel areas, this study selects seven key factors affecting tunnel water inrush, including basic quality index of rock mass, rock mass dip angle, rock mass integrity coefficient, surrounding rock saturated uniaxial compressive strength, maximum water inrush of the tunnel, annual rainfall in the tunnel site area during the rainy season, and tunnel burial depth, as evaluation indicators. A combined weighting-TOPSIS method for karst tunnel water inrush risk assessment system is constructed. Hierarchical analysis method is used to establish a judgment matrix to determine the subjective weights of evaluation indicators. Subsequently, the objective weighting entropy method is used to calculate the objective weights, and the combination of the two is used to form a combined weighting method to calculate the combined weights. Finally, based on the combined weighting-TOPSIS method, the distance and relative closeness between the cross-sections of karst tunnels under construction and the ideal solution are obtained to evaluate the risk of water inrush in karst tunnels under construction. The evaluation results have been well validated in advance geological drilling, demonstrating the feasibility of this method for literature evaluation of karst tunnel water inrush.

Abstract Tropical hydroclimate in monsoonal regions has been largely understood according to the orbital monsoon hypothesis, in which rainfall exhibits strong covariation with local summer insolation on precessional (~21,000 years) time scales, as exemplified in the Asian and South American monsoon stalagmite records. However, paleo-rainfall variations in some tropical regions are poorly explained by the orbital hypothesis, suggesting alternative forcing mechanisms of regional monsoon changes. Here, we show a 140,000-year record of Central American rainfall from oxygen-isotope (δ18O) time series of precisely dated stalagmites which reveals two dominant thermally-controlled monsoon regimes in which the Atlantic Ocean thermal state linked to the meridional overturning circulation (AMOC) is the primary driver, and local orbital summer insolation control is limited. Our reconstruction, supported by isotope-enabled climate model simulations, pinpoints the potential impacts of future AMOC weakening on the Central American and Caribbean climate.

Gene transcription is an essential process involved in all aspects of cellular functions with significant impact on biological traits and diseases. This process is tightly regulated by multiple elements that co-operate to jointly modulate the transcription levels of target genes. To decipher the complicated regulatory network, we present a novel multi-view attention-based deep neural network that models the relationship between genetic, epigenetic, and transcriptional patterns and identifies co-operative regulatory elements (COREs). We applied this new method, named DeepCORE, to predict transcriptomes in various tissues and cell lines, which outperformed the state-of-the-art algorithms. Furthermore, DeepCORE contains an interpreter that extracts the attention values embedded in the deep neural network, maps the attended regions to putative regulatory elements, and infers COREs based on correlated attentions. The identified COREs are significantly enriched with known promoters and enhancers. Novel regulatory elements discovered by DeepCORE showed epigenetic signatures consistent with the status of histone modification marks.

Abstract A high‐salt diet can induce hypertension, so salt reduction can prevent hypertension. γ‐Glutamyl peptides (GGPs) have obvious taste‐enhancing effects, while their contents in natural foods are relatively low. Yeast protein rich in Glu/Gln is a good precursor for the preparation of GGPs. In this study, yeast protein‐derived GGPs were prepared through hydrolysis and transpeptidation reactions, followed by sensory evaluation and E‐tongue analysis. Peptide sequences were identified by LC−MS/MS and screened for molecular docking. The optimal reaction conditions were hydrolysis for 4 h, enzyme concentration of 16 U/g, and transpeptidation for 4 h. GGPs could increase salt and umami intensity by 60.78% and 40.93% based on sensory evaluation, 22.52%, and 16.40% according to E‐tongue analysis. Fifteen γ‐glutamyl peptides with different peptide lengths were selected for molecular docking. Molecular docking confirmed their binding to calcium‐sensing receptors (CaSr) through hydrogen bonds and hydrophobic interaction, while interaction between CaSR receptor and γ‐glutamyl di‐, tri‐, and oligo‐peptides varied in binding energy. The stimulation received by CaSR lasted a longer time and varied in intensity. It was further proved that the flavor of mixed peptides has a layered sense and can give people a rich taste experience. Overall, yeast protein‐derived GGPs can enhance salt and umami taste, which can reduce salt usage without compromising taste.

Maize is one of the main food crops and is widely planted in China; however, it is difficult to get timely and precise information on yields. Because of the benefits of remote sensing technology, satellite-based models (e.g., eddy covariance light use efficiency, EC-LUE) have a lot of potential for monitoring crop productivity. In this study, the gross primary productivity (GPP) of maize in the NCP was estimated using the EC-LUE model, and the GPP was subsequently transformed into yield using the harvest index. Specifically accounting for the spatiotemporal variation in the harvest index, the statistical yield and estimated GPP from the previous year were used to generate region-specific harvest indexes at the county scale. The model's performance was assessed using statistical yield data. The results demonstrate that the increase in the total GPP in the summer maize-growing season in the NCP is directly related to the increase in the planting area, and the harvest index has significant heterogeneity in space, and the fluctuation in time is small, and the estimated yield can simulate 64% and 55%, respectively, of the variability in the yield at the county and city scales. The model also accurately captures the inter-annual changes in yield (the average absolute percentage errors are less than 20% for almost all years), but model performance varies by region. It performs better in continuous areas of maize-growing. The results from this study demonstrate that the EC-LUE model can be applied to estimate the yield from a variety of crops (other than winter wheat) and that it can be used in conjunction with a region-specific harvest index to track the production of large-scale crops. [ABSTRACT FROM AUTHOR]

Abstract Speleothem trace element records can provide seasonal resolution climate reconstructions, but the interpretation can be challenging. Aragonite samples are understudied compared to calcite samples, despite that aragonite has 10x higher uranium concentrations and thus provide excellent dating precision. Here we present a high-resolution dataset of drip water trace elements (calcium, magnesium, strontium, barium, uranium) that are commonly affected by prior carbonate (calcite / aragonite) precipitation, a process often driven by effective rainfall. Our data suggest that prior calcite and aragonite precipitation can occur at the same drip site complicating the interpretation of strontium and uranium concentrations in aragonite speleothems. However, both processes can be distinguished with the “Sinclair test” through the trendline analysis of logarithmic relationships. Furthermore, our data show that aragonite speleothems slowly growing under relatively constant conditions are ideal to record variations in prior carbonate precipitation with its barium concentrations, independent from the prior carbonate precipitation mode.

Abstract Identifying tropical cyclone (TC) signatures in paleoclimate records enhances our understanding of long-term TC activity trends and the climatic factors influencing TC evolution. Stalagmites are considered promising archives for recording TC activity. However, despite the western North Pacific being the most TC-active ocean basin globally, it lacks stalagmite-based TC reconstructions. Here, we present a seasonally resolved stalagmite δ18O record from XRY cave in Southeast China, covering the period from 1951 to 2018 CE, to identify annual signals of strong TC activity. We propose that the minimum seasonal XRY δ18O value of each year can reconstruct regional TC activity, achieving an identification rate of 86% for strong TC years in study area. This demonstrates the feasibility of using stalagmites for TC reconstruction in Southeast China. Moreover, our research shows that inland stalagmites can still capture TC activity signals, which will promote the use of stalagmites in obtaining long-term records of post-landfall TC activity and inland impacts.

Background: Peripheral T-cell lymphomas (PTCL) are an aggressive group of mature T-cell neoplasms, often associated with poor outcomes, in part, due to frequent relapsed/refractory disease. The objective of this study was to assess the prognostic impact of disease progression within 24 months (POD24) on overall survival (OS) for patients diagnosed with PTCL.Methods: A retrospective analysis was conducted on a cohort of patients with newly diagnosed PTCL who underwent chemotherapy at the Affiliated Hospital of Xuzhou Medical University between January 2010 and September 2021. Prognostic assessment was limited to patients who were evaluable for POD24.Results: Records were reviewed for 106 patients with PTCL, of whom 66 patients experienced POD24 (referred to as the POD24 group) and 40 patients did not experience POD24 (referred to as the no POD24 group). Significant differences were observed between the POD24 group and the no POD24 group in regard to clinical stage, Eastern Cooperative Oncology Group (ECOG) performance status (PS), International Prognostic Index (IPI) score, lactate dehydrogenase (LDH) levels, β2-microglobulin (β2-MG) levels, prealbumin and albumin levels. Patients in the POD24 group had a significant shorter median OS compared to the no POD24 group (11.9 months vs not reached, respectively; P

Background Several previous cross‐sectional studies suggested that body roundness index (BRI) may be associated with cardiovascular disease (CVD). However, the association should be further validated. Our study aimed to assess the association of the BRI trajectories with CVD among middle‐aged and older Chinese people in a longitudinal cohort. Methods and Results A total of 9935 participants from the CHARLS (China Health and Retirement Longitudinal Study) with repeated BRI measurements from 2011 to 2016 were included. The BRI trajectories were identified by group‐based trajectory modeling. The primary outcome was incident CVD (stroke or cardiac events), which occurred in 2017 to 2020. Cox proportional hazards regression models were used to examine the association of BRI trajectories with CVD risk. Participants were divided into 3 BRI trajectories, named the low‐stable BRI trajectory, moderate‐stable BRI trajectory and high‐stable BRI trajectory, accounting for 49.81%, 42.35%, and 7.84% of the study population, respectively. Compared with participants in the low‐stable BRI trajectory group, those in the moderate‐stable and high‐stable BRI trajectory groups had an increased risk of CVD, with multivariable adjusted hazard ratios of 1.22 (95% CI, 1.09–1.37) and 1.55 (95% CI, 1.26–1.90), respectively. Furthermore, simultaneously adding the BRI trajectory to the conventional risk model improved CVD risk reclassification (all P

Abstract Mitophagy is critical for mitochondrial quality control and function to clear damaged mitochondria. Here, we found that Burkholderia pseudomallei maneuvered host mitophagy for its intracellular survival through the type III secretion system needle tip protein BipD. We identified BipD, interacting with BTB-containing proteins KLHL9 and KLHL13 by binding to the Back and Kelch domains, recruited NEDD8 family RING E3 ligase CUL3 in response to B. pseudomallei infection. Although evidently not involved in regulation of infectious diseases, KLHL9/KLHL13/CUL3 E3 ligase complex was essential for BipD-dependent ubiquitination of mitochondria in mouse macrophages. Mechanistically, we discovered the inner mitochondrial membrane IMMT via host ubiquitome profiling as a substrate of KLHL9/KLHL13/CUL3 complex. Notably, K63-linked ubiquitination of IMMT K211 was required for initiating host mitophagy, thereby reducing mitochondrial ROS production. Here, we show a unique mechanism used by bacterial pathogens that hijacks host mitophagy for their survival.

Abstract The isotopic composition has long been used to investigate the factors influencing precipitation, whereas the variations of event-based precipitation isotopes caused by moisture transition and synoptic meteorological conditions remain limited. Here we present triple oxygen and hydrogen isotopes in event-based precipitation during West China Autumn Precipitation to evaluate the influence of various moisture sources in the hydrological process. Isotopes δ18O, δ17O, and δD peak with convective precipitation at the onset stage, then drop to their lowest amid stratiform precipitation during the middle stage, and rise again towards the end. In contrast, Δ′17O levels remain elevated throughout the mid-stage of West China Autumn Precipitation compared to the onset and end stages. These isotopic variations, coupled with moisture analysis, reveal a distinct moisture source transition from the West Pacific Ocean to the westerly domain during West China Autumn Precipitation accompanied by the retreat of the Asian summer monsoon from Northwest China.

Abstract Despite the high therapeutic response achieved with B-cell maturation antigen (BCMA)-specific chimeric antigen receptor (CAR) T-cell therapy in relapsed and refractory multiple myeloma (R/R MM), primary resistance and relapse exist with single-target immunotherapy. Here, we design bispecific BC19 CAR T cells targeting BCMA/CD19 and evaluate antimyeloma activity in vitro and in vivo. Preclinical results indicate that BC19 CAR specifically recognize target antigens, and BC19 CAR T cells mediate selective killing of BCMA or CD19-positive cancer cells. BC19 CAR T cells also exhibit potent antigen-specific anti-tumor activity in xenograft mouse models. We conduct an open-label, single-arm, phase I/II study of BC19 CAR T cells in 50 patients with R/R MM (ChiCTR2000033567). The primary endpoint was safety. BC19 CAR T cells are well tolerated with grade 3 or higher cytokine release syndrome in 8% of patients and grade 1 neurotoxic events in 4% of patients, which meet the pre-specified primary endpoint. Secondary endpoints include overall response rate (92%), median progression-free survival (19.7 months), median overall survival (19.7 months) and median duration of response (not reached). Our study demonstrates that bispecific BC19 CAR T cells are feasible, safe and effective in treating patients with R/R MM.

Abstract Background The pathogenesis of memory impairment, a common complication of chronic neuropathic pain (CNP), has not been fully elucidated. Schwann cell (SC)-derived extracellular vesicles (EVs) contribute to remote organ injury. Here, we showed that SC-EVs may mediate pathological communication between SCs and hippocampal neurons in the context of CNP. Methods We used an adeno-associated virus harboring the SC-specific promoter Mpz and expressing the CD63-GFP gene to track SC-EVs transport. microRNA (miRNA) expression profiles of EVs and gain-of-function and loss-of-function regulatory experiments revealed that miR-142-5p was the main cargo of SC-EVs. Next, luciferase reporter gene and phenotyping experiments confirmed the direct targets of miR-142-5p. Results The contents and granule sizes of plasma EVs were significantly greater in rats with chronic sciatic nerve constriction injury (CCI)than in sham rats. Administration of the EV biogenesis inhibitor GW4869 ameliorated memory impairment in CCI rats and reversed CCI-associated dendritic spine damage. Notably, during CCI stress, SC-EVs could be transferred into the brain through the circulation and accumulate in the hippocampal CA1-CA3 regions. miR-142-5p was the main cargo wrapped in SC-EVs and mediated the development of CCI-associated memory impairment. Furthermore, α-actinin-4 (ACTN4), ELAV-like protein 4 (ELAVL4) and ubiquitin-specific peptidase 9 X-linked (USP9X) were demonstrated to be important downstream target genes for miR-142-5p-mediated regulation of dendritic spine damage in hippocampal neurons from CCI rats. Conclusion Together, these findings suggest that SCs-EVs and/or their cargo miR-142-5p may be potential therapeutic targets for memory impairment associated with CNP.

Background: Hypovolemia is common in colonoscopy due to fasting and bowel preparation, and propofol itself can reduce systemic vascular resistance, resulting in relative hypovolemia. Therefore, hypotension is not a rare event during propofol-based sedation for colonoscopy. Objectives: Our objective was to explore the efficacy of esketamine as a sedative adjuvant in reducing the incidence of hypotension during colonoscopy. Design: This was a prospective randomized trial. The trial was registered with the Chinese Clinical Trial Registry (ID: ChiCTR 2100047032). Methods: We included 100 eligible patients who planned to receive a colonoscopy and randomly divided them into 4 groups with 25 patients in each group, which were propofol 2 mg/kg (Group P), propofol 1 mg/kg with esketamine 0.2 mg/kg (Group E1), propofol 1 mg/kg with esketamine 0.3 mg/kg (Group E2), and propofol 1 mg/kg with esketamine 0.4 mg/kg (Group E3). The hemodynamic and respiratory parameters were documented at various times during the procedure, including the patient’s entry into the endoscopic room (T0), the induction of sedation (T1), the insertion of the colonoscope (T2), the removal of the colonoscope (T3), and the awakening of the patient (T4). The primary outcome was the incidence of hypotension. Secondary outcomes were cardiovascular side effects other than hypotension, incidence of hypoxia, cumulative changes in cardiovascular and respiratory parameters, total propofol dosage, anesthesia recovery time, and satisfactory levels of both patients and endoscopists. Results: The incidence of hypotension in Group E1 (16%), Group E2 (16%), and Group E3 (12%) was significantly lower than in Group P (60%), with p values 0.003, 0.003, and

Several studies have suggested an association between exposure to various metals and the onset of type 2 diabetes (T2D). However, the results vary across different studies. We aimed to investigate the associations between serum metal concentrations and the risk of developing T2D among 8734 participants using a prospective cohort study design. We utilized inductively coupled plasmamass spectrometry (ICP-MS) to assess the serum concentrations of 27 metals. Cox regression was applied to calculate the hazard ratios (HRs) for the associations between serum metal concentrations on the risk of developing T2D. Additionally, 196 incident T2D cases and 208 healthy control participants were randomly selected for serum metabolite measurement using an untargeted metabolomics approach to evaluate the mediating role of serum metabolite in the relationship between serum metal concentrations and the risk of developing T2D with a nested casecontrol study design. In the cohort study, after Bonferroni correction, the serum concentrations of zinc (Zn), mercury (Hg), and thallium (Tl) were positively associated with the risk of developing T2D, whereas the serum concentrations of manganese (Mn), molybdenum (Mo), barium (Ba), lutetium (Lu), and lead (Pb) were negatively associated with the risk of developing T2D. After adding these eight metals, the predictive ability increased significantly compared with that of the traditional clinical model (AUC: 0.791 vs. 0.772, P=8.85×10−5). In the nested casecontrol study, a machine learning analysis revealed that the serum concentrations of 14 out of 1579 detected metabolites were associated with the risk of developing T2D. According to generalized linear regression models, 7 of these metabolites were significantly associated with the serum concentrations of the identified metals. The mediation analysis showed that two metabolites (2-methyl-1,2-dihydrophthalazin-1-one and mestranol) mediated 46.81% and 58.70%, respectively, of the association between the serum Pb concentration and the risk of developing T2D. Our study suggested that serum Mn, Zn, Mo, Ba, Lu, Hg, Tl, and Pb were associated with T2D risk. Two metabolites mediated the associations between the serum Pb concentration and the risk of developing T2D.

Abstract The Caucasus region is key for understanding early human dispersal and evolution in Eurasia, and characterizing the environmental contrast between Last Glacial Maximum and Holocene is crucial for investigating human adaptation strategies to large climatic shifts. However, a paucity of high-resolution paleoclimate records leave this context largely unknown for early human populations in the Caucasus region. Based on our model-proxy comparison of high- and low-resolution records of 24 stalagmites from three caves, we find spatially distinct changes in vegetation and seasonality of precipitation, especially under glacial conditions. Supported by modern oxygen-isotope data and climate modeling, we identify a supraregional cold-season temperature control for oxygen isotopes in Black Sea speleothems, which previously had been interpreted as a local moisture-source signal. Carbon-isotope and trace-element data further suggest disproportionate changes in vegetation cover and soil dynamics at high altitudes, which would have resulted in a reduction but not a disappearance of human refugia during the Last Glacial Maximum, relative to the current interglacial. Our findings imply that abrupt climatic pressures from harsh conditions were overcome by adaptive strategies in the past.

Abstract A better understanding of the relative roles of internal climate variability and external contributions, from both natural (solar, volcanic) and anthropogenic greenhouse gas forcing, is important to better project future hydrologic changes. Changes in the evaporative demand play a central role in this context, particularly in tropical areas characterized by high precipitation seasonality, such as the tropical savannah and semi-desertic biomes. Here we present a set of geochemical proxies in speleothems from a well-ventilated cave located in central-eastern Brazil which shows that the evaporative demand is no longer being met by precipitation, leading to a hydrological deficit. A marked change in the hydrologic balance in central-eastern Brazil, caused by a severe warming trend, can be identified, starting in the 1970s. Our findings show that the current aridity has no analog over the last 720 years. A detection and attribution study indicates that this trend is mostly driven by anthropogenic forcing and cannot be explained by natural factors alone. These results reinforce the premise of a severe long-term drought in the subtropics of eastern South America that will likely be further exacerbated in the future given its apparent connection to increased greenhouse gas emissions.

Abstract Objective Traditional observational research has suggested a connection between socioeconomic position, mental health, and sleep apnea (SA), but the specifics of this connection are still unclear. Using the Mendelian randomization approach, we intended to evaluate the potential causal link between mental health, socioeconomic status, and SA. Methods Our research employed summary statistics data from large-scale genome-wide association studies (GWAS) on mental health, socioeconomic status, and SA. In the main study, the connection between mental health, socioeconomic status, and SA was examined using the inverse variance weighted approach. In addition, as a supplement, we also used other Mendelian randomization methods, including MR Egger, weighted median, simple mode, and weighted mode. Results The primary analysis showed that educational attainment, including longer years of schooling, college or university degree, and higher intelligence was associated with a lower risk of SA (OR = 0.750, 95%CI = 0.653–0.862; OR = 0.558, 95%CI = 0.423–0.735; OR = 0.871, 95%CI = 0.760–0.999, respectively), while social deprivation was associated with a higher risk of SA (OR = 1.821, 95%CI = 1.075–3.085). And the income was not associated with the risk of sleep apnea (OR = 0.877, 95%CI = 0.682–1.129). In mental health exposure, major depressive disorder was associated with a higher risk of sleep apnea (OR = 1.196, 95%CI = 1.015–1.409), while attention-deficit hyperactivity disorder, bipolar disorder, and schizophrenia were not associated with the risk of sleep apnea (OR = 1.064, 95%CI = 0.958–1.181; OR = 1.030, 95%CI = 0.942–1.127; OR = 0.990, 95%CI = 0.957–1.025, respectively). Reverse MR analysis failed to find a causal effect from SA on mental health and socioeconomic status. Conclusions This MR investigation offers proof of a possible causal relationship between SA, socioeconomic level, and mental health.

Recent years have witnessed the Open Radio Access Network (RAN) paradigm transforming the fundamental ways cellular systems are deployed, managed, and optimized. This shift is led by concepts such as openness, softwarization, programmability, interoperability, and intelligence of the network, which have emerged in wired networks through Software-defined Networking (SDN) but lag behind in cellular systems. The realization of the Open RAN vision into practical architectures, intelligent data-driven control loops, and efficient software implementations, however, is a multifaceted challenge, which requires (i) datasets to train Artificial Intelligence (AI) and Machine Learning (ML) models; (ii) facilities to test models without disrupting production networks; (iii) continuous and automated validation of the RAN software; and (iv) significant testing and integration efforts. This paper is a tutorial on how Colosseum—the world’s largest wireless network emulator with hardware in the loop—can provide the research infrastructure and tools to fill the gap between the Open RAN vision, and the deployment and commercialization of open and programmable networks. We describe how Colosseum implements an Open RAN digital twin through a high-fidelity Radio Frequency (RF) channel emulator and endto- end softwarized O-RAN and 5G-compliant protocol stacks, thus allowing users to reproduce and experiment upon topologies representative of real-world cellular deployments. Then, we detail the twinning infrastructure of Colosseum, as well as the automation pipelines for RF and protocol stack twinning. Finally, we showcase a broad range of Open RAN use cases implemented on Colosseum, including the real-time connection between the digital twin and real-world networks, and the development, prototyping, and testing of AI/ML solutions for Open RAN.

Objectives: Myasthenia Gravis (MG) is an autoimmune disorder that can exacerbate for various reasons, including vaccination and infection. This study aimed to investigate the safety of COVID-19 vaccines for MG patients, factors influencing MG exacerbation after COVID-19 infection (MECI), the course and prognosis of MECI, and the impact of COVID-19 vaccine on infected MG patients. Methods: Patients were enrolled from the MG database in the Department of Neurology, Xuanwu Hospital, Capital Medical University. Two questionnaires were administered to collect data concerning COVID-19 vaccination (questionnaire 1, Q1) and infection (questionnaire 2, Q2) during two distinct periods. MG exacerbation was defined as an increase of at least two points in the MG activity of daily living (MG-ADL) score. COVID-19 severity was categorized as “hospitalization” or “home management”; Results: During the first data-collecting period, our database registered 1013 adult patients: 273 (26.9%) had received COVID-19 vaccinations and completed Q1, and 8 (2.9%) experienced MG exacerbation after vaccination. During the second data-collecting period, among the newly registered patients, 366 patients completed Q2. Of these, 244 were infected, with 39 (16.0%) experiencing MECI and 21 (8.6%) requiring hospitalization. Multivariate analysis showed that generalized myasthenia gravis was associated with MECI (OR 3.354, 95% CI: 1.423–7.908, p = 0.006). Among the 244 infected patients, 143 had received COVID-19 vaccinations, including 14 who received their booster dose within 6 months before COVID-19 and 129 who were vaccinated more than 6 months before COVID-19. The remaining 101 were unvaccinated. No significant associations were found between COVID-19 vaccination and COVID-19 severity (p = 0.292) or MECI incidence (p = 0.478); Conclusions: COVID-19 vaccines were found to be safe for MG patients in stable condition. Patients with gMG were more susceptible to experiencing MECI. No significant impact of the vaccine on COVID-19 severity or MECI incidence was observed.

Abstract Background Paranasal sinus angiosarcoma is an uncommon malignancy, with only a few reported cases worldwide. Although it exhibits multiple symptoms, facial paralysis has not been previously documented as a noticeable presentation. Case Presentation In this case, we report a 40-year-old male who presented with facial numbness and pain for one month, weakness of his facial muscles for 15 days, and recurrent right epistaxis for 1 year. He had a history of nasal inflammatory polyps with chronic sinusitis. Computed tomography and magnetic resonance imaging showed space-occupying lesions in the right nasal cavity and maxillary sinus, with bone destruction occurring in the sinus wall and turbinate. This patient then underwent endoscopic surgery. According to the histopathological and immunohistochemical results, he was eventually diagnosed with paranasal sinus angiosarcoma in April 2021. To date, this patient has not initiated any radiotherapy or chemotherapy and has survived with lymphatic metastasis for at least 3 years. Conclusions This manuscript suggests that paranasal sinus angiosarcoma can present with facial paralysis. Moreover, pathological and immunohistochemical tests are still vital for diagnosing paranasal sinus angiosarcoma and differential diagnosis. Additionally, regular follow-up is crucial for patients with paranasal sinus angiosarcoma, enabling monitoring of recurrence, metastasis, and recovery while contributing valuable clinical data to understanding this rare disease and associated research endeavours.

Abstract How often have past climates undergone abrupt transitions? While our understanding of millennial variability during the past 130,000 years is well established, with precise dates available, such information on previous climate cycles is limited. To address this question, we identified 196 abrupt transitions in the δ18O record of the well-dated Chinese composite speleothem for the last 640,000 years. These results correspond to abrupt changes in the strength of the East Asian Monsoon, which align with the Greenland stadials and interstadials observed in the North Atlantic region during the last 130,000 years before present. These precise dates of past abrupt climate changes constitute a reliable and necessary benchmark for Earth System models used to study future climate scenarios.

Abstract Characterization of moisture origins is crucial to understanding hydroclimatic processes. Nevertheless, documenting past atmospheric moisture contents and their sources remains challenging partially due to insufficient moisture-tracing proxies. Here, we present triple oxygen isotope compositions in 21 cave speleothems from monsoonal Asia to examine spatial moisture origin differences in eastern Asia over the past 300 years. Our data suggest an isotopic equilibrium fractionation during speleothem formation, and thus parent water 17O anomalies (Δ′17O) values reconstructed from speleothems preserve information on moisture origins and recycling across space. Notably, speleothem Δ′17O records exhibit a distinct geographical distribution, with low values in central-eastern and southern China, high values in northwestern and northern China, and relatively high values in the Yangtze River region. This spatial pattern underscores the diverse influence of different moisture sources regulated by regional hydrological circulation, and demonstrates the potential use of speleothem Δ′17O in reconstructing the moisture cycle at spatial scales.

Abstract Qunf Cave oxygen isotope (δ18Oc) record from southern Oman is one of the most significant of few Holocene Indian summer monsoon cave records. However, the interpretation of the Qunf δ18Oc remains in dispute. Here we provide a multi-proxy record from Qunf Cave and climate model simulations to reconstruct the Holocene local and regional hydroclimate changes. The results indicate that besides the Indian summer monsoon, the North African summer monsoon also contributes water vapor to southern Oman during the early to middle Holocene. In principle, Qunf δ18Oc values reflect integrated oxygen-isotope fractionations over a broad moisture transport swath from moisture sources to the cave site, rather than local precipitation amount alone, and thus the Qunf δ18Oc record characterizes primary changes in the Afro-Asian monsoon regime across the Holocene. In contrast, local climate proxies appear to suggest an overall slightly increased or unchanged wetness over the Holocene at the cave site.

Abstract Chronic pain is often associated with cognitive decline, which could influence the quality of the patient’s life. Recent studies have suggested that Toll-like receptor 3 (TLR3) is crucial for memory and learning. Nonetheless, the contribution of TLR3 to the pathogenesis of cognitive decline after chronic pain remains unclear. The level of TLR3 in hippocampal neurons increased in the chronic constriction injury (CCI) group than in the sham group in this study. Importantly, compared to the wild-type (WT) mice, TLR3 knockout (KO) mice and TLR3-specific neuronal knockdown mice both displayed improved cognitive function, reduced levels of inflammatory cytokines and neuronal apoptosis and attenuated injury to hippocampal neuroplasticity. Notably, extracellular RNAs (exRNAs), specifically double-stranded RNAs (dsRNAs), were increased in the sciatic nerve, serum, and hippocampus after CCI. The co-localization of dsRNA with TLR3 was also increased in hippocampal neurons. And the administration of poly (I:C), a dsRNA analog, elevated the levels of dsRNAs and TLR3 in the hippocampus, exacerbating hippocampus-dependent memory. In additon, the dsRNA/TLR3 inhibitor improved cognitive function after CCI. Together, our findings suggested that exRNAs, particularly dsRNAs, that were present in the condition of chronic neuropathic pain, activated TLR3, initiated downstream inflammatory and apoptotic signaling, caused damage to synaptic plasticity, and contributed to the etiology of cognitive impairment after chronic neuropathic pain.

Understanding the relationship between tree growth and environmental conditions is essential to elucidating the impact of global climate change on forest ecosystems. We used the dendrochronology method to examine the growth sensitivity of a typical conifer to climate change in mountain forests of Central Hengduan Mountain. The study involved the establishment of tree ring width chronologies of Pinus yunnanensis in both Haba Snow Mountain (HB) and Yulong Snow Mountain (YL) in northwestern Yunnan, enabling the detection of the relationship between its radial growth and climates, i.e., monthly total precipitation, monthly temperatures (average minimum, mean and maximum) and monthly Palmer Drought Severity Index (PDSI). Response function and redundancy analysis (RDA) were used to identify correlations between climate variables and radial growth, and moving interval analysis was applied to determine the stability of climate-growth relationship. The findings demonstrated that the growth of P. yunnanensis had similar response patterns to climate change at two sites, exhibiting growth synchronization and common signals. Specifically, the radial growth of P. yunnanensis was negatively correlated with May temperature, while temperature in current October significantly promoted radial growth. Precipitation in June was the common climate variable with inverse effects between two sites, with positive impacts on YL and negative impacts on HB. The results of moving interval analysis were consistent with response function and RDA, presenting significant correlations in many years for those climatic variables significantly affecting tree growth. Stability analysis also revealed that the climate-growth relationship could fluctuate over a small range of time scales, induced by an abrupt change in climate. A forecast of strengthen in growth of P. yunnanensis forests was expected, since increases in precipitation and temperature of most months would benefit tree growth, and negative impacts of May temperature would be offset by the increase of precipitation in the corresponding month. These results could provide a basis for developing sustainable strategies of forest management under the climate change.

Betanin, a water-soluble colorant, is sensitive to light and temperature and is easily faded and inactivated. This study investigated the formation of yeast protein-chitooligosaccharide-betanin complex (YCB) induced by ultrasound treatment, and evaluated its protective effect on the colorant betanin. Ultrasound (200–600 W) increased the surface hydrophobicity and solubility of yeast protein, and influenced the protein’s secondary structure by decreasing the α-helix content and increasing the contents of β-sheet and random coil. The ultrasound treatment (200 W, 15 min) facilitated binding of chitooligosaccharide and betanin to the protein, with the binding numbers of 4.26 ± 0.51 and 0.61 ± 0.06, and the binding constant of (2.73 ± 0.25) × 105 M−1 and (3.92 ± 0.10) × 104 M−1, respectively. YCB could remain the typical color of betanin, and led to a smaller and disordered granule morphology. Moreover, YCB exhibited enhanced thermal-, light-, and metal irons (ferric and copper ions) -stabilities of betanin, protected the betanin against color fading, and realized a controlled release in simulated gastrointestinal tract. This study extends the potential application of the fungal proteins for stabilizing bioactive molecules.

Effectively identifying and managing the priority regulation areas (PRAs) of ecosystem services (ESs) are very important for improving the supply–demand relationship (SDR) of ESs and promoting regional sustainable development. Based on the InVEST model, geographic information system (GIS) spatial analysis and statistical methods, this study assessed the supply and demand of five types of ESs in the Loess Plateau from 2000 to 2020, namely, water yield, food supply, carbon storage, soil conservation and recreation. The quantitative and spatial relationships between the supply and demand were analyzed, and the PRA with a severe imbalance between ES supply and demand was identified. According to the regulation index, the importance of different types of PRAs was identified. Then, the potential constraints of the trade-off and synergy on the regulation of the SDR were discussed, and specific regulation suggestions were proposed. The results showed that from 2000 to 2020, the supply and demand of the five types of ESs on the Loess Plateau increased except for water demand, and the spatial distribution was mostly low in the northwest and high in the southeast, or low in the center surrounded by high values. The degree of surplus of recreation in the study area decreased, while that of the other types of ESs increased. Regarding carbon storage and recreation, the high supply–low demand clustering areas were the largest; regarding the other types of ESs, the low supply–low demand clustering areas were the largest. The low supply-low demand clustering areas for water yield, carbon storage, and soil conservation showing a spatial trend of narrowing to the northwest. The PRAs are mostly high-demand deficit areas, and there are various types. In each province, the areas where there is no overlap in the PRAs for specific type of ES has the highest priority of regulation. For the areas where the PRAs of several types of ESs overlap, targeted regulation measures need to be formulated in combination with the trade-offs and synergies between SDRs.

Accurately grasping the spatial network correlation structure of operational efficiency in star-rated hotels and its influencing factors is of great significance for promoting high-quality coordinated development of star-rated hotels and the regional tourism reception industry. Using a comprehensive approach integrating the Super-DEA model, modified gravity model, and social network analysis to explore the evolving characteristics of spatial network structure in operational efficiency of provincial star-rated hotels in China from 2013 to 2022, and their underlying mechanisms. The results indicate that: (1) During the study period, the average operational efficiency of star-rated hotels in China was 0.618, with spatial efficiency values showing a distribution pattern of "Eastern > Central > Western > Northeastern". (2) The spatial correlation network of operational efficiency among provincial star-rated hotels in China overall exhibits characteristics of densification, hierarchical structure, and reinforcement. Provinces such as Beijing, Tianjin, Shanghai, and Jiangsu in the eastern region play central roles as "central actors" in the network, while provinces in the western and northeastern regions such as Heilongjiang, Tibet, and Xinjiang play roles as "passive actors" in the spatial network. (3) Members of the "Net benefit" and "Two-way spillover" are primarily from the eastern and some central provinces, while members of the "Net overflow" are mainly from the northeastern and western provinces. (4) Factors such as economic development level, residents' consumption level, and distance from provincial capital cities collectively drive the evolution and optimization of the spatial network structure of operational efficiency among provincial star-rated hotels in China. This study not only enriches the research findings on hotel operational efficiency but also provides a reference for constructing a cross-regional collaborative mechanism to enhance the operational efficiency of star-rated hotels.

Sulfate corrosion is one of the main causes of tunnel lining deterioration. An accurate understanding of the damage characteristics and corrosion mechanism of sulfate-corroded tunnels is the basis for the anti-corrosion design and damage control of the tunnel lining. Based on a project concerning a sulfate-corroded tunnel in the mountainous area of Southwest China, this study conducted a field investigation and laboratory tests and, combined with existing research data, summarized the damage characteristics and corrosion mechanism of this type of tunnel and proposed the characteristic corrosion state of tunnel lining in a sulfate environment. The results show that 1) sulfate corrosion led to leakage, surface spalling crystallization, and strength loss, and the corrosion typically occurred at the arch waist and arch foot. 2) Physical and chemical corrosion occurred in the tunnel lining, and the corrosion products included sodium sulfate, calcium carbonate, gypsum, ettringite, and thaumasite. 3) In China, this type of tunnel is mainly located in the Southwest and Northwest, and its lining is in a special state of “one-sided accelerated corrosion.”

Structural planes decrease the strength and stability of rock masses, severely affecting their mechanical properties and deformation and failure characteristics. Therefore, investigation and analysis of structural planes are crucial tasks in mining rock mechanics. The drilling camera obtains image information of deep structural planes of rock masses through high-definition camera methods, providing important data sources for the analysis of deep structural planes of rock masses. This paper addresses the problems of high workload, low efficiency, high subjectivity, and poor accuracy brought about by manual processing based on current borehole image analysis and conducts an intelligent segmentation study of borehole image structural planes based on the U2-Net network. By collecting data from 20 different borehole images in different lithological regions, a dataset consisting of 1,013 borehole images with structural plane type, lithology, and color was established. Data augmentation methods such as image flipping, color jittering, blurring, and mixup were applied to expand the dataset to 12,421 images, meeting the requirements for deep network training data. Based on the PyTorch deep learning framework, the initial U2-Net network weights were set, the learning rate was set to 0.001, the training batch was 4, and the Adam optimizer adaptively adjusted the learning rate during the training process. A dedicated network model for segmenting structural planes was obtained, and the model achieved a maximum F-measure value of 0.749 when the confidence threshold was set to 0.7, with an accuracy rate of up to 0.85 within the range of recall rate greater than 0.5. Overall, the model has high accuracy for segmenting structural planes and very low mean absolute error, indicating good segmentation accuracy and certain generalization of the network. The research method in this paper can serve as a reference for the study of intelligent identification of structural planes in borehole images.

Abstract Speleothem δ18O is widely used as a proxy for rainfall amount in the tropics on glacial-interglacial to interannual scales. However, uncertainties in the interpretation of this renowned proxy pose a vexing problem in tropical paleoclimatology. Here, we present paired multi-proxy geochemical measurements for stalagmites from southwest Sulawesi, Indonesia, and confirm changes in rainfall amount across ice age terminations. Collectively, the stalagmites span two glacial-interglacial transitions from ~380,000 to 330,000 and 230,000 to 170,000 years ago. Mg/Ca in the slow-growing stalagmites is affected by water moving through the karst and prior calcite precipitation, making it a good proxy for changes in local rainfall. When paired, Mg/Ca and δ18O corroborate prominent shifts from drier glacials to wetter interglacials in the core of the Australasian monsoon domain. These shifts in rainfall occur 4,000-7,000 years later than glacial-interglacial increases in global temperature and the associated response of Sulawesi vegetation, determined by speleothem δ13C.

Abstract Background and objective The pathogenesis and pathophysiology of idiopathic normal pressure hydrocephalus (iNPH) remain unclear. Homocysteine may reduce the compliance of intracranial arteries and damage the endothelial function of the blood-brain barrier (BBB), which may be the underlying mechanism of iNPH. The overlap cases between deep perforating arteriopathy (DPA) and iNPH were not rare for the shared risk factors. We aimed to investigate the relationship between serum homocysteine and iNPH in DPA. Methods A total of 41 DPA patients with iNPH and 49 DPA patients without iNPH were included. Demographic characteristics, vascular risk factors, laboratory results, and neuroimaging data were collected. Multivariable logistic regression analysis was performed to investigate the relationship between serum homocysteine and iNPH in DPA patients. Results Patients with iNPH had significantly higher homocysteine levels than those without iNPH (median, 16.34 mmol/L versus 14.28 mmol/L; P = 0.002). There was no significant difference in CSVD burden scores between patients with iNPH and patients without iNPH. Univariate logistic regression analysis demonstrated that patients with homocysteine levels in the Tertile3 were more likely to have iNPH than those in the Tertile1 (OR, 4.929; 95% CI, 1.612–15.071; P = 0.005). The association remained significant after multivariable adjustment for potential confounders, including age, male, hypertension, diabetes mellitus, atherosclerotic cardiovascular disease (ASCVD) or hypercholesterolemia, and eGFR level. Conclusion Our study indicated that high serum homocysteine levels were independently associated with iNPH in DPA. However, further research is needed to determine the predictive value of homocysteine and to confirm the underlying mechanism between homocysteine and iNPH.

Abstract There is a general agreement that Northern Hemisphere temperatures have cooled over the past two millennia, culminating in the Little Ice Age. However, this understanding partly relies on the compilation of existing proxy records, the majority of which carry a warm season bias such that there is an underrepresentation of cold-season temperatures. Here we report a unique cold-season temperature record based on the alkenone paleothermometer from the northeastern Tibetan Plateau that spans the last two millennia. In contrast to the regional- and hemisphere-scale summer cooling, our reconstruction shows a long-term warming through the Medieval Climate Anomaly into Little Ice Age. We attribute these opposing temperature trends to combined effects of seasonally divergent insolation and North Atlantic subpolar gyre circulation. Our study indicates that the cold season during the Little Ice Age was not the coldest period of the last two millennia at least on the northeastern Tibetan Plateau.