Search

Abstract Chronic apical periodontitis is a prevalent oral disease characterized by bone loss, and its underlying mechanisms remain unclear. This study aimed to investigate the role and mechanism of the serine protease GZMA in osteoclasts during chronic apical periodontitis. To address this, we employed crRNA/Cas13d to inhibit GZMA expression and examined its impact on osteoclast behavior. Our findings revealed that GZMA plays a significant role in promoting osteoclast cell proliferation while inhibiting cell apoptosis. Additionally, the inhibition of GZMA led to a notable increase in miR-25-3p expression, which, in turn, downregulated the expression of TGF-β. Consequently, the reduction in TGF-β expression led to a decrease in PAR1 expression within the PARs pathway. These results suggest that GZMA might serve as a promising therapeutic target for the treatment of chronic apical periodontitis. Furthermore, our study highlights the potential of targeting GZMA using crRNA/Cas13d as a valuable approach for future therapeutic interventions.

Abstract Background PYL (Pyrabactin resistance 1-like) protein is a receptor of abscisic acid (ABA), which plays an important role in ABA signaling and influences plant growth and development and stress response. However, studies on PYL gene family in tea plants have not been reported. Results In this study, we identified 20 PYL genes from the reference genome of tea plant (‘Shuchazao’). Phylogeny analysis indicated that PYLs from tea and other plant species were clustered into seven groups. The promoter region of PYL genes contains a large number of cis-elements related to hormones and stresses. A large number of PYL genes responding to stress were found by analyzing the expression levels of abiotic stress and biotic stress transcriptome data. For example, CSS0047272.1 were up-regulated by drought stress, and CSS0027597.1 could respond to both anthracnose disease and geometrid feeding treatments. In addition, 10 PYL genes related to growth and development were verified by RT-qPCR and their tissue expression characteristics were revealed. Conclusions Our results provided a comprehensive characteristic of the PYL gene family in tea plants and provided an important clue for further exploring its functions in the growth and development, and resistance to stress of tea plants.

Based on ultrasound-assisted extraction, a method for determination of inorganic arsenic in various supplementary food for infants and young children was established. The samples were successively subjected to ultrasonic extraction, n-hexane purification, membrane filtration, and anion column (PRP-X 100, 10 μm, 4.1 mm×250 mm) separation. Then, 15 mmol/L diammonium hydrogen phosphate solution (pH=6.0) was used as the mobile phase. After isocratic elution, it was detected by atomic fluorescence spectrometer. The results showed that the linear relationship of arsenic forms was good in the concentration range of 5~100 ng/mL, with correlation coefficient of each component of above 0.999. The detection limit of the method was 0.010 mg/kg. The recoveries of inorganic arsenic at three spiked concentration levels ranged from 88.7% to 96.3%, and the relative standard deviation (RSD) was 1.8% to 4.9%. The method had the advantages of simple pretreatment, high extraction efficiency, fast analysis speed, high accuracy and good repeatability. Therefore, it could meet the detection requirements of different forms of inorganic arsenic in various supplementary food for infants and young children.

The seeds of Glycyrrhiza uralensis Fisch. used for cultivating are primarily sourced from wild populations. However, the types of habitats where wild G. uralensis grow are diverse. We studied the effects of salinity on the growth, antioxidant capacity, and photosynthetic physiology of two-month-old licorice seedlings from different habitats to evaluate their salt tolerance. With the increasing NaCl concentration, compared with non-salinized habitats, seedlings originating from seeds collected from salinized habitats showed milder inhibition in root biomass and root volume. Also, the crown diameter increased more significantly. Activities of superoxide dismutase, catalase, and peroxidase are higher. Correspondingly, the electrolyte leakage rate of the leaves is low. Their leaves had a higher photoprotection capacity and potential maximum photochemical efficiency of PSII. Net photosynthetic rate, transpiration rate, and stomatal conductance showed less inhibition under 4 and 6 g/kg NaCl treatment. The content of glycyrrhizic acid and glycyrrhetinic acid in their roots was significantly increased under 2 g/kg NaCl treatment and was significantly higher than that of seedlings from non-salinized habitats under the same NaCl treatment. In conclusion, seeds from salinized habitats show improved tolerance to salt stress at the seedling stage, which is attributed to their superior phenotypic adaptability, strong antioxidant, and especially high light protection ability.

Time-series Interferometric Synthetic Aperture Radar (InSAR) technology, renowned for its high-precision, wide coverage, and all-weather capabilities, has become an essential tool for Earth observation. However, the quality of the interferometric baseline network significantly influences the monitoring accuracy of InSAR technology. Therefore, optimizing the interferometric baseline is crucial for enhancing InSAR’s monitoring accuracy. Surface vegetation changes can disrupt the coherence between SAR images, introducing incoherent noise into interferograms and reducing InSAR’s monitoring accuracy. To address this issue, we propose and validate an optimization method for the InSAR baseline that considers changes in vegetation coverage (OM-InSAR-BCCVC) in the Yuanmou dry-hot valley. Initially, based on the imaging times of SAR image pairs, we categorize all interferometric image pairs into those captured during months of high vegetation coverage and those from months of low vegetation coverage. We then remove the image pairs with coherence coefficients below the category average. Using the Small Baseline Subset InSAR (SBAS-InSAR) technique, we retrieve surface deformation information in the Yuanmou dry-hot valley. Landslide identification is subsequently verified using optical remote sensing images. The results show that significant seasonal changes in vegetation coverage in the Yuanmou dry-hot valley lead to noticeable seasonal variations in InSAR coherence, with the lowest coherence in July, August, and September, and the highest in January, February, and December. The average coherence threshold method is limited in this context, resulting in discontinuities in the interferometric baseline network. Compared with methods without baseline optimization, the interferometric map ratio improved by 17.5% overall after applying the OM-InSAR-BCCVC method, and the overall inversion error RMSE decreased by 0.5 rad. From January 2021 to May 2023, the radar line of sight (LOS) surface deformation rate in the Yuanmou dry-hot valley, obtained after atmospheric correction by GACOS, baseline optimization, and geometric distortion region masking, ranged from −73.87 mm/year to 127.35 mm/year. We identified fifteen landslides and potential landslide sites, primarily located in the northern part of the Yuanmou dry-hot valley, with maximum subsidence exceeding 100 mm at two notable points. The OM-InSAR-BCCVC method effectively reduces incoherent noise caused by vegetation coverage changes, thereby improving the monitoring accuracy of InSAR.

Owing to advantages in synthesis, separation, structure determination, and low cost (compared to noble metal nanoclusters), Ag/Cu hydride clusters (and their alloys) have received increasing research interest in recent decades and have shown great potential in mediating reduction reactions and H2 storage applications. The atomic precision of the Ag/Cu hydride clusters with the combination of single-crystal X-ray diffraction, 1/2H nuclear magnetic resonance, electrospray ionization mass spectrometry, density functional theory, and particularly, single-crystal neutron diffraction, has provided pivotal information regarding its structural characteristics, facilitating a deep understanding of the inherent bonding principles therein. This review summarizes the research progress of atomically precise Ag/Cu hydride clusters (and their alloys) over the past three years (2021–2023), mainly focusing on the synthesis, structure analysis, and catalytic applications of the hydride clusters. We believe that this review can benefit the future design of different types of metal hydride clusters and aid in their application in various redox reactions.

During acute respiratory infections, women may concurrently receive human papillomavirus (HPV) and respiratory vaccines, as observed during the coronavirus disease 2019 (COVID-19) pandemic in China. However, few studies have assessed the safety of such concurrent administration, which could impact HPV vaccination schedules. This study analyzes the safety and optimal sequence of concurrent HPV and COVID-19 vaccinations. For this purpose, we surveyed women with both vaccines from January to October 2023 in Fujian Province, China. During this process, we collected vaccination history and adverse event (AE) data via telephone or interviews. Participants were grouped as Before, Concurrent, or After based on their vaccination sequence. A Chi-squared test, exact Fisher tests, and logistic regression were used to analyze the incidence of AEs and factors influencing vaccine safety. Overall, 1416 eligible participants were included. Although overall AE risk with the HPV vaccine was unaffected by vaccination sequence, individual AEs varied statistically between groups, including pain at the vaccination site (p < 0.001) and prolonged menstruation duration (p = 0.003). Based on the results, the optimal sequence would be to receive the HPV vaccine after the COVID-19 vaccine (After group). This insight may guide future emergency vaccination sequences for HPV and other respiratory infectious diseases.

Objective: Cholinesterase inhibitor (ChEIs) is the first-line drug for Alzheimer’s disease (AD). Understanding torsade de pointes (TdP)/QT prolongation with different ChEIs is essential for its safe and rational administration. This study aimed to evaluate the correlation between different ChEIs and TdP/QT prolongation.Methods: All ChEIs related TdP/QT prolongation cases were retrieved from the FAERS database using standard MedDRA query (SMQ) from the first quarter of 2004 to the third quarter of 2022. Disproportionality and sensitivity analysis were used to determine the signal of TdP/QT prolongation related to ChEIs.Results: 557 cases of TdP/QT prolongation related to 3 ChEIs were searched by SMQ. The patients were mostly elderly people, with markedly more female than male. The signals of TdP/QT prolongation for ChEIs were detected by disproportionality analysis, and the signal of Donepezil was the strongest. The sensitivity analysis results indicate a robust and stable correlation between these signals with ChEIs. TdP/QT prolongation usually occurs within 1 month after taking ChEIs. The drug with the highest frequency of combination with donepezil and galantamine is citalopram, and the drug with the highest frequency of combination with rivastigmine is atorvastatin.Conclusion: The signals of TdP/QT prolongation related to ChEIs were strong and stable. It is necessary to be vigilant about the TdP/QT prolongation of various ChEIs, especially in elderly women, the initial stage after taking ChEIs, and when ChEIs combining with drugs that could prolong the QT interval.

Objectives: Nasopharyngeal carcinoma (NPC) is an aggressive epithelial cancer. The expression of miR-186 is decreased in a variety of malignancies and can promote the invasion and metastasis of cancer cells. This study aimed to explore the role and possible mechanism of miR-186 in the metastasis and epithelial–mesenchymal transformation (EMT) of NPC. Methods: The expression of miR-186 in NPC tissues and cells was detected by RT-PCR. Then, miR-186 mimic was used to transfect NPC cell lines C666-1 and CNE-2, and cell activity, invasion and migration were detected by CCK8, transwell and scratch assay, respectively. The expression of EMT-related proteins was analyzed by western blotting analysis. The binding relationship between miR-186 and target gene Zinc Finger E-Box Binding Homeobox 1 (ZEB1) was confirmed by double luciferase assay. Results: The expression of miR-186 in NPC was significantly decreased, and transfection of miR-186 mimic could significantly inhibit the cell activity, invasion, and migration, and regulate the protein expressions of E-cadherin, N-cadherin and vimentin in C666-1 and CNE-2 cells. Further experiments confirmed that miR-186 could directly target ZEB1 and negatively regulate its expression. In addition, ZEB1 has been confirmed to be highly expressed in NPC, and inhibition of ZEB1 could inhibit the activity, invasion, metastasis and EMT of NPC cells. And co-transfection of miR-186 mimic and si-ZEB1 could further inhibit the proliferation and metastasis of NPC. Conclusion: miR-186 may inhibit the proliferation, metastasis and EMT of NPC by targeting ZEB1, and the miR-186/ZEB1 axis plays an important role in NPC.

Background: Drug-induced interstitial lung disease (DILD) is an increasingly common cause of morbidity and mortality. However, due to the lack of specificity, DILD detection remains an unsolved public health challenge. Objectives: For the first time, we aimed to examine DILD reports submitted to the Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS) to identify demographic characteristics and top drugs associated with DILD at a group level (including age, sex, drug class, and country stratification) and individual drug level. Design: A retrospective analysis of the FAERS database was examined by disproportionality analysis. Methods: We reviewed the FAERS database from 2004 to 2021, using search terms ‘interstitial lung disease’ and sorting cases by generic drug name. The reporting odds ratio, proportional reporting ratio, and Bayesian confidence propagation neural network were calculated as the measure of strength of association. Results: There were 32,821 DILD reports in the FAERS. After excluding reports without age, sex, or country data according to the specific measurement, the median age of patients was 68 (interquartile range: 59), 54.77% were male, and 46.00% of reports came from Japan. The top drug classes related to DILD in the FAERS were antineoplastic, followed by cardiovascular and antirheumatic agents, in varying order in different sexes. Fam-trastuzumab deruxtecan-nxki, ramucirumab, and eribulin were the top three drugs with the highest strength of association. We also found some drugs without DILD in the labels, such as amiodarone, temsirolimus, and ursodiol. There are significant differences in DILD reports in various countries. For example, the United States and France reported more cardiovascular agents, whereas Canada reported more antirheumatic agents. Conclusion: We found the top drugs and drug classes that were associated with DILD in the FAERS, which provides a real-world window for different ages, sexes, and countries to formulate precise pharmacovigilance policies.

ObjectivesThe characteristics of men who have sex with men (either exclusively or with both men and women; MSM) who engaged in casual sex among Chinese male university students have not been compared with the characteristics of men who have sex with only women (MSW). This information is important for tailoring targeted behavioral interventions to prevent human immunodeficiency virus (HIV)/sexually transmitted infection (STI) transmission in this subgroup of MSM.MethodsData were derived from a large cross-sectional electronic questionnaire survey conducted at 13 universities in Zhejiang Province, China, in 2018. Bivariate analyses were used to compare demographic, HIV-related psychosocial, and behavioral characteristics between MSM and MSW students who engaged in casual sex during the previous year. Proportion differences between the two groups and their 95% confidence intervals were analyzed.ResultsAmong the 583 sexually active male students who engaged in casual sex during the previous year, 128 and 455 were MSM and MSW, respectively. Compared with MSW students, larger proportions of MSM students reported knowing that male-to-male sexual behavior was the main mode of HIV transmission among Chinese students (62.5% vs. 45.5%), consenting to commercial sex (67.2% vs. 53.4%), wanting to know the HIV serostatus of partners before casual sex (65.8% vs. 51.3%), feeling at risk of HIV infection (40.5% vs. 11.8%), high condom-decision scale scores (55.3% vs. 42.6%), engaging in sex with ≥ 5 casual sex partners (44.6% vs. 25.9%), searching for casual partners online (89.2% vs. 51.3%), consuming alcohol before casual sex (64.8% vs. 45.0%), engaging in sex with regular partners (83.1% vs. 67.0%), engaging in commercial sex (54.2% vs. 26.4%), and visiting a clinic for voluntary counselling and testing (VCT) (16.4% vs. 8.4%). However, compared with MSW students, smaller proportions of MSM students reported knowing that consistent condom use could prevent HIV transmission (80.5% vs. 95.2%) and that VCT should be actively sought after risky sexual behavior (78.9% vs. 93.8%), using condoms sometimes/often (26.4% vs. 44.3%), and consistently using condoms (28.9% vs. 40.1%) while engaging in sex with casual partners.ConclusionsMSM students who engaged in casual sex were at a greater risk of HIV/STI transmission, compared with MSW students. Comprehensive interventions to address the risks of unprotected male-to-male sex, searching for casual sex partners online, and non-use of HIV testing services are needed to reduce the burden of HIV/STI transmission among this subgroup of MSM.

G2/M cell cycle checkpoint protein WEE1 kinase is a promising target for inhibiting tumor growth. Although various WEE1 inhibitors have entered clinical investigations, their therapeutic efficacy and safety profile remain unsatisfactory. In this study, we employed a comprehensive virtual screening workflow, which included Schrödinger-Glide molecular docking at different precision levels, as well as the utilization of tools such as MM/GBSA and Deepdock to predict the binding affinity between targets and ligands, in order to identify potential WEE1 inhibitors. Out of ten molecules screened, 50% of these molecules exhibited strong inhibitory activity against WEE1. Among them, compounds 4 and 5 showed excellent inhibitory activity with IC50 values of 1.069 and 3.77 nM respectively, which was comparable to AZD1775. Further investigations revealed that compound 4 displayed significant anti-proliferative effects in A549, PC9, and HuH-7 cells and could also induce apoptosis and G1 phase arrest in PC9 cells. Additionally, molecular dynamics simulations unveiled the binding details of compound 4 with WEE1, notably the crucial hydrogen bond interactions formed with Cys379. In summary, this comprehensive virtual screening workflow, combined with in vitro testing and computational modeling, holds significant importance in the development of promising WEE1 inhibitors.

AbstractPurpose Secondary hyperparathyroidism (SHPT) is a frequently encountered problem in patients with end-stage renal disease (ESRD) prior to renal transplantation (RTP), and the successful management of SPHP currently is challenging. In this study, we aimed to investigate the effectiveness of radiofrequency ablation (RFA) for SHPT as a bridge to RTP and to evaluate post-transplantation outcomes.Methods Patients with SHPT receiving RFA treatment were retrospectively reviewed, and those underwent RTP after ablation were enrolled. Serum parathyroid hormone (PTH), calcium, and phosphate levels were collected before ablation and at follow-up periods. The primary endpoints are PTH values at time of transplantation and at the final follow-up. The secondary endpoints were RFA-related complications, serum calcium and phosphate concentrations, and allograft function.Results Eleven patients with 43 enlarged parathyroid glands were treated with 16 RFA sessions and enrolled in the study. Complete ablation was achieved in all glands with transient hoarseness and hypocalcemia occurring in two and five of the treatments, respectively. At time of transplantation, serum PTH levels (246.7 ± 182.6 pg/mL) were significantly lower than that before RFA (1666.55 ± 874.48 pg/mL, p

ABSTRACTBackground Studies have shown acute flares of chronic hepatitis B (CHB) might be related to immunologic changes that occur during pregnancy. However, the indicators for predicting acute flares of CHB among pregnant women still need further study. We aimed to distinguish the relevance between serum levels of HBcrAg and acute flares of CHB in pregnant women in the immune-tolerant phase of chronic HBV infection after short-course antiviral therapy.Methods A total of 172 chronic HBV-infected pregnant women who were judged to be in the immune-tolerant phase were recruited in our research. All patients received short-course antiviral therapy with TDF. The biochemical, serological, and virological parameters were measured using standard laboratory procedures. The serum levels of HBcrAg were tested by ELISA.Results Fifty-two (30.2%) out of 172 patients had acute flares of CHB. At postpartum week 12 (TDF cessation), serum HBcrAg (OR, 4.52; 95% CI, 2.58–7.92) and HBsAg (OR, 2.52; 95% CI, 1.13–5.65) were associated with acute flares of CHB. The serum HBcrAg levels were beneficial for confirmation of patients with acute flares of CHB, with an area under the ROC curve of 0.84 (95% CI, 0.78–0.91).Conclusions For pregnant women with chronic HBV infection in the immune-tolerant phase, serum HBcrAg and HBsAg levels at postpartum week 12 were associated with acute flares of CHB after short-course antiviral therapy with TDF. The serum HBcrAg level can correctly identify acute flares of CHB and may be a predictor of the need for continuing antiviral therapy after 12 weeks postpartum.

ABSTRACTThe purpose of this study was to develop an effective and non-invasive nomogram for evaluating liver obvious inflammation in untreated HBeAg positive patients with chronic hepatitis B virus (HBV) infection. A nomogram was established on a model cohort of 292 treatment-naïve HBeAg positive patients with normal alanine aminotransferase (ALT ≤40 U/L) at Beijing Ditan Hospital from January 2008 to March 2018. Then the nomogram was prospectively validated in a cohort of 88 patients from July 2019 to May 2021. Calibration curves and Concordance index were used to evaluate the accuracy of prediction and identification performance of the model. In untreated HBeAg positive chronic hepatitis B virus infection patients with normal ALT, the formula for predicting liver inflammation was Logit (P) =-0.91-0.41×log10 (qHBeAg)+0.11×AST-0.01×PLT. The nomogram had C-index of 0.751 (95% CI, 0.688–0.815), indicating a good consistency between prediction and real observation on the model cohort. The validation cohort confirmed its good performance. In this study, liver inflammation nomograms based on HBeAg, AST, and PLT were established and verified in treatment-naïve HBeAg positive chronic HBV patients with normal ALT.

Abstract Background Exposure to air pollution is an important risk factor for intracerebral hemorrhage (ICH), which is a major cause of death worldwide. However, the relationship between ICH mortality and air quality improvement has been poorly studied. This study aims to evaluate the impact of the air pollution control policies in the Beijing-Tianjin-Hebei region on ICH mortality among Tianjin residents. Methods This study used an interrupted time series analysis. We fitted autoregressive integrated moving average (ARIMA) models to assess the changes in ICH deaths before and after the interventions of air pollution control policies based on the data of ICH deaths in Tianjin collected by the Tianjin Center for Disease Control and Prevention. Results Between 2009 and 2020, there were 63,944 ICH deaths in Tianjin, and there was an overall decreasing trend in ICH mortality. The intervention conducted in June 2014 resulted in a statistically significant (p = 0.03) long-term trend change, reducing the number of deaths from ICH by 0.69 (95% confidence interval [CI]: -1.30 to -0.07) per month. The intervention in October 2017 resulted in a statistically significant (p = 0.04) immediate decrease of 25.74 (95% CI: -50.62 to -0.85) deaths from ICH in that month. The intervention in December 2017 caused a statistically significant (p = 0.04) immediate reduction of 26.58 (95% CI: -52.02 to -1.14) deaths from ICH in that month. The intervention in March 2018 resulted in a statistically significant (p = 0.02) immediate decrease of 30.40 (95% CI: -56.41 to -4.40) deaths from ICH in that month. No significant differences were observed in the changes of male ICH mortality after any of the four interventions. However, female ICH deaths showed statistically significant long-term trend change after the intervention in June 2014 and immediate changes after the interventions in December 2017 and March 2018. Overall, the interventions prevented an estimated 5984.76 deaths due to ICH. Conclusion During the study period, some interventions of air pollution control policies were significantly associated with the reductions in the number of deaths from ICH among residents in Tianjin. ICH survivors and females were more sensitive to the protective effects of the interventions. Interventions for air pollution control can achieve public health gains in cities with high levels of air pollution.

Abstract The economic losses caused by uterine infections in ruminants have received increasing attention. Autophagy-related 7 (ATG7) has been demonstrated to be capable of regulating apoptosis, but surprisingly, ATG7 can both promote and inhibit apoptosis in different cellular contexts. However, the role of ATG7 in endometrial cell apoptosis during the postpartum period remains unclear. Herein, the location and expression of ATG7 was determined after mice were treated with lipopolysaccharide (LPS) in the uterus. The results showed that lipopolysaccharide (LPS) increased ATG7 expression in endometrial epithelial cells (EECs) but not endometrial stromal cells. The apoptosis of goat EECs was increased under LPS treatment, and LPS further led to an increase in bax expression and a decline in bcl-2 expression in goat EECs. Silencing of ATG7 inhibited goat EEC apoptosis with LPS treatment. The role of ATG7 in the regulation of goat EEC apoptosis was further confirmed by overexpression. ATG7 may serve as an essential regulatory factor in the process of endometrial epithelial cell apoptosis in ruminants under inflammatory injury. The findings help elucidate the pathogenesis of postpartum endometritis in ruminants.

A method was developed for the simultaneous determination of fat-soluble vitamins A, D2, D3 and α-, β-, γ-, δ-vitamin E in children's formula milk powder by combining online solid phase extraction (SPE) and two-dimensional liquid chromatography. The saponified samples were directly injected into the constructed system and purified by using the polymeric-based PLRP-S column as the SPE column. Then the target analytes were eluted in back-flush mode from the SPE column by SPE pump and refocused on the head of the first-dimensional column by using online dilution. Vitamins A and four E homologues were separated on a NuovaSilTM PFP column (4.6 mm×150 mm, 3 μm) as the first-dimensional column using a mobile phase consisting of methanol and 0.1% formic acid in water by gradient elution, and vitamins D2 and D3 were separated on a ChromCore PAH column (4.6 mm×150 mm, 3 μm) as the second-dimensional column using a mobile phase consisting of methanol and acetonitrile (90:10, v/v). The results showed good linearity in the range of 5.0~500.0 ng/mL for vitamin A, 1.0~100.0 ng/mL for vitamin D and 50.0~5000.0 ng/mL for vitamin E, and the correlation coefficients were all better than 0.9999. The limits of quantification for vitamins A, D2, D3 and α-, β-, γ-, δ-vitamins E were 5.11, 1.22, 1.25, 83.82, 57.27, 56.61, 54.82 µg/100 g, respectively. The spiked recoveries were 91.20%~104.47%, and the relative standard deviations were 0.94%~3.34%. The results show that the method established in this paper has the advantages of simple pretreatment, high automation, high analytical efficiency, high accuracy and good reproducibility, and is suitable for the determination of vitamins A, D and E in children's formula milk powder.

In recent years, some progress has been made in the exploration of Ordovician natural gas in the western Ordos Basin, among which, the Ordovician Kelimoli Formation has the highest degree of natural gas accumulation. However, the controlling factors for effective reservoir development are complicated, leading to unsatisfactory exploration effect. Based on the data of core observation, thin section identification, drilling and logging, the development types and controlling factors of effective reservoir in the Kelimoli Formation were systematically studied, and a development model of effective reservoir was established. The results show that the effective reservoir types of Kelimoli Formation in the western Ordos Basin mainly include dolomite intercrystal (dissolved) pore, limestone karst fracture and structural micro-fracture, and marginal platform granular pore type reservoir is locally developed. The development of effective reservoir was mainly controlled by sedimentary facies, diagenesis, paleokarst weathering and tectonic movement. The tidal flat facies and marginal platform facies provided the material basis for the original reservoir of the Kelimoli Formation, and on this basis, the dolomite intercrystal (dissolved) pore and marginal platform granular pore reservoirs were formed in the early diagenesis. In the stage of burial diagenesis, recrystallization obviously reformed the original dolomite reservoir, and the crystal framework became more stable. New intercrystal (dissolved) pores were formed or underwent secondary recrystallization. At the same time, the original structure of marginal platform granular pores was damaged, filled or improved, and the present marginal platform residual granular pores were formed. Paleo-karst weathering controlled the development of fracture-vuggy reservoirs in the middle and upper parts of the Kelimoli Formation, and high-yield wells were mainly drilled in the upper groove direction of the karst slope groove zone and karst highlands. The multi-stage tectonic movement continuously transformed and controlled the development of micro-fracture system, forming porous media reservoirs distributed around the fault zone. Therefore, it is a favorable direction for further exploration to find favorable facies belts of tidal flat facies and marginal platform facies, updip positions of karst paleo-geomorphology or high positions of fault zone.

Abstract Background Men who have sex with men and women (MSMW) are the most important bridge population for HIV transmission. Condom use plays an important role for HIV infection. However the predictors for condom ues with females are not well characterized. Methods This was a cross-sectional study. Participants were enrolled by four community-based organizations (CBOs) by offline (bathrooms, bars), and online (gay applications, chat room) from April to December 2019. Electronic questionnare was fulfilled after a face-to-face training led by CBOs. We identified predictors of inconsistent condom use with females by creating a risk score based on regression coefficients. We externally validated this score via an independent cross-sectional survey conducted in Zhejiang Province in 2021. A total of 917, 615 MSMW were included in analysis in 2019 and 2021, seperately. Results Among 917 MSMW, 73.2% reported heterosexual behavior in the prior 6 months and 38.3% reported inconsistent condom use with females (ICUF) over that time. Compared with heterosexual/unsure MSMW, bisexual MSMW reported more male and female sex partners, higher proportion of inconsistent condom use with males, less commercial sex with males (p

Objective: To explore the kidney yang deficiency pattern (KYDP) in a chronic kidney disease (CKD) rat model and the mechanisms underlying the effects of Zhenwu decoction (ZWD) by conducting transcriptomic and metabolomic analyses. Methods: Adriamycin (ADR) combined with hydrocortisone (HC) was used to induce CKD with KYDP in rats. ADR was injected into the tail vein twice. HC was injected intramuscularly for 8 weeks. ZWD was administered by gavage for 8 weeks. The general condition was observed, 24-h urine protein was detected, serum corticosterone, triiodothyronine, thyroxine, TSH, testosterone, cAMP, and cGMP levels were determined, and pathological analysis was conducted. Transcriptomic and metabolomic analyses were conducted to screen differentially expressed genes (DEGs), differentially expressed metabolites (DEMs), and differentially expressed pathways (DEPs). The core DEMs and DEGs were input to Metaboanalyst 5.0 to identify the pathways affected by ZWD. Results: In the HC group, KYDP symptoms were observed. Compared with control group, the levels of 24-h urine protein, TSH, and cGMP significantly increased (all P

Abstract Background The study aims to investigate the relationship between the volume-accumulated reflectivity (termed “integral”) on spectral domain optical coherence tomography (SD-OCT) and cone density on adaptive optics (AO) imaging. Methods In this cross-sectional study, both eyes of 32 healthy subjects and 5 patients with inherited retinal diseases (IRD) were studied. The parameter, integral, was defined as the volume-accumulated reflectivity values in a selected region on OCT images; integrals of the ellipsoid zone (EZ) and interdigitation zone (IZ) were measured at 2°, 3°, 4°, 5°and 6° eccentricity along the four meridians on fovea-centered OCT B-scans. Cone density in the same region was measured using a flood illumination adaptive optics camera RTX1. Results Integrals of EZ, IZ and cone density shared similar distribution patterns. Integral of the IZ was better correlated with cone density in both healthy people (r = 0.968, p

As members of doubly salient magnetless linear machines, linear variable flux reluctance (LVFR) and wound field flux reversal (LWFFR) machines inherit the merits of conventional magnetless linear machines such as low cost, high flux adjustment capability and high reliability. Furthermore, like linear switched reluctance machine, they have a very simple and compact long secondary, which are very attractive for long stroke applications. However, low force capability is their major defect. To solve this issue, new LVFR and LWFFR machine topologies were proposed in recent work, while lacking studies on their force improvement mechanism and further force evaluation. In this paper, LVFR and LWFFR machines with improved force performance are comparatively studied with the emphasis on their force capabilities. The operation principle of the two machines is analyzed based on magnetic field harmonics produced by flux modulation. Contributions of air-gap flux density harmonic components to no-load back electromagnetic forces of the two machines are analyzed and the average force equation is derived. Moreover, force capabilities of the both machines are investigated by means of the time-stepping finite-element analysis to verify the theoretical analysis.

Background: Metabolic dysfunction-associated fatty liver disease (MAFLD) is a significant health issue closely associated with multiple extrahepatic cancers. The association between MAFLD and clinical outcomes of endometrial cancer (EC) remains unknown. Methods: We retrospectively included 725 EC patients between January 2012 and December 2020. The odds ratios (ORs) were calculated using logistic regression analyses. Kaplan–Meier survival curves were used for survival analysis. Results: Among EC patients, the prevalence of MAFLD was 27.7% (201/725, 95% confidence interval (Cl) = 0.245–0.311). MAFLD was significantly associated with cervical stromal involvement (CSI) (OR = 1.974, 95% confidence interval (Cl) = 1.065–3.659, p = 0.031). There was a significant correlation between overall survival (OS) and CSI (HR = 0.31; 95%CI: 0.12–0.83; p = 0.020), while patients with MAFLD had a similar OS to those without MAFLD (p = 0.952). Moreover, MAFLD was significantly associated with CSI in the type I EC subgroup (OR = 2.092, 95% confidence interval (Cl) = 1.060–4.129, p = 0.033), but not in the type II EC subgroup (p = 0.838). Further logistic regression analysis suggested that the hepatic steatosis index (HSI) was significantly associated with CSI among type I EC patients without type 2 diabetes mellitus (T2DM) (OR = 1.079, 95% confidence interval (Cl) = 1.020–1.139, p = 0.012). Conclusions: About one-quarter of our cohort had MAFLD. MAFLD was associated with the risk of CSI in EC patients, and this association existed in type I EC patients but not in type II EC patients. Furthermore, the HSI can help predict CSI in type I EC patients without T2DM.

We propose in this paper an efficient algorithm based on the Fourier spectral-Galerkin approximation for the fourth-order elliptic equation with periodic boundary conditions and variable coefficients. First, by using the Lax-Milgram theorem, we prove the existence and uniqueness of weak solution and its approximate solution. Then we define a high-dimensional $ L^2 $ projection operator and prove its approximation properties. Combined with Céa lemma, we further prove the error estimate of the approximate solution. In addition, from the Fourier basis function expansion and the properties of the tensor, we establish the equivalent matrix form based on tensor product for the discrete scheme. Finally, some numerical experiments are carried out to demonstrate the efficiency of the algorithm and correctness of the theoretical analysis.

We demonstrate the regioselective growth of Au on Au nano-bipyramids, either with etching of the tips, uniform coating except the tips, or forming a single island on the axial tip or an island on the equatorial corner. Importantly, the regioselectivity not only arises from the local curvature, as suggested by the recent literature, but also critically depends on the extent of ligand coverage on the seed surface. It is important to consider the competitive growth together with the curvature–ligand interplay: when there are insufficient ligands, they bind preferentially to the sharp tip for high surface energy, so that the remaining growth materials are diverted elsewhere; when the bipyramid is fully covered by ligands, the growth then selectively occurs at the tips because of the larger gaps among the ligands there. Our results demonstrate the great potentials in the rational design and synthesis when constructing sophisticated hybrid structures for functional nanomaterials.

Abstract Objectives To identify genes that confer MS risk via the alteration of cis‐regulated protein abundance and verify their aberrant expression in human brain. Methods Utilizing a two‐stage proteome‐wide association study (PWAS) design, MS GWAS data (N = 41,505) was respectively integrated with two distinct human brain proteomes from the dorsolateral prefrontal cortex, including ROSMAP (N = 376) in the discovery stage and Banner (N = 152) in the confirmation stage. In the following, Bayesian colocalization analysis was conducted for GWAS and protein quantitative trait loci signals to prioritize candidate genes. Differential expression analysis was then used to verify the dysregulation of risk genes in white matter and gray matter for evidence at the transcription level. Results A total of 51 genes whose protein abundance had association with the MS risk were identified, of which 18 genes overlapped in the discovery and confirmation PWAS. Bayesian colocalization indicated six causal genes with genetic risk variants for the MS risk. The differential expression analysis of SHMT1 (PFDR = 4.82 × 10−2), FAM120B (PFDR = 8.13 × 10−4) in white matter and ICA1L (PFDR = 3.44 × 10−2) in gray matter confirmed the dysregulation at the transcription level. Further investigation of expression found SHMT1 significantly up‐regulated in white matter lesion, and FAM120B up‐regulated in both white matter lesion and normal appearing white matter. ICA1L was down‐regulated in both gray matter lesion and normal appearing gray matter. Interpretation Dysregulation of SHMT1, FAM120B and ICA1L may confer MS risk. Our findings shed new light on the pathogenesis of MS and prioritized promising targets for future therapy research.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related death worldwide that seriously threatens human health. Chronic infection of hepatitis virus B, C and D is closely related to the occurrence of HCC, about 80% HCC cases are caused by chronic viral hepatitis. Effective antiviral therapy can control liver inflammation, reduce the occurrence of HCC and reduce the recurrence of HCC after surgery treatment. In addition, during chemotherapy such as transarterial chemoembolization (TACE) or hepatic artery infusion chemotherapy (HAIC), targeted therapy and immunotherapy for HCC, antiviral therapy is also needed to prevent hepatitis virus reactivation. Therefore, antiviral therapy plays an important role in the prevention and treatment of HCC.

Background The reactivation of fetal γ-globin expression is an effective strategy for ameliorating the clinical symptoms of β-hemoglobinopathies. However, the mechanism of globin switching, especially the roles of long non-coding RNAs (lncRNAs) in this process, remains elusive. Methods We compared the in vivo transcriptome profiles of nucleated red blood cells (NRBCs) isolated from the umbilical cord blood of preterm and full-term newborns. We collected 75 umbilical cord blood samples and performed qPCR of the candidate genes. Results In this study, we identified 7,166 differentially expressed protein-coding genes, 3,243 differentially expressed lncRNAs, and 79 differentially expressed microRNAs. Our data show that the Fanconi anemia pathway and the H19/let-7/LIN28B axis may be involved in γ- to β-globin gene switching. Moreover, we constructed the hub gene network of the differentially expressed transcription factors. Based on qPCR, we found that BCL11A was differentially expressed based on biological sex. We also confirmed that H19 is differentially expressed and established the H19-related network to reveal the potential regulatory mechanisms. Conclusion We present the profiles of the in vivo transcriptome differences of NRBCs between preterm and full-term neonates for the first time, and provide novel research targets for β-hemoglobinopathies.

Semiconductor devices generally take advantage of the charge of electrons, whereas magnetic materials are used for recording information involving electron spin. To make use of both charge and spin of electrons in semiconductors, a high concentration of magnetic elements can be introduced in nonmagnetic III-V semiconductors to make magnetic semiconductor. In this work, Fe-Diamond was obtained with low solubility by modified microwave plasma chemical vapor deposition technique. Magnetic measurements revealed that the magnetic transition temperature from paramagnetic to ferromagnetic-like is above room temperature. The bandgap of Fe-Diamond is calculated to be 1.65 eV, which indicates that Fe-Diamond is a room temperature diluted ferromagnetic semiconductor.

The mining of open pit can easily cause geological disasters such as landslide and debris flow. It is widely acknowledged that communication technology could solve the existing problems in engineering practice from the aspects of disaster monitoring, deformation monitoring, landslide warning and emergency communication. This research paper introduces a fully integrated monitoring and early warning solution tailored for mining regions. By synergizing 6G and Global Navigation Satellite System (GNSS) technologies, the system effectively addresses signal transmission challenges in complex environments. The utilization of 6G’s high-speed, low-latency, and extensive connectivity capabilities enables efficient communication in these settings. The study focuses on a specific open-pit mine located in a cold region of China, utilizing it as a case study to demonstrate the system’s effectiveness in enhancing slope safety through comprehensive monitoring and early warning mechanisms. Apart from considering traditional dump characteristics and external factors, the system also introduces an innovative early warning index for detecting slope changes. Applying the Analytic Hierarchy Process (AHP) and Fuzzy comprehensive evaluation method ensures reliable evaluation results, facilitating slope assessment, monitoring, and early warning procedures in water-rich open-pit mines situated in cold areas.

Introduction Attention deficit is the most common cognitive impairment after stroke, which can significantly hinder the recovery of both other cognitive domains and motor functions. Increasing evidence suggests that the left dorsolateral prefrontal cortex (DLPFC) is related to non-spatial attention functions, which indicates that it may be a promising target of repetitive transcranial magnetic stimulation (rTMS) for treating poststroke non-spatial attention deficit. Theta burst stimulation (TBS) is a modified pattern of rTMS that delivers shorter stimulation times and exhibits superior therapeutic efficacy. This study aims to provide evidence regarding the efficacy of intermittent TBS (iTBS) over the left DLPFC to improve poststroke non-spatial attention deficits and elucidate the potential neurophysiological mechanisms.Methods and analysis In this single-centre, prospective, randomised, sham-controlled clinical trial, patients with non-spatial attention deficits (n=38) received 10 sessions of real iTBS (n=19) or sham iTBS (n=19) over the left DLPFC and a 30-min conventional attention training. Neuropsychological evaluations, electrophysiological examination and neuroimaging scan will be conducted at baseline, postintervention (second week) and 2-week follow-up (fourth week). The primary outcomes are the change in the Montreal Cognitive Assessment scores and the Digital Span Test scores from baseline to the end of the intervention (second week). The secondary outcomes comprise changes in magnetic resonance spectroscopy neuroimaging from baseline to the end of the intervention (second week) as well as attention test batteries (including tests of selective attention, sustained attention, divided attention and shifting attention) and ERP P300 from baseline to endpoint (fourth week).Ethics and dissemination This study has been approved by the Institutional Ethical Committee of Tongji Hospital (ID: TJ-IRB20230879). All participants will sign the informed consent. Findings will be published in peer-reviewed journals and conference presentations.Trial registration number ChiCTR2300068669.

In the spacer acquisition stage of CRISPR-Cas immunity, spacer orientation and protospacer adjacent motif (PAM) removal are two prerequisites for functional spacer integration. Cas4 has been implicated in both processing the prespacer and determining the spacer orientation. In Cas4-lacking systems, host 3′–5′ DnaQ family exonucleases were recently reported to play a Cas4-like role. However, the molecular details of DnaQ functions remain elusive. Here, we characterized the spacer acquisition of the adaptation module of the Streptococcus thermophilus type I-E system, in which a DnaQ domain naturally fuses with Cas2. We presented X-ray crystal structures and cryo-electron microscopy structures of this adaptation module. Our biochemical data showed that DnaQ trimmed PAM-containing and PAM-deficient overhangs with different efficiencies. Based on these results, we proposed a time-dependent model for DnaQ-mediated spacer acquisition to elucidate PAM removal and spacer orientation determination in Cas4-lacking CRISPR-Cas systems.

Objective To investigate the relationship between the neutrophil-to-lymphocyte ratio and chronic obstructive pulmonary disease complicated with pulmonary hypertension (COPD + PH). Methods We retrospectively analyzed clinical data from 242 COPD patients at our hospital from July 2018 to July 2019. Patients underwent examinations including blood analysis, C-reactive protein, N-terminal brain natriuretic peptide (BNP), pulmonary function, and cardiac color ultrasound. Results Patients were divided into the COPD and COPD + PH groups using pulmonary arterial pressure (

The relatively new discipline of pharmacovigilance (PV) aims to monitor the safety of drugs throughout their evolution and is essential to discovering new drug risks. Due to their specific and complex physiology, children, pregnant women, and elderly adults are more prone to adverse drug reactions (ADRs). Additionally, the lack of clinical trial data exacerbates the challenges faced with pharmacotherapy in these populations. Elderly patients tend to have multiple comorbidities often requiring more extensive medication, which adds additional challenges for healthcare professionals (HCPs) in delivering safe and effective pharmacotherapy. Clinical trials often have inherent limitations, including insufficient sample size and limited duration of research; as some ADRs are attributed to long-term use of a drug, these may go undetected during the course of the trial. Therefore, the implementation of PV is key to insuring the safe and effective use of drugs in special populations. We conducted a thorough review of the scientific literature on PV systems across the European Union, the United States, and China. Our review focused on basic physiological characteristics, drug use, and PV for specific populations (children, pregnant women, and the elderly). This article aims to provide a reference for the development of follow-up policies and improvement of existing policies as well as provide insight into drug safety with respect to patients of special populations.