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Abstract Although some studies have explored the role of meteorological factors in the development of tuberculosis (TB), the majority have been confined to single regions, leading to inconsistent findings. Consequently, we conducted a multi-city study not only to determine whether meteorological factors significantly influence the risk of developing TB but also to assess the magnitude of these effects and explore potential modifying factors. Data on daily reported TB cases and meteorological factors were collected from January 1, 2013, to December 31, 2022, across 11 cities in Zhejiang Province. A distributed lag non-linear model using a quasi-Poisson distribution was employed. Multivariate meta-regression was used to obtain overall pooled estimates and assess heterogeneity. From 2013 to 2022, 267,932 TB cases were reported in Zhejiang Province. Notably, a nonlinear relationship was observed between temperature and TB, with the relative risk (RR) peaking at 1.0 °C (RR = 1.882, 95% CI 1.173–3.020). The effect of low temperature was immediate and significant for a 13-day lag period, with the maximum effect at lag0 (RR = 1.014, 95% CI 1.008–1.021). The exposure-response curve between relative humidity (RH) and TB exhibited an M-shape, with the RR peaking at 47.7% (RR = 1.642, 95% CI 1.044–2.582). The lag effect of low RH was significant at lag 25–59, with the highest RR observed at lag 32 (RR = 1.011, 95% CI 1.001–1.022). Gross domestic product (GDP) per person, population density, and latitude demonstrated significant modification effects. Our study showed that low temperature and RH were associated with an increased risk of TB. Additionally, GDP per person, population density, and latitude may play important roles in explaining the association between RH and TB. These findings provide scientific evidence for the development of geographically specific public health policies.

Abstract Novel neoadjuvant immunotherapy combined with chemotherapy (neoICT) has improved outcomes for patients with esophageal squamous-cell carcinoma (ESCC), but challenges persist in low response rates and therapy resistance. Little is known about the intra-tumoral heterogeneity in the ESCC tumor microenvironment (TME) that underlies differential responses to neoadjuvant therapy. We applied single-cell RNA sequencing (scRNA-seq) profiling and multiplexed immunofluorescence staining to thoroughly decipher the TME in ESCC specimens from a neoadjuvant anti-PD1 combination therapy clinical trial. The cancer-associated fibroblasts (CAFs) population showed the significant alteration in abundance following neoadjuvant therapy. Specifically, IL6 + CCL2 + immunomodulatory CAFs and a novel CD248 + mechanoresponsive CAFs subset exhibited increasing infiltration. Mechanistically, CD248 + mechanoresponsive CAFs approached and lined the tumor nest to physically block the infiltration of CD8 + T cells and drug delivery, while IL6 + CCL2 + immunomodulatory CAFs induced therapeutic resistance with distinct IL-6 expression. Among patients treated with neoICT, we observed prominent CAF-T cell interactions. In particular, the NECTIN2-TIGIT ligand-receptor pair was enriched in treated samples, and TIGIT was identified as the major inhibitory checkpoint of T cells. Our findings demonstrate distinct alterations in TME constituent responses to neoadjuvant immunotherapy and identify functional phenotypes of CAFs associated with unfavorable therapeutic responses in patients. This provides potential targets to enhance responses to neoadjuvant therapy in ESCC.

Abstract The spatial delays of pulmonary tuberculosis (PTB) have been less explored. In this study, a total of 151,799 notified PTB cases were included, with median patient and diagnostic delays of 15 [interquartile range (IOR), 4–35] and 2 (IOR, 0–8) days, respectively. The spatial autocorrelation analysis and spatial–temporal scan statistics were used to determine the clusters, indicating that the regions in the southwestern and northeastern parts of Zhejiang Province exhibited high rates of long-term patient delay (LPD, delay ≥ 15 days) and long-term diagnostic delay (LDD, delay ≥ 2 days). Besides, the Mantel test indicated a moderately positive correlation between public awareness of suspicious symptoms and the LPD rate in 2018 (Mantel's r = 0.4, P

Abstract Histone lysine crotonylation, an evolutionarily conserved modification differing from acetylation, exerts pivotal control over diverse biological processes. Among these are gene transcriptional regulation, spermatogenesis, and cell cycle processes. However, the dynamic changes and functions of histone crotonylation in preimplantation embryonic development in mammals remain unclear. Here, we show that the transcription coactivator P300 functions as a writer of histone crotonylation during embryonic development. Depletion of P300 results in significant developmental defects and dysregulation of the transcriptome of embryos. Importantly, we demonstrate that P300 catalyzes the crotonylation of histone, directly stimulating transcription and regulating gene expression, thereby ensuring successful progression of embryo development up to the blastocyst stage. Moreover, the modification of histone H3 lysine 18 crotonylation (H3K18cr) is primarily localized to active promoter regions. This modification serves as a distinctive epigenetic indicator of crucial transcriptional regulators, facilitating the activation of gene transcription. Together, our results propose a model wherein P300-mediated histone crotonylation plays a crucial role in regulating the fate of embryonic development.

Abstract We conducted a retrospective study to investigate risk factors for tuberculosis care-seeking delay and diagnostic delays among pediatric pulmonary tuberculosis cases in Zhejiang Province from 2013 to 2022. Among 1274 cases, 49.61% experienced tuberculosis care-seeking delays (> 14 days from symptom onset to first hospital visit) and 14.91% faced diagnostic delays (> 14 days from initial consultation to diagnosis). The proportion of care-seeking delays ranged from 37.42 to 64.89%, while diagnostic delay fluctuated from 6.11 to 21.02%. Urban residence (OR = 0.78, 95% CI 0.62–0.98, P = 0.030), first visiting a municipal-level hospital (OR = 0.57, 95% CI 0.45–0.72, P

Abstract Background Blended learning comprised with flipped classroom (FC) and “internet plus” is a new learning strategy that reverses the position of teacher and students in class, and provides abundant learning resources before and after class. This study aimed to assess the impact of blended learning on learning outcomes in evidence-based medicine course, and compare with traditional learning method. Methods The participants of the two groups were from two difference cohorts in Air force medical university in China. The two groups toke the same pre-test before class and then were given the teaching of same chapters of evidence-based medicine with two different learning strategy. In the blended learning group, the participants were required to create a debriefing slide about their learning outcomes and the answers of questions given in advance after study the learning material sent by teacher a week before class, and the teacher gave a detailed summary based on the common problems, and distributed multimedia resources for review. After the experiment was carried out, learning outcomes including mastering knowledge, learning satisfaction, and self-evaluation were compared. Results 37 and 39 participants were enrolled to blended learning and traditional learning groups, respectively, and no statistically significant difference were found in baseline information and pre-test grades. Statistically significant differences were found in learning outcomes including post-test score (t = 2.90, p = 0.005), changes of scores between pre-test and post-test (t = 2.49, p = 0.022), learning satisfaction (t = 12.41, p = 0.001), and self-evaluation of the two groups (t = 7.82, p = 0.001). Especially, the changes of scores between pre-test and post-test of blended learning and traditional learning groups were 4.05 (4.26), and 2.00 (2.85), respectively. Conclusions This study showed that compared with traditional learning strategy, blended learning can effectively enhanced participants’ acquisition of knowledge, learning satisfaction, and self-evaluation in evidence-based medicine. Using blended learning method including “internet plus” and flipped classroom is recommended in the teaching of evidence-based medicine course.

IntroductionThe mechanisms leading to ovarian primordial follicle depletion following gonadotoxic chemotherapy with cyclophosphamide and other cytotoxic drugs are currently understood through two main explanatory theories: apoptosis and over-activation. Discrepancies between the findings of different studies investigating these mechanisms do not allow to reach a firm conclusion. The heterogeneity of cell types in ovaries and their different degrees of sensitivity to damage, cell-cell interactions, periodical follicle profile differences, model age-dependent differences, and differences of exposure durations of tested drugs may partially explain the discrepancies among studies.MethodsThis study used intact prepubertal mice ovaries in culture as study model, in which most follicles are primordial follicles. Histological and transcriptional analyses of ovaries exposed to the active metabolite of cyclophosphamide 4-hydroperoxycyclophosphamide (4-HC) were carried out via a time-course experiment at 8, 24, 48, and 72 h.Results4-HC treated ovaries showed a significant decrease in primordial follicle density at 24 h, along with active DNA damage (TUNEL) and overexpressed apoptosis signals (cleaved-poly ADP ribose polymerase in immunohistochemistry and western blotting). Meanwhile 4-HC treatment significantly up-regulated H2ax, Casp 6, Casp 8, Noxa, and Bax in ovaries, and up-regulated Puma in primordial follicles (FISH).DiscussionOur results indicated that cyclophosphamide-induced acute ovarian primordial follicle depletion was mainly related to apoptotic pathways. No evidence of follicle activation was found, neither through changes in the expression of related genes to follicle activation nor in the density of growing follicles. Further validation at protein level in 4-HC-treated prepubertal mice ovaries at 24 h confirmed these observations.

Objective: To study the effects of astragalus polysaccharide (APS) on aplastic anaemia (AA) in mice through modulation of the upstream and downstream effectors of the Hippo pathway. Further, we investigated the underlying mechanisms of APS in the treatment of AA to provide possible therapeutic strategies and drugs for clinical use. Methods: BALB/c mice were subjected to 4 Gy X-ray irradiation and subsequently injected with lymphocytes from DBA/2 donor mice by using the tail vein to establish an AA mouse model. Next BALB/c mice were randomly divided into five groups: control (untreated), AA (model), and three APS remedy groups - LA (low-dose APS, 200 mg/kg), MA (medium-dose APS, 400 mg/kg), and HA (high-dose APS, 800 mg/kg). The mice were sacrificed after 14 d of continuous gavage with different doses of APS or saline, and the bone marrow, spleen and liver were obtained. The haematopoietic condition, apoptosis levels, and the expression of Large Tumour Suppressor 1/2 (LATS 1/2), transcriptional co-activator of activation (TCA) Yes-associated protein (YesAP), transcriptional enhancer of adherence domain (TEAD) protein, and Telomerase Reverse Transcriptase (TERT), were analysed. Results: Compared with control mice, mice in the AA group exhibited a reduction in peripheral blood cell counts, a significant decrease in the haematopoietic area, increased adipocyte infiltration, and overall haematopoietic failure, mirroring the clinical presentation of AA; After 14 days of treatment with different doses of APS, the APS-treated group, in comparison to the untreated AA group, showed an increase in peripheral blood cell counts (P

ObjectiveTo understand and analyze the factors relating to patient and diagnostic delays among groups with tuberculous pleurisy (TP), and its spatiotemporal distribution in Zhejiang Province.MethodsData of all tuberculous pleurisy patients were collected from the existing Tuberculosis Information Management System. A time interval of > 2 weeks between first symptom onset and visit to the designated hospital was considered a patient delay, and a time interval of > 2 weeks between the first visit and a confirmed TP diagnosis was considered a diagnostic delay. Univariate and multivariate logistic regression analyses were used to explore factors influencing patient and diagnostic delays in patients with TP. Spatial autocorrelation and spatiotemporal scan analyses were used to identify hot spots and risk clusters, respectively.ResultsIn total, 10,044 patients with TP were included. The median time and interquartile range for patients seeking medical care and diagnosis were 15 (7–30) and 1 (0–8) days, respectively. The results showed that people aged > 65 years, retirees, and residents of Jinhua, Lishui, and Quzhou were positively correlated with patient delay, whereas retreatment patients, houseworkers, unemployed people, and residents of Zhoushan or Ningbo were positively correlated with diagnostic delay. Additionally, high-risk clusters of patient delays were observed in the midwestern Zhejiang Province. The most likely clusters of TP diagnostic delays were found in southeast Zhejiang Province.ConclusionIn summary, patient delay of TP in Zhejiang province was shorter than for pulmonary tuberculosis in China, while the diagnostic delay had no difference. Age, city, occupation, and treatment history were related to both patient and diagnostic delays in TP. Interventions in central and western regions of Zhejiang Province should be initiated to improve the early detection of TP. Additionally, the allocation of health resources and accessibility of health services should be improved in the central and eastern regions of Zhejiang Province.

Abstract Aphanomyces euteiches causes root rot in pea, leading to significant yield losses. However, the metabolites involved in this pathosystem have not been thoroughly studied. This study aimed to fill this gap and explore mechanisms of bacterial suppression of A. euteiches via untargeted metabolomics using pea grown in a controlled environment. Chemical isotope labeling (CIL), followed by liquid chromatography-mass spectrometry (LC–MS), was used for metabolite separation and detection. Univariate and multivariate analyses showed clear separation of metabolites from pathogen-treated pea roots and roots from other treatments. A three-tier approach positively or putatively identified 5249 peak pairs or metabolites. Of these, 403 were positively identified in tier 1; 940 were putatively identified with high confidence in tier 2. There were substantial changes in amino acid pool, and fatty acid and phenylpropanoid pathway products. More metabolites, including salicylic and jasmonic acids, were upregulated than downregulated in A. euteiches-infected roots. 1-aminocyclopropane-1-carboxylic acid and 12-oxophytodienoic acid were upregulated in A. euteiches + bacterium-treated roots compared to A. euteiches-infected roots. A great number of metabolites were up- or down-regulated in response to A. euteiches infection compared with the control and A. euteiches + bacterium-treated plants. The results of this study could facilitate improved disease management.

Abstract Brain metastasis (BM) is one of the leading causes of cancer-related deaths in patients with advanced non-small cell lung cancer (NSCLC). However, limited treatments are available due to the presence of the blood-brain barrier (BBB). Upregulation of lysophosphatidylcholine acyltransferase 1 (LPCAT1) in NSCLC has been found to promote BM. Conversely, downregulating LPCAT1 significantly suppresses the proliferation and metastasis of lung cancer cells. In this study, we firstly confirmed significant upregulation of LPCAT1 in BM sites compared to primary lung cancer by analyzing scRNA dataset. We then designed a delivery system based on a single-chain variable fragment (scFv) targeting the epidermal growth factor receptor (EGFR) and exosomes derived from HEK293T cells to enhance cell-targeting capabilities and increase permeability. Next, we loaded LPCAT1 siRNA (siLPCAT1) into these engineered exosomes (exoscFv). This novel scFv-mounted exosome successfully crossed the BBB in an animal model and delivered siLPCAT1 to the BM site. Silencing LPCAT1 efficiently arrested tumor growth and inhibited malignant progression of BM in vivo without detectable toxicity. Overall, we provided a potential platform based on exosomes for RNA interference (RNAi) therapy in lung cancer BM.

Background Several studies have suggested an association between vitamin deficiency and the development of tuberculosis; however, the precise impact remains unclear. This study aimed to elucidate the relationship between distinct vitamin statuses and the occurrence of tuberculosis.Materials and methods Retrieval was conducted using several databases without language restrictions to capture the eligible studies on tuberculosis and vitamin status. Pooled odds ratios (ORs), relative risks (RRs), and hazard ratios (HRs) were used with 95% confidence intervals (CIs) to clarify the relationship between the different vitamin statuses (A, B, D, and E) and the occurrence of tuberculosis. Subgroup analysis, sensitivity analysis, meta-regression analysis, and Galbraith plot were performed to determine sources of heterogeneity. Potential publication biases were detected using Begg’s test, Egger’s test, and the trim-and-fill test.Results We identified 10,266 original records from our database searches, and 69 eligible studies were considered in this study. The random-effect model showed that people with tuberculosis may exhibit vitamin A deficiency (OR = 10.66, 95%CI: 2.61–43.63, p = .001), while limited cohort studies showed that vitamin A supplementation may reduce tuberculosis occurrence. Additionally, vitamin D deficiency was identified as a risk factor for tuberculosis development (RR = 1.69, 95%CI: 1.06–2.67, p = .026), and people with tuberculosis generally had lower vitamin D levels (OR = 2.19, 95%CI: 1.76–2.73, p

Abstract Background In many areas of China, over 30% of tuberculosis cases occur among the elderly. We aimed to investigate the spatial distribution and environmental factors that predicted the occurence of tuberculosis in this group. Methods Data were collected on notified pulmonary tuberculosis (PTB) cases aged ≥ 65 years in Zhejiang Province from 2010 to 2021. We performed spatial autocorrelation and spatial-temporal scan statistics to determine the clusters of epidemics. Spatial Durbin Model (SDM) analysis was used to identify significant environmental factors and their spatial spillover effects. Results 77,405 cases of PTB among the elderly were notified, showing a decreasing trend in the notification rate. Spatial-temporal analysis showed clustering of epidemics in the western area of Zhejiang Province. The results of the SDM indicated that a one-unit increase in PM2.5 led to a 0.396% increase in the local notification rate. The annual mean temperature and precipitation had direct effects and spatial spillover effects on the rate, while complexity of the shape of the greenspace (SHAPE_AM) and SO2 had negative spatial spillover effects. Conclusion Targeted interventions among the elderly in Western Zhejiang may be more efficient than broad, province-wide interventions. Low annual mean temperature and high annual mean precipitation in local and neighboring areas tend to have higher PTB onset among the elderly.

Herein, the sintering behavior and dielectric properties of Ta5+-doped Li3Mg4NbO8 ceramics were investigated by solid-phase reactions in combination with first-principles calculations. In particular, Li3Mg4Nb0.96Ta0.04O8 illustrates the best dielectric properties after sintering at 1,175 °C with εr = 13.71 ± 0.20, Q × f = (132,112 ± 2,391) GHz (increased by 25%) and τf = (25.07 ± 1.36) × 10−6 °C−1. The non-intrinsic factors reflect that a small amount of Ta5+ doping produces a secondary phase, increased densification, and grain size, all of which optimize the dielectric properties. The dominant intrinsic factors indicate that the increase in bond ionicity, the greater polarization of Ta5+, and the blueshift of the Raman characteristic peak all lead to an increase in εr. The increase in lattice energy and the decrease in the damping behavior of the Nb/Ta-O bond vibrations lead to an increase in Q × f. The weakening of the Nb/TaO6 octahedral distortion leads to an optimization of τf. The modified Li3Mg4Nb0.96Ta0.04O8 ceramics have promising applications in microwave communications.

Background: The COVID-19 pandemic has had a profound global impact, although the majority of recently infected cases have presented with mild to moderate symptoms. Previous clinical studies have demonstrated that Shufeng Jiedu (SFJD) capsule, a Chinese herbal patent medicine, effectively alleviates symptoms associated with the common cold, H1N1 influenza, and COVID-19. This study aimed to assess the efficacy and safety of SFJD capsules in managing symptoms of mild to moderate COVID-19 infection.Methods: A randomized, double-blind, placebo-controlled trial was conducted from May to December 2022 at two hospitals in China. Mild and moderate COVID-19-infected patients presenting respiratory symptoms within 3 days from onset were randomly assigned to either the SFJD or placebo groups in a 1:1 ratio. Individuals received SFJD capsules or a placebo three times daily for five consecutive days. Participants were followed up for more than 14 days after their RT-PCR nucleoid acid test for SARS-CoV-2 turned negative. The primary outcome measure was time to alleviate COVID-19 symptoms from baseline until the end of follow-up.Results: A total of 478 participants were screened; ultimately, 407 completed the trial after randomization (SFJD, n = 203; placebo, n = 204). No statistically significant difference in baseline parameters was observed between the two groups. The median time to alleviate all symptoms was 7 days in the SFJD group compared to 8 days in the placebo group (p = 0.037). Notably, the SFJD group significantly attenuated fever/chills (p = 0.04) and headache (p = 0.016) compared to the placebo group. Furthermore, the median time taken to reach normal body temperature within 24 h was reduced by 7 hours in the SFJD group compared to the placebo group (p = 0.033). No deaths or instances of serious or critical conditions occurred during this trial period; moreover, no serious adverse events were reported.Conclusion: The trial was conducted in a unique controlled hospital setting, and the 5-day treatment with SFJD capsules resulted in a 1-day reduction in overall symptoms, particularly headache and fever/chills, among COVID-19-infected participants with mild or moderate symptoms. Compared to placebo, SFJD capsules were found to be safe with fewer side effects. SFJD capsules could potentially serve as an effective treatment for alleviating mild to moderate symptoms of COVID-19.Clinical Trial Registration: https://www.isrctn.com/, identifier ISRCTN14236594.

IntroductionChronic obstructive pulmonary disease (COPD) is a chronic respiratory disease with high prevalence and mortality. In some acute exacerbations of COPD (AECOPD) in patients with no obvious signs of infection, early antibiotic treatment seems to clinically improve the disease, but more studies are needed to determine the prognostic impact of antibiotic treatment in AECOPD patients with no obvious signs of infection.PurposeTo clarify the impact of antibiotic treatment on the short-term and long-term prognoses of AECOPD patients without obvious signs of infection.MethodsThe impact of the two treatment methods on the prognosis of patients was compared at 30, 90, 180, and 360 days after discharge. A multicenter, randomized, parallel-controlled clinical trial was conducted in a department of respiratory and critical care medicine in Central China. All patients met the inclusion criteria for AECOPD, and the patients were randomly assigned to the antibiotic group or the nonantibiotic group at a 1:1 ratio. Patients in the antibiotic group were given moxifloxacin 400 mg/day intravenously for 7 days. Patients in the nonantibiotic group were intravenously injected with the same amount of normal saline as the amount of moxifloxacin given to those in the antibiotic group for 7 days.ResultsThere were 406 patients in the antibiotic group and 410 patients in the nonantibiotic group. During the short-term and long-term follow-ups, the acute exacerbation frequency, intensive care unit (ICU) treatment rate, mortality, and mMRC and CAT scores were not significantly different between the two groups (p > 0.05). At the 180- and 360-day follow-ups, the forced expiratory volume in 1 s (FEV1%) and peak expiratory flow (PEF) were not significantly different between the two groups (p > 0.05). The 30-day readmission rate was significantly lower in the antibiotic group than in the nonantibiotic group (p < 0.05). The time from discharge to the first acute exacerbation was not significantly different between the two groups (p > 0.05). The length of the first hospital stay after discharge was significantly lower in the antibiotic group (5.84 days) than in the nonantibiotic group (6.75 days) (p < 0.05). At the 30-day follow-up, the acute exacerbation frequency, age, C-reactive protein (CRP) level, and sputum viscosity were significantly greater in the nonantibiotic group than in the antibiotic group (p < 0.05). In addition, according to the receiver operating characteristic (ROC) analysis, the frequency of acute exacerbations at the 30-day follow-up was significantly greater in COPD patients aged >62.5 years, with a CRP level >12.56 mg/L or with a sputum viscosity >III, in the nonantibiotic group than in those in the antibiotic group, suggesting that the short-term prognosis was poor.ConclusionPatients who are >62.5 years of age, have a CRP concentration >12.56 mg/L, or have a sputum viscosity >III without obvious signs of infection should be treated with antibiotics to improve their short-term prognosis.Clinical Trial Registration:(https://www.chictr.org.cn), (ChiCTR1800018921)

BackgroundTuberculosis (TB) is recognized as a significant global public health concern. Still, there remains a dearth of comprehensive evaluation regarding the specific indicators and their influencing factors of delay for adolescents and young adults.MethodsAll notified pulmonary TB (PTB) patients in Jiaxing City were collected between 2005 and 2022 from China’s TB Information Management System. Logistic regression models were conducted to ascertain the factors that influenced patient and health system delays for PTB cases, respectively. Furthermore, the impact of the COVID-19 pandemic on local delays has been explored.ResultsFrom January 1, 2005 to December 31, 2022, a total of 5,282 PTB cases were notified in Jiaxing City, including 1,678 adolescents and 3,604 young adults. For patient delay, female (AOR: 1.18, 95%CI: 1.05–1.32), PTB complicated with extra-pulmonary TB (AOR: 1.70, 95% CI: 1.28–2.26), passive case finding (AOR: 1.46, 95% CI: 1.07–1.98) and retreatment (AOR: 1.52, 95% CI: 1.11–2.09) showed a higher risk of delay. For health system delay, minorities (AOR: 0.69, 95% CI: 0.53–0.90) and non-students (AOR: 0.83, 95% CI: 0.71–0.98) experienced a lower delay. Referral (AOR: 1.46, 95% CI: 1.29–1.65) had a higher health system delay compared with clinical consultation. Furthermore, county hospitals (AOR: 1.47, 95% CI: 1.32–1.65) and etiological positive results (AOR: 1.46, 95% CI: 1.30–1.63) were associated with comparatively high odds of patient delay. Contrarily, county hospitals (AOR: 0.88, 95% CI: 0.78–1.00) and etiological positive results (AOR: 0.67, 95% CI: 0.59–0.74) experienced a lower health system delay. Besides, the median of patient delay, health system delay, and total delay during the COVID-19 pandemic were significantly lower than that before.ConclusionIn general, there has been a noteworthy decline in the notification rate of PTB among adolescents and young adults in Jiaxing City while the declining trend was not obvious in patient delay, health system delay, and total delay, respectively. It also found factors such as gender, case-finding method, and the hospital level might influence the times of seeking health care and diagnosis in health agencies. These findings will provide valuable insights for refining preventive and treatment strategies for TB among adolescents and young adults.

The development of the β-solidifying γ-TiAl alloys with good oxidation resistance and thermal deformation ability has always been crucial for the practical application. However, increasing the content of the antioxidant elements, such as Nb, Al, etc., tends to be detrimental to the deformability of the alloys. In this work, a novel Nb, Mn containing β-solidifying TiAl alloy with the nominal composition of Ti-43Al-1.5Mn-3Nb-0.2C-0.2Si-0.1B (at. %) (named as NbMn-TiAl) is invented, which goes through the single β phase as well as the α phase during solidification, resulting in the final as-cast microstructure of nearly full lamellar structure (NFL). Subsequently, the isothermal compression tests were performed within a temperature range of 1100 °C–1300 °C and a strain rate range of 0.001 s−1-10 s−1, the hot processing maps and constitutive equation were established. Moreover, the deformation mechanisms were clarified, including the bending/kinking of the α2/γ lamellar colonies, the dynamic recrystallization (DRX) of γ phase and α phase at different temperatures. Rolled bars with a diameter of 12 mm were then directly fabricated from the ingot by conventional hot rolling process. The as-rolled bars exhibited excellent oxidation resistance and mechanical properties that outperform many available TiAl alloys manufactured using various methods.

Open-pit mining is a cornerstone of industrial raw material extraction, yet it is fraught with safety concerns due to rough operating conditions. The advent of Industry 4.0 has introduced advanced technologies such as AI, the IoT, and autonomous systems, setting the stage for a paradigm shift towards unmanned mining operations. With this study, we addressed the urgent need for safe and efficient production based on intelligent unmanned mining systems in open-pit mines. A collaborative production planning model was developed for an intelligent unmanned system comprising multiple excavators and mining trucks. The model is formulated to optimize multiple objectives, such as total output, equipment idle time, and transportation cost. A multi-objective optimization approach based on the genetic algorithm was employed to solve the model, ensuring a balance among conflicting objectives and identifying the best possible solutions. The computational experiments revealed that the collaborative production planning method significantly reduces equipment idle time and enhances output. Moreover, with the proposed method, by optimizing the configuration to include 6 unmanned excavators, 50 unmanned mining trucks, and 4 unloading points, a 92% reduction in excavator idle time and a 44% increase in total output were achieved. These results show the model’s potential to transform open-pit mining operations by using intelligent planning.

Abstract Quantum teleportation constitutes a fundamental tool for various applications in quantum communication and computation. However, state-of-the-art continuous-variable quantum teleportation is restricted to moderate fidelities and short-distance configurations. This is due to unavoidable experimental imperfections resulting in thermal decoherence during the teleportation process. Here we present a heralded quantum teleporter able to overcome these limitations through noiseless linear amplification. As a result, we report a high fidelity of 92% for teleporting coherent states using a modest level of quantum entanglement. Our teleporter in principle allows nearly complete removal of loss induced onto the input states being transmitted through imperfect quantum channels. We further demonstrate the purification of a displaced thermal state, impossible via conventional deterministic amplification or teleportation approaches. The combination of high-fidelity coherent state teleportation alongside the purification of thermalized input states permits the transmission of quantum states over significantly long distances. These results are of both practical and fundamental significance; overcoming long-standing hurdles en route to highly-efficient continuous-variable quantum teleportation, while also shining new light on applying teleportation to purify quantum systems from thermal noise.

Abstract Ammonia serves as an irreplaceable raw material for nitrogen fertilizers, which is essential for global food production. In addition, it has been recently endowed with a new function as a carrier of renewable energy, demonstrating significant research prospects. However, the highly developed ammonia industry results in abundant nitrogenous wastes in nature, thus causing severe nitrogen pollution and disrupting the global nitrogen cycle. The environmentally friendly electrocatalytic technologies for upcycling nitrogenous wastes to green ammonia represent a highly valuable transformation strategy. In this review, we present three effective pathways for the electrocatalytic reduction of nitrogenous wastes to green ammonia, including nitrate reduction reaction (NO3RR), nitrite reduction reaction (NO2RR), and nitric oxide reduction reaction (NORR). Furthermore, achievements and challenges associated with electrocatalysts for green ammonia synthesis are discussed in terms of noble metal-based electrocatalysts, non-noble metal-based electrocatalysts, and metal-free electrocatalysts. Moreover, this review provides a systematic perspective on reaction mechanisms, catalyst design, and future developments, offering new insights and prospects for the value-upgrading cycle of nitrogenous substances. By exploring the potential of green ammonia synthesis, we aim to contribute to the development of sustainable and environmentally friendly ammonia production.

Dielectric ceramics are promising in large-scale commercial millimeter-wave communication technology, such as 5G and the upcoming 6G, thanks to their excellent frequency selection characteristics and environmental stability. In this work, various contents of SbO bonds were introduced into the MgTa2O6 lattice using the solid-phase reaction method to investigate the effects on the lattice and microwave dielectric properties. XRD confirms that Sb ions successfully occupy Ta sites in the lattice and cause lattice shrinkage and crystallinity deterioration, which leads to a slight decrease in the quality factor. Furthermore, DFT calculations reveal that the doping leads to electron-biased aggregation toward O atoms, causing higher SbO ionicity, but also attenuates the degree of ionization of Ta and Mg ions, which makes the dielectric constant of the doped samples vary non-monotonically with gradient doping. Satisfactorily, Sb doping substantially enhanced the thermal stability of the ceramics, with TCF values reduced from 36 × 10−6 °C-1 to 15 × 10−6 °C-1.

There is a need to develop and adopt novel, more resilient, or “climate-smart” cropping strategies on the Canadian prairies, which are crucial for sustainable agroecosystem management. To examine how crop rotation influences soil organic matter and aggregate stability (AS) dynamics, six crop rotations: (i) conventional (control), (ii) pulse/oilseed intensified, (iii) diversified, (iv) market-driven, (v) high-risk and high-reward, and (vi) soil health-enhanced were established in 2018 at three field sites: Lethbridge, Alberta and Swift Current and Scott, Saskatchewan under no-till management. After 4-year, soil organic carbon (SOC), total nitrogen (TN), particulate organic matter carbon (POM-C) and nitrogen (POM-N), or mineral-associated organic matter C (MAOM-C) and N (MAOM-N) concentrations were not significantly affected by crop rotation in the 0–7.5 cm soil depth. However, crop rotation significantly altered AS at two of three sites, with both soil health-enhanced and high-risk and high-reward rotations having the highest AS at Lethbridge and Swift Current. Across all three sites, strong positive correlations were found among SOC, TN, MAOM, and AS. Moreover, MAOM-C and MAOM-N showed stronger relationships with AS than POM, perhaps suggesting a positive feedback loop on the stability of SOC and aggregation. Overall, the inclusion of pulses in rotations showed the potential to sustain soil quality, likely by offsetting low residue quantity with better residue quality and diversity, thereby supporting SOC accrual and AS similar to or greater than conventional cereal- or oilseed-dominated rotations.

BackgroundHigh-quality medication compliance is critical for the cure of pulmonary tuberculosis (PTB); however, the implementation of directly observed treatment (DOT) under direct interview still faces huge difficulties. Assessment of the effect of digital tool during community management has not been performed in eastern China.MethodsAll drug-sensitive PTB cases notified in Yiwu city from June to December 2020 were divided into the routine group and digital tool group based on patients’ willingness. The variables influencing the on-time completion level of home visits, medication adherence and treatment outcomes were estimated.ResultsA total of 599 eligible patients were enrolled, with 268 participating in the routine group and 331 using a digital tool. Most participants were men (n = 357, 59.6%), and nearly all were new cases (n = 563, 94.0%). Participants’ mean age was 44.22 ± 20.32 years. There were significant differences in age, diagnostic type, and source of patients between the two groups. During the study period, the digital tool group had a higher on-time completion rate of home visits (91.5% vs. 82.5%) and medication adherence rate (94.3% vs. 89.6%) than the routine group, whereas there was no significant difference in the treatment success rate between the two groups (91.2% vs. 86.8%). Multivariate logistic regression analysis demonstrated that the digital tool group showed a more positive function in the on-time completion status of home visits, with an adjusted odds ratio of 0.41 (95% confidence interval: 0.25–0.70).ConclusionDigital tools can be employed to improve the on-time completion rate of home visits in Yiwu city. Further large-scale studies that use digital tools for community management are warranted.

Summary: Dynamic chromosome remodeling and nuclear compartmentalization take place during mammalian meiotic prophase I. We report here that the crucial roles of male pachynema-specific protein (MAPS) in pachynema progression might be mediated by its liquid-liquid phase separation in vitro and in cellulo. MAPS forms distinguishable liquid phases, and deletion or mutations of its N-terminal amino acids (aa) 2−9 disrupt its secondary structure and charge properties, impeding phase separation. Maps−/− pachytene spermatocytes exhibit defects in nucleus compartmentalization, including defects in forming sex bodies, altered nucleosome composition, and disordered chromatin accessibility. MapsΔ2–9/Δ2–9 male mice expressing MAPS protein lacking aa 2–9 phenocopy Maps−/− mice. Moreover, a frameshift mutation in C3orf62, the human counterpart of Maps, is correlated with nonobstructive azoospermia in a patient exhibiting pachynema arrest in spermatocyte development. Hence, the phase separation property of MAPS seems essential for pachynema progression in mouse and human spermatocytes.

Shanghai Pudong International Airport (PDIA), with its east side built along the coast with weak geological conditions, is prone to uneven foundation settlement due to the consolidation and compression of soil and erosion of coastal tides, affecting the safe operation of the airport. Therefore, it is crucial to conduct dynamic subsidence monitoring within the airport, especially in the runway area. 29 scenes of ascending track Sentinel-1A radar images from August 2016 to June 2018 are selected to perform surface deformation inversion based on PS-InSAR and improved SBAS-InSAR for PDIA and its around coastal area. Through cross-validation, the reliability of the time-series InSAR technique for dynamic monitoring of surface deformation of coastal zone infrastructures is confirmed. The results show severely uneven settlement. By combining the monitoring results with the local geological and hydrological dataset, the driving factors of differential deformation of the infrastructures are analyzed, including stratigraphic geological conditions, ground loadings, foundation treatment methods, water erosion, and groundwater level changes. Finally, the time-series deformation characteristics and the causes of PDIA's runway are emphasized based on the PS deformation results. This case provides a reference for the safety management of critical infrastructure in coastal areas using advanced InSAR technique.

Abstract Background and objectives Lumbar ligamentum flavum cyst is a rare spinal condition that can cause significant morbidity and neurological deficits. Traditional surgical treatment involves open surgery, which can be associated with prolonged recovery time and significant morbidity. In recent years, endoscopic treatment of lumbar ligamentum flavum cyst has emerged as a minimally invasive and effective alternative to open surgery, but only a few cases have been reported in the literature. This paper describes our experience with endoscopic resection of an L4/5 ligamentum flavum cyst through an interlaminar approach and reviews the literature on the treatment of lumbar ligamentum flavum cyst. Methods An 87-year-old man presented with lameness in the left leg, and magnetic resonance imaging (MRI) showed nerve compression by a ligamentum flavum cyst at the L4/5 intervertebral plane. The patient underwent endoscopic resection of the ligamentum flavum cyst through a left interlaminar approach with the facet joint preserved. The present study was approved by the Ethics Committee of our hospital. The datasets used and/or analyzed during the current study are available from the corresponding author upon reasonable request. Text regarding patient consent is not applicable for this case. Results Postoperative clinical results improved significantly, and postoperative MRI showed complete cyst resection. Conclusion Total endoscopic resection via an interlaminar approach provides a new minimally invasive approach for the surgical treatment of lumbar ligamentum flavum cyst, which can be used as a reference by clinicians.

Abstract Background After centuries of heavy reliance on fossil fuel energy, the world suffers from an energy crisis and global warming, calling for carbon emission reduction and a transition to clean energy. Microalgae have attracted much attention as a potential feedstock for biofuel production due to their high triacylglycerol content and CO2 sequestration ability. Many diacylglycerol acyltransferases (DGAT) species have been characterized, which catalyze the final committed step in triacylglycerol biosynthesis. However, the detailed structure–function features of DGATs and the role of the interactions among DGAT proteins in lipid metabolism remained largely unknown. Results In this study, the three characterized DGATs of Auxenochlorella protothecoides 2341 showed distinct structural and functional conservation. Functional complementation analyses showed that ApDGAT1 had higher activity than ApDGAT2b in yeast and model microalgae, and ApDGAT2a had no activity in yeast. The N-terminus was not essential to the catalysis function of ApDGAT1 but was crucial to ApDGAT2b as its enzyme activity was sensitive to any N-terminus modifications. Similarly, when acyl-CoA binding proteins (ACBPs) were fused to the N-terminus of ApDGAT1 and ApDGAT2b, zero and significant activity changes were observed, respectively. Interestingly, the ApACBP3 + ApDGAT1 variant contributed to higher oil accumulation than the original DGAT1, and ApACBP1 + ApDGAT1 fusion boosted oleic acid content in yeast. Overexpression of the three DGATs and the variation of ApACBP3 + ApDGAT1 increased the content of C18:1 of Chlamydomonas reinhardtii CC-5235. Significantly, ApDGAT1 interacted with itself, ApDGAT2b, and ApACBP1, which indicated that these three lipid metabolic proteins might have been a part of a dynamic protein interactome that facilitated the enrichment of oleic acid. Conclusions This study provided new insights into the functional and structural characteristics of DGATs and elucidated the importance of these physical interactions in potential lipid channeling.

Li(1+x)2MgTi3O8 (0.0 ≤ x ≤ 0.10) ceramics with Li non-stoichiometric ratios were prepared by the solid-state reaction method to inhibit the volatilization of Li. The effects of the Li non-stoichiometric ratios on the sintering behavior, crystal structure, microscopic morphology, Raman vibrations, electron density, and dielectric properties of Li(1+x)2MgTi3O8 ceramics were systematically investigated. The Li(1+0.06)2MgTi3O8 ceramics demonstrate the best dielectric properties with εr = 26.33, Q × f = 69 435 GHz (@6.87 GHz, 54% improvement), τf = 2.95 × 10−6 °C−1. For the non-intrinsic factors, the high relative density (97.15%) and larger grain size (16.78 μm) allow the dielectric properties to be improved. As for the intrinsic factors, a reasonable excess of Li improves the bond ionicity of the Mg—O bond, the lattice energy of the Ti—O bond, and the electron cloud density, thus optimizing the dielectric properties. Raman spectroscopy leads to the same result from the point of view of lattice vibrations. At the same time, the distortion of the polyhedra is also improved, so that τf also approaches 0. The improved Li(1+0.06)2MgTi3O8 has potential applications in microwave communication technology.

TanDEM-X bistatic interferometric system successfully generated a high-precision, high-resolution global digital elevation model (DEM). However, in forested areas, two core problems make it difficult to obtain sub-canopy topography: (1) the penetrability of short-wave signals is limited, and the DEM obtained in dense forest areas contains a significant forest signal, that is, the scattering phase center (SPC) height; and (2) the single-baseline and single-polarization TanDEM-X interferometric synthetic aperture radar (InSAR) data cannot provide sufficient observations to make the existing physical model reversible for estimating the real surface phase, whereas the introduction of optical data makes it difficult to ensure data synchronization and availability of cloud-free data. To overcome these problems in accurately estimating sub-canopy topography from TanDEM-X InSAR data, this study proposes a practical method of sub-canopy topography estimation based on the following innovations: (1) An orthogonal polynomial model was established using TanDEM-X interferometric coherence and slope to estimate the SPC height. Interferometric coherence records forest height and dielectric property information from an InSAR perspective and has spatiotemporal consistency with the InSAR-derived DEM. (2) Introduce Ice, Cloud, and Land Elevation Satellite-2 (ICESat-2) data to provide more observational information and automatically screen ICESat-2 control points with similar forest and slope conditions in the local area to suppress forest spatial heterogeneity. (3) A weighted least squares criterion was used to solve this model to estimate the SPC height. The results were validated at four test sites using high-precision airborne light detection and ranging (LiDAR) data as a reference. Compared to the InSAR-derived DEM, the accuracy of the sub-canopy topography was improved by nearly 60%, on average. Furthermore, we investigated the necessity of local modeling, confirming the potential of the proposed method for estimating sub-canopy topography by relying only on TanDEM-X and ICESat-2 data.

The North Huicheng Basin strike-slip fault system is on the northeastern frontier of the Tibetan Plateau and separates the West and East Qinling differential orogeny. However, the deformation mechanism of this strike-slip fault system and its exact tectonic significance are unclear. Here, we carried out systematic field structural analysis, physical analog modeling, and multiproxy geochronological dating to address these issues. The field structural analysis indicates that the North Huicheng Basin strike-slip fault system was induced from the plate-like movement of the West and East Qinling Orogens, which underwent multiple left-lateral strike-slip faulting and controlled salient and recessed structures. The scaled physical analog experiment results confirm this hypothesis and reveal the primary spatial-temporal deformational kinematic process. Combined with published works, multiproxy geochronological dating (zircon U‒Pb age of 213 Ma, biotite 40Ar/39Ar age of 203 Ma, and apatite fission-track age of 56 Ma) outlines the main thermal history of the hanging wall. Based on the above facts, the integrated research suggests that multistage strike-slip faulting played a significant role in the main tectonic events, that is, late Triassic magmatic emplacement, Jurassic/Cretaceous local pull-apart, and Cenozoic rapid exhumation driven by Tibetan Plateau growth.

BackgroundMachine learning (ML) models provide more choices to patients with diabetes mellitus (DM) to more properly manage blood glucose (BG) levels. However, because of numerous types of ML algorithms, choosing an appropriate model is vitally important. ObjectiveIn a systematic review and network meta-analysis, this study aimed to comprehensively assess the performance of ML models in predicting BG levels. In addition, we assessed ML models used to detect and predict adverse BG (hypoglycemia) events by calculating pooled estimates of sensitivity and specificity. MethodsPubMed, Embase, Web of Science, and Institute of Electrical and Electronics Engineers Explore databases were systematically searched for studies on predicting BG levels and predicting or detecting adverse BG events using ML models, from inception to November 2022. Studies that assessed the performance of different ML models in predicting or detecting BG levels or adverse BG events of patients with DM were included. Studies with no derivation or performance metrics of ML models were excluded. The Quality Assessment of Diagnostic Accuracy Studies tool was applied to assess the quality of included studies. Primary outcomes were the relative ranking of ML models for predicting BG levels in different prediction horizons (PHs) and pooled estimates of the sensitivity and specificity of ML models in detecting or predicting adverse BG events. ResultsIn total, 46 eligible studies were included for meta-analysis. Regarding ML models for predicting BG levels, the means of the absolute root mean square error (RMSE) in a PH of 15, 30, 45, and 60 minutes were 18.88 (SD 19.71), 21.40 (SD 12.56), 21.27 (SD 5.17), and 30.01 (SD 7.23) mg/dL, respectively. The neural network model (NNM) showed the highest relative performance in different PHs. Furthermore, the pooled estimates of the positive likelihood ratio and the negative likelihood ratio of ML models were 8.3 (95% CI 5.7-12.0) and 0.31 (95% CI 0.22-0.44), respectively, for predicting hypoglycemia and 2.4 (95% CI 1.6-3.7) and 0.37 (95% CI 0.29-0.46), respectively, for detecting hypoglycemia. ConclusionsStatistically significant high heterogeneity was detected in all subgroups, with different sources of heterogeneity. For predicting precise BG levels, the RMSE increases with a rise in the PH, and the NNM shows the highest relative performance among all the ML models. Meanwhile, current ML models have sufficient ability to predict adverse BG events, while their ability to detect adverse BG events needs to be enhanced. Trial RegistrationPROSPERO CRD42022375250; https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=375250

BackgroundTuberculous pleurisy (TP) presents a serious allergic reaction in the pleura caused by Mycobacterium tuberculosis; however, few studies have described its spatial epidemiological characteristics in eastern China. ObjectiveThis study aimed to determine the epidemiological distribution of TP and predict its further development in Zhejiang Province. MethodsData on all notified cases of TP in Zhejiang Province, China, from 2017 to 2021 were collected from the existing tuberculosis information management system. Analyses, including spatial autocorrelation and spatial-temporal scan analysis, were performed to identify hot spots and clusters, respectively. The prediction of TP prevalence was performed using the seasonal autoregressive integrated moving average (SARIMA), Holt-Winters exponential smoothing, and Prophet models using R (The R Foundation) and Python (Python Software Foundation). ResultsThe average notification rate of TP in Zhejiang Province was 7.06 cases per 100,000 population, peaking in the summer. The male-to-female ratio was 2.18:1. In terms of geographical distribution, clusters of cases were observed in the western part of Zhejiang Province, including parts of Hangzhou, Quzhou, Jinhua, Lishui, Wenzhou, and Taizhou city. Spatial-temporal analysis identified 1 most likely cluster and 4 secondary clusters. The Holt-Winters model outperformed the SARIMA and Prophet models in predicting the trend in TP prevalence. ConclusionsThe western region of Zhejiang Province had the highest risk of TP. Comprehensive interventions, such as chest x-ray screening and symptom screening, should be reinforced to improve early identification. Additionally, a more systematic assessment of the prevalence trend of TP should include more predictors.

BackgroundEnterocutaneous fistula is one of the most challenging problems facing surgeons. In severe cases, a large amount of fluid loss can lead to problems such as water and electrolyte acid-base imbalance, malnutrition, infection, and organ dysfunction. Here we reported a case of platelet-rich plasma combined with lyophilizing thrombin powder for the treatment of complicated enterocutaneous fistula.Case presentationA 48-year-old male, more than 2 years after the operation of abdominal trauma, the leakage of the fistula in the right upper abdominal wall was accompanied by fever for 3 days. The Contrast Fistulography and upper abdomen CT accurately depicted the entry of the meglumine diatrizoate into the small intestine through the small fistula. The patient had a large abdominal wall defect and severe intestinal adhesions. Reoperation may lead to more serious ECF. Therefore, we decided to seal the fistulas with PRP combined with lyophilizing thrombin powder.ConclusionsThe findings in this case report suggest that the combination of PRP and lyophilized thrombin powder holds promise as a viable approach for managing ECF in patients with chronic abdominal wall fistulas, as it appears to facilitate fistula closure, reduce healing time, and improve patient outcomes

Abiotic stress such as high temperature at flowering is one of many conditions reducing yield of corn (Zea mays L.). Mixing corn cultivars with diverse functional traits increases within-crop diversity and provides a potential means of mitigating yield losses under stress conditions. We conducted a three-year field study to investigate the effects of cultivar mixtures on kernel setting rate, pollen sources, and yield. This study consisted of six treatments, including two high temperature-tolerant (HTT) monocrops of WK702 and DH701, two high temperature-sensitive (HTS) monocrops of DH605 and DH662, and two HTT–HTS mixtures of WK702-DH605 and DH701-DH662. The anthesis–silking interval (ASI) was 0.9–1.6 days shorter in mixtures than in monocrops. Kernel setting rate was increased in mixtures (86.4%–88.7%) compared with those in monocrops (74.7%–84.1%) as a result of synchrony and complementarity of pollination. Grain yields of the HTT–HTS mixtures increased by 13.3%–18.7%, equivalent to 1169 to 1605 kg ha−1, in comparison with HTS corn monocrops. The results of SSR markers showed that cross-fertilization percentage in corn cultivar mixtures ranged from 29.3% to 47.8%, partially explaining yield improvement. Land equivalent ratio (LER) was 1.12 for corn mixtures and the partial land equivalent ratio (e.g., > 0.5) showed the complementary benefits in corn mixtures. The results indicated that mixing corn cultivars with diverse flowering and drought-tolerance traits increased yields via pollination synchrony.

Background The epidemic of type 2 diabetes mellitus (T2DM) poses a great challenge to pulmonary tuberculosis (PTB) control. However, the incidence and prevalence of PTB among T2DM patients has not been fully determined. This meta-analysis aimed to provide the estimation on the global incidence and prevalence of PTB among T2DM patients (T2DM-PTB).Methods Online databases including Web of Science, PubMed, China National Knowledge Infrastructure and Cochrane Library were searched for all relevant studies that reported the incidence or prevalence of T2DM-PTB through 31 January 2022. Pooled incidence and prevalence of T2DM-PTB with 95% confidence interval (CI) was estimated by the random-effect model. All statistical analyses were performed using R software.Results A total of 24 studies (14 cohort studies, 10 cross-sectional studies) were included. The pooled incidence and prevalence of T2DM-PTB were 129.89 per 100,000 person-years (95% confidence interval (CI): 97.55–172.95) and 511.19 per 100,000 (95% CI: 375.94–695.09), respectively. Subgroup analyses identified that the incidence of T2DM-PTB was significantly higher in Asia (187.20 per 100,000 person-years, 95% CI: 147.76–237.17), in countries with a high TB burden (172.04 per 100,000 person-years, 95% CI: 122.98–240.68) and in studies whose data collection ended before 2011 (219.81 per 100,000 person-years, 95% CI: 176.15–274.28), but lower in studies using International Classification of Diseases-10 codes (73.75 per 100,000 person-years, 95% CI: 40.92–132.91). The prevalence of T2DM-PTB was significantly higher in countries with a high TB burden (692.15 per 100,000, 95% CI: 468.75–1022.04), but lower in Europe (105.01 per 100,000, 95% CI: 72.55–151.98).Conclusions This systematic review and meta-analysis suggests high global incidence and prevalence of PTB among T2DM patients, underlining the necessity of more preventive interventions among T2DM patients especially in countries with a high TB-burden. Key messagesA total of 24 studies (14 cohort studies, 10 cross-sectional studies) containing 2,569,451 T2DM patients were included in this meta-analysis.The pooled incidence and prevalence of T2DM-PTB are 129.89 per 100,000 person-years (95% CI: 97.55–172.95) and 511.19 per 100,000 (95% CI: 375.94–695.09) respectively.The incidence of T2DM-PTB was significantly higher in Asia, in countries with a high TB burden and in studies whose data collection ended before 2011, but lower in studies using International Classification of Diseases-10 codes.The prevalence of T2DM-PTB was significantly higher in countries with a high TB-burden, but lower in Europe.

With the widespread application of wireless communication technology and continuous improvements to Internet of Things (IoT) technology, fog computing architecture composed of edge, fog, and cloud layers have become a research hotspot. This architecture uses Fog Nodes (FNs) close to users to implement certain cloud functions while compensating for cloud disadvantages. However, because of the limited computing and storage capabilities of a single FN, it is necessary to offload tasks to multiple cooperating FNs for task completion. To effectively and quickly realize task offloading, we use network calculus theory to establish an overall performance model for task offloading in a fog computing environment and propose a Globally Optimal Multi-objective Optimization algorithm for Task Offloading (GOMOTO) based on the performance model. The results show that the proposed model and algorithm can effectively reduce the total delay and total energy consumption of the system and improve the network Quality of Service (QoS).

Abstract Osteosarcoma (OS), the most common primary malignancy of the bone, has a poor prognosis due to its high mortality rate and high potential for metastasis. Thus, it is urgently necessary to explore functional molecular targets of therapeutic strategies for osteosarcoma. Here, we reported that TIPE1 expression was decreased in osteosarcoma tissues compared to normal and adjacent nontumor tissues, and its expression was negatively related to tumor stage and tumor size. Functional assays showed that TIPE1 inhibited osteosarcoma carcinogenesis and metastatic potential both in vivo and in vitro. Furthermore, we investigated that the STAT3 signaling pathway was significantly downregulated after TIPE1 overexpression. Mechanistically, TIPE1 bind to the catalytic domain of PRMT1, which deposits an asymmetric dimethylarginine (ADMA) mark on histone/non-histone proteins, and thus inhibited PRMT1 mediated STAT3 methylation at arginine (R) residue 688. This abolished modification decreased STAT3 transactivation and expression, by which subsequently suppressed osteosarcoma malignancy. Taken together, these data showed that TIPE1 inhibits the malignant transformation of osteosarcoma through PRMT1-mediated STAT3 arginine methylation and ultimately decreases the development and metastasis of osteosarcoma. TIPE1 might be a potential molecular therapeutic target and an early biomarker for osteosarcoma diagnosis.

BackgroundTuberculosis (TB) remains a major public health challenge. However, indicators of delays in assessing effective TB prevention and control and its influencing factors have not been investigated in the eastern coastal county of China.MethodsAll notified pulmonary tuberculosis (PTB) cases in the Fenghua District, China were collected between 2010 and 2021 from the available TB information management system. Comparison of delays involving patient, health system, and total delays among local and migrant cases. Additionally, in correlation with available Basic Public Health Service Project system, we performed univariate and multivariate logistic regression analyses identified the influencing factors associated with patient and total delays in patients aged >60 years.ResultsIn total, 3,442 PTB cases were notified, including 1,725 local and 1,717 migrant patients, with a male-to-female ratio of 2.13:1. Median patient and total delays of local TB patients were longer than those for migrant patients; the median health system delay did not show any significant difference. For patient delay among the older adult, female (cOR: 1.93, 95% CI: 1.07–3.48), educational level of elementary school and middle school (cOR: 0.23, 95% CI: 0.06–0.84) had a statistical difference from univariable analysis; however, patients without diabetes showed a higher delay for multiple-factor analysis (aOR: 2.12, 95% CI: 1.02–4.41). Furthermore, only the education level of elementary school and middle school presented a low total delay for both univariate (cOR: 0.22, 95% CI: 0.06–0.82) and multivariate analysis (aOR: 0.21, 95% CI: 0.05–0.83) in the older patients.ConclusionThe delay of TB cases among migrants was lower than the local population in the Fenghua District, which may be related to the “healthy migrant effect”. It highlights that women, illiterate people, and people without diabetes are key groups for reducing delays among older adults. Health awareness should focus on these target populations, providing accessible health services, and reducing the time from symptom onset to diagnosis.

Abstract Background The deficiency of serine/threonine protein kinase 11 (STK11), one of the most common tumor suppressor genes in non‐small‐cell lung cancer, is a crucial player in tumor immune microenvironment regulation. This study attempted to unveil how mutated STK11 impact the differentiation of macrophages in lung adenocarcinoma (LUAD). Methods STK11 and CD1E expression levels in different cell models were assessed by quantitative reverse transcription polymerase chain reaction. Western blot was utilized to detect the protein expression levels of STK11, CD1E, apoptosis markers, and AMPK signaling pathway markers after transfection treatment. Cell viability and macrophage differentiation were detected by CCK‐8 and flow cytometry. Immunohistochemistry and immunofluorescence were employed to detect the expression of related genes and macrophage markers, respectively. Results This study found that STK11 mutations promoted the proliferation of LUAD cells and inhibited the differentiation of M1 macrophages, apoptosis, and the AMPK signaling pathway. Mutated STK11 led to CD1E downregulation, which curbed the differentiation of M1 macrophages and hence promoted LUAD progression. It was further validated by the in vivo experimental results that STK11 mutation significantly decreased the immune infiltration of M1 macrophages and promoted LUAD progression. Conclusion It was revealed that STK11 mutation affected CD1E expression to regulate macrophage differentiation in LUAD and then promote tumor progression. In this way, CD1E could be a potential biological target for the therapeutic interventions of STK11‐mutant LUAD patients. These findings also threw new light on a new therapeutic strategy for STK11‐mutant tumor patients that assisted the macrophage polarization pathway.

BackgroundMyopia is an increasingly serious public concern, particularly among primary school students. The prevalence of myopia and its influencing factors in primary school pupils in Eastern China during the COVID-19 pandemic had not been explored.MethodsA randomly clustered sampling method was performed, and selected pupils from grade 1 to grade 3 in 15 primary schools in the Fenghua District of Zhejiang Province were included and given myopia screening and uniform questionnaire survey 1 year later.ResultsA total of 4,213 students completed the myopia screening and questionnaire survey. Myopia was diagnosed in 1,356 pupils, with a myopia incidence of 32.19%. The spherical equivalent (SE) refraction of the included pupils decreased on average by 0.50 ± 2.15 D 1 year later. The myopia rate was positively correlated with the increase of grade, in which the myopia rate among grade 3 students was the highest at 39.69%. The myopia rate among female students was higher than that among male students. Students residing in urban areas had a higher myopia rate than in rural areas. Maintaining an near work distance ≥33 cm was a significant protective factor (OR = 0.84, 95% CI: 0.74–0.96). Students with two myopic parents had a higher risk of myopia (OR = 1.61, 95% CI: 1.34–1.92).ConclusionDuring the COVID-19 pandemic, the myopia rate among early primary school students in Eastern China was high. More attention and implementation of interventions from health and education departments, such as training the development of good eye behavior, should be considered to strengthen the intervention of myopia in primary school students.

This study developed an objective identification algorithm for the Southwest Vortex (SWV), the dominant rainstorm system prevalent in Southwest China. Based on the TempestExt package, the newly developed SWV identification algorithm employed a 12 h minimum duration threshold, utilizing the high-resolution ERA5 dataset with 1 h intervals. The results reveal that the algorithm precisely identifies the SWV records documented in the SWV Yearbooks, achieving an optimal balance of high probability of detection and low false alarm rate. In addition, the algorithm can detect the SWVs in advance, offering a significant enhancement to SWV monitoring. Notably, the algorithm-detected SWVs exhibit a strong correlation with rainstorms, with a correlation coefficient of 0.70. From an on-site precipitation perspective, the algorithm-detected SWVs account for 87.6% of the observed rainstorm days. Collectively, this study introduces an updated tool for the SWV identification and underscores the algorithm’s promising potential in improving rainstorm forecasts in Southwest China.

The excavation of a super-large foundation pit is a greatly risky project in coastal water-rich silt strata, and it is of great significance to establish a numerical model to analyze and predict the stability of the foundation pit retaining its structure for safe construction. Based on a geological investigation report and key node monitoring data, the model parameters have been modified. Subsequently, the random field theory and numerical analysis were employed to proceed with deterministic analysis and uncertainty analysis, respectively. Using the uniform distribution method, Gaussian distribution method and the covariance matrix method to generate a random field model, finite difference software was applied to analyze the impact of spatial variability of cohesion and the internal friction angle on structural deformation. The study shows that the overall distribution of axial force is small on both sides and large in the center, and the axial force is larger near the shaped region. Due to the principle of “lever”, there is a tendency for the horizontal displacement of surrounding piles to partially rebound from the pit when the bearing platform pit is excavated. The spatial variability of the internal friction angle and cohesion has an important influence on the numerical value of the enclosure structure and surface deformation, and the variation pattern is basically unchanged.

Chemotherapy is extensively used to treat cancers and is often associated with ovarian damage and leads to premature ovarian insufficiency and infertility, while the role of mitochondria during ovarian damage with chemotherapy remains unknown. This study used a mouse model with oocyte-specific deletion of mitochondrial stress response gene Caseinolytic peptidase P (Clpp) to investigate mitochondrial homeostasis in oocytes from mice receiving a chemotherapeutic drug cyclophosphamide (CTX). We found that oocyte-specific deletion of Clpp reduced fecundity of the mice at advanced age. The deletion led to meiotic defects with elevated abnormal spindle rate and aneuploidy rate with impaired mitochondrial function in the MII oocytes from 8-week-old mice. Upon CTX treatment at 8-week-old, the oocyte competence and folliculogenesis from the oocyte-specific Clpp knockout mice was further deteriorated with dramatic impairment of mitochondrial distribution and function including elevated ROS level, decreased mitochondrial membrane potential, respiratory chain activity and ATP production. Taken together, the results indicate that that ClpP was required for oocyte competence during maturation and early folliculogenesis, and its deficiency deteriorate cyclophosphamide-induced ovarian damage.

ObjectiveWe conducted a scientometric and visual analysis of meningioma studies in the past ten years and discussed the current status and trends of meningioma research to provide a reference basis for conducting relevant clinical practice or research.MethodA search of the topic of meningioma in the Web of Science Core Collection database was conducted for January 2012-December 2021. The scientometric tools CiteSpace (version 5.8.R3), VOS viewer (version 1.6.17), and the Bibliometrix package of R software (version 4.2.1) were used to visualize and analyze the country of publication, institution, author, keywords, and cited literature of meningioma.ResultsA total of 10,397 documents related to meningioma were collected, of which 6,714 articles were analyzed. The annual analysis shows an increase in published articles, with an annual growth rate of 8.9%. 26,696 authors from 111 countries or regions were involved in publishing relevant studies. The country with the highest number of publications was the United States (1671), and the institution with the highest number of publications was the University of California, San Francisco (242). The keyword clustering of current studies can be grouped into five groups: meningioma characteristics and basic research, surgical treatment, radiation therapy, stereotactic radiosurgery, and management of complications. Keyword trend analysis shows that meningioma classification and molecular characteristics are emerging hotspots for meningioma research in recent years.ConclusionThe scientometric and visual analysis demonstrated the research status and trends of meningioma. Over the past decade, meningioma research has focused on managing meningiomas with a predominance of surgical treatment and radiation therapy. At the same time, meningioma classification and molecular characteristics are emerging as current and possible research hotspots in the coming period.