Doxycycline inhibits neurotropic enterovirus proliferation in vitro.

Human enteroviruses (EVs) represent a global public health concern due to their association with a range of serious pediatric illnesses. Despite the high morbidity and mortality exerted by EVs, no broad-spectrum antivirals are currently available. Herein, we presented evidence that doxycycline can inhibit in vitro replication of various neurotropic EVs, including enterovirus A71 (EV-A71), enterovirus D68 (EV-D68), and coxsackievirus (CV)-A6, in a dose-dependent manner. Further investigations indicated that the drug primarily acted at the post-entry stage of virus infection in vitro, with inhibitory effects reaching up to 89% for EV-A71 when administered two hours post-infection. These findings provide valuable insights for the development of antiviral drugs against EV infections.

Construction and evaluation of near-infrared fluorescent probes for imaging lipid droplet and lysosomal viscosity.

Microenvironmental viscosity is a crucial parameter for biological systems, and its abnormal fluctuations are closely associated with various functional disorders and diseases. However, it is still important and urgent to develop improved near-infrared fluorescent probes for micro-viscosity with dual-organelle targeting properties, low background noise, and high sensitivity. Herein, two BODIPY-based small-molecule fluorescent probes were designed and synthesized, which were explored for their viscosity- and polarity-responsive properties, and were further applied to imaging sub-cellular viscosity in living cells. Interestingly, BSZ-Ph and BSZ-R displayed near-infrared fluorescence (more than 650 nm) and were sensitive to environmental viscosity and polarity due to the introduction of a benzothiazole at the 2-position and electron-rich aniline groups at the 5-position of the BODIPY core, respectively. The fluorescence intensity increased exponentially with the viscosity changes. Furthermore, the probe BSZ-Ph could successfully target lipid droplets and image cellular viscosity changes by treating lipopolysaccharides (LPS) and nystatin. Comparatively, the probe BSZ-R could successfully target the dual organelles of lipid droplets and lysosomes and image cellular viscosity changes by treating LPS and monensin. Therefore, in this work, we reported two new BODIPY-based near-infrared fluorescent probes, BSZ-Ph and BSZ-R, for cellular viscosity imaging, which could target lipid droplets and the dual organelles of lysosomes and lipid droplets, respectively. The study could provide a reference for the future development of fluorescent probes for viscosity in lipid droplets and lysosomes.

Characterization of humoral immune responses against SARS-CoV-2 accessory proteins in infected patients and mouse model.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, encodes several accessory proteins that have been shown to play crucial roles in regulating the innate immune response. However, their expressions in infected cells and immunogenicity in infected humans and mice are still not fully understood. In this study, we detected accessory protein-specific antibodies in COVID-19 patients' sera using various techniques, including Luciferase Immunoprecipitation System (LIPS), Immunofluorescence assay (IFA), and Western blot (WB). Proteins 3a, 3b, 7b, 8 and 9c specific antibodies can be detected by LIPS, but only protein 3a antibody was detected by IFA or WB. And antibodies against protein 3a and 7b only detected in ICU patients, which may serve as a marker for predicting the disease progression. Further, we investigated the expression of accessory proteins in SARS-CoV-2-infected cells and identified the expressions of proteins 3a, 6, 7a, 8, and 9b. We also analyzed their ability to induce antibodies in immunized mice and found that only proteins 3a, 6, 7a, 8, 9b and 9c were able to induce measurable antibody productions, but these antibodies lacked neutralizing activities and did not protect mice from SARS-CoV-2 infection. Our findings validate the expression of SARS-CoV-2 accessory proteins and elucidate their humoral immune response, providing a basis for the protein detection assays and their role in pathogenesis.

Unveiling disguised toxicity: A novel pre-processing module for enhanced content moderation.

This study introduces "Specialis Revelio," a sophisticated text pre-processing module aimed at enhancing the detection of disguised toxic content in online communications. Through a blend of conventional and novel pre-processing methods, this module significantly improves the accuracy of existing toxic text detection tools, addressing the challenge of content that is deliberately altered to evade standard detection methods.•Integration with Existing Systems: "Specialis Revelio" is designed to augment popular toxic text classifiers, enhancing their ability to detect and filter toxic content more effectively.•Innovative Pre-processing Methods: The module combines traditional pre-processing steps like lowercasing and stemming with advanced strategies, including the handling of adversarial examples and typo correction, to reveal concealed toxicity.•Validation through Comparative Study: Its effectiveness was validated via a comparative analysis against widely used APIs, demonstrating a marked improvement in the detection of various toxic text indicators.

Explainable machine-learning predictions for catalysts in CO2-assisted propane oxidative dehydrogenation.

Propylene is an important raw material in the chemical industry that needs new routes for its production to meet the demand. The CO2-assisted oxidative dehydrogenation of propane (CO2-ODHP) represents an ideal way to produce propylene and uses the greenhouse gas CO2. The design of catalysts with high efficiency is crucial in CO2-ODHP research. Data-driven machine learning is currently of great interest and gaining popularity in the heterogeneous catalysis field for guiding catalyst development. In this study, the reaction results of CO2-ODHP reported in the literature are combined and analyzed with varied machine learning algorithms such as artificial neural network (ANN), k-nearest neighbors (KNN), support vector regression (SVR) and random forest regression (RF)and were used to predict the propylene space-time yield. Specifically, the RF method serves as a superior performing algorithm for propane conversion and propylene selectivity prediction, and SHapley Additive exPlanations (SHAP) based on the Shapley value performs fine model interpretation. Reaction conditions and chemical components show different impacts on catalytic performance. The work provides a valuable perspective for the machine learning in light alkane conversion, and helps us to design catalyst by catalytic performance hidden in the data of literatures.

Chinese Society of Cardiology guidelines on the diagnosis and treatment of adult fulminant myocarditis.

Fulminant myocarditis is an acute diffuse inflammatory disease of myocardium. It is characterized by acute onset, rapid progress and high risk of death. Its pathogenesis involves excessive immune activation of the innate immune system and formation of inflammatory storm. According to China's practical experience, the adoption of the "life support-based comprehensive treatment regimen" (with mechanical circulation support and immunomodulation therapy as the core) can significantly improve the survival rate and long-term prognosis. Special emphasis is placed on very early identification,very early diagnosis,very early prediction and very early treatment.

The association of plasma connective tissue growth factor levels with left ventricular diastolic dysfunction in patients with overt hyperthyroidism.

Background: Left ventricular (LV) diastolic dysfunction is an independent predictor of future cardiovascular events. Early detection of patients with LV diastolic dysfunction can improve clinical outcomes through active management. However, the assessment of diastolic function is very complicated, and there are currently lack of effective biomarkers to assess the risk of LV diastolic dysfunction. Connective tissue growth factor (CTGF) plays a significant role in cardiac remodeling and dysfunction. We aimed to investigate the associations between plasma CTGF level and the risk of LV diastolic dysfunction in this study and judge its effectiveness in diagnosing LV diastolic dysfunction. Methods: A total of 169 patients with overt hyperthyroidism were included. LV diastolic function was evaluated and the subjects were divided into normal LV diastolic function group and LV diastolic dysfunction group. Routine clinical medical data, biochemical data, thyroid related parameters and echocardiographic parameters were recorded for analysis. Results: Compared with normal LV diastolic function group, the LV diastolic dysfunction group had higher age and BMI, as well as lower heart rate, lower serum albumin, lower eGFR, higher serum TgAb and BNP level, and the incidences of hypertension were also higher (all P <0.05). Circulating plasma CTGF levels in the LV diastolic dysfunction group were significantly higher (normal LV diastolic function group: 7.026 [5.567-8.895], LV diastolic dysfunction group: 8.290 [7.054-9.225] ng/ml, median [(Interquartile range)], P = 0.004); Compared with the lowest quartile group, the crude odds ratios (OR) of LV diastolic dysfunction in the second, third, and fourth quartile group were 3.207, 5.032 and 4.554, respectively (all P<0.05). After adjustment for the potentially confounding variables, the adjusted OR values of the third and fourth quartile group had no obvious change. The results of ROC showed that the plasma CTGF had the largest area under the ROC curve, and the value was 0.659 (P = 0.005). Conclusion: The level of circulating plasma CTGF in the LV diastolic dysfunction group was significantly increased. Plasma CTGF level is an independent risk factor for LV diastolic dysfunction. Compared with serum BNP level, the plasma CTGF level may have auxiliary diagnostic value for LV diastolic dysfunction in hyperthyroid patients.

Postoperative MRI Findings Following PELD and Their Correlations with Clinical Prognosis are Investigated by Injecting Contrast into Annulus Fibrosus Intraoperatively.

Objective: To validate whether a residual mass demonstrated on early postoperative MR after percutaneous endoscopic lumbar discectomy (PELD) is indeed an intraoperatively retained annulus fibrosus, and explore the correlation between imaging changes in the residual mass and clinical prognosis of patients. Methods: A prospective study of 118 patients were included. During surgery, a contrast medium, Gadopentetate Dimeglumine, was injected around the ruptured annulus fibrosus. The intensity of the T2 signal, the size of the remaining mass (SR), and the cross-sectional area of the spinal canal (SCSA), VAS, and ODI were assessed at preoperative, 1-h (7-day), 6-month, and 12-month postoperative intervals. Based on VAS at 7 days post-surgery, patients were classified into either a non-remission group (Group A, VAS > 3) or a remission group (Group B, VAS ≤ 3). Results: Six patients who developed recurrent LDH were excluded. A residual mass was detected on MRI 1 h after surgery in 94.6% (106/112). During one year of follow-up, 90.1% (101/112) of the patients displayed fibrous annulus remodeling, although 68.7% (77/112) still exhibited herniation. Significant differences were found in the ODI between Groups A and B one week after surgery (p < 0.001). However, no significant differences were observed in T2 signal intensity, SR, and SCSA at 1-h, 6-month and 12-month post-surgery (p > 0.05) between the two groups. In a multiple linear regression analysis, early postoperative ODI changes were associated with T2 signal (B = -10.22, sig < 0.05), long-term changes were associated with alterations in SR (B = 5.63, sig < 0.05) and SCSA (B = -0.13, sig < 0.05). Conclusion: The residual mass observed in early postoperative MR images after PELD was the retained annulus fibrosus intraoperatively. Short-term changes in clinical symptoms after PELD were linked to T2 signal intensity, while long-term changes were associated with changes in SR and SCSA.

Fundamentals of Unanticipated Efficiency of Gd2O3-based Catalysts in Oxidative Coupling of Methane.

Improving the selectivity in the oxidative coupling of methane to ethane/ethylene poses a significant challenge for commercialization. The required improvements are hampered by the uncertainties associated with the reaction mechanism due to its complexity. Herein, we report about 90 % selectivity to the target products at 11 % methane conversion over Gd2O3-based catalysts at 700 °C using N2O as the oxidant. Sophisticated kinetic studies have suggested the nature of adsorbed oxygen species and their binding strength as key parameters for undesired methane oxidation to carbon oxides. These descriptors can be controlled by a metal oxide promoter for Gd2O3.

Management of nocturnal hypertension: An expert consensus document from Chinese Hypertension League.

Nocturnal hypertension is highly prevalent among Chinese and Asian populations, which is mainly attributed to high salt intake and high salt sensitivity. Nocturnal hypertension increases the risk of cardiovascular and all-cause mortality, independent of daytime blood pressure (BP). However, it can usually be detected by 24-h ambulatory BP monitoring, rather than routine office or home BP measurement, thus is often underdiagnosed in clinical practice. Currently, no specific guidance is available for the management of nocturnal hypertension in China or worldwide. Experts from the Chinese Hypertension League summarized the epidemiologic and pathophysiologic characteristics and clinical phenotype of nocturnal hypertension and provided consensus recommendations on optimal management of nocturnal hypertension, with the goal of maximally reducing the cardiovascular disease risks. In this consensus document, 24-h ABPM is recommended for screening and diagnosis of nocturnal hypertension, especially in the elderly, patients with diabetes, chronic kidney diseases, obstructive sleep apnea and other conditions prone to high nocturnal BP. Lifestyle modifications including salt intake restriction, exercise, weight loss, sleep improvement, and mental stress relief are recommended. Long-acting antihypertensive medications are preferred for nocturnal and 24-h BP control. Some newly developed agents, renal denervation, and other device-based therapy on nocturnal BP reduction are evaluated.

Aberrant structural rich club organization in temporal lobe epilepsy with focal to bilateral tonic-clonic seizures.

OBJECTIVE: The purpose of this study was to assess the differences of topological characteristic and rich club organization between temporal lobe epilepsy (TLE) patients with focal seizure (FS) only and those with focal to bilateral tonic-clonic seizures (FBTCS). METHODS: We recruited 130 unilateral TLE patients, of which 57 patients with FS only and 73 patients with both FS and FBTCS, and 68 age- and gender-matched healthy controls (HC). Whole-brain networks were constructed based on diffusion weighted imaging data. Graph theory was applied to quantify the topological network metrics and rich club organization. Network-based statistic (NBS) analysis was administered to investigate the difference in edge-wise connectivity strength. The non-parametric permutation test was applied to evaluate the differences between groups. Benjamini-Hochberg FDR at the alpha of 5% was carried out for multiple comparations. RESULTS: In comparison with HC, both the FS and FBTCS group displayed a significant reduction in whole-brain connectivity strength and global efficiency. The FBTCS group showed lower connectivity strength both in the rich club and feeder connections compared to HC. The FS group had lower connectivity strength in the feeder and local connections compared to HC. NBS analysis revealed a wider range of decreased connectivity strength in the FBTCS group, involving 90% of the rich club regions, mainly affecting temporal-subcortical, frontal-parietal, and frontal-temporal lobe, the majority decreasing connections were between temporal lobe and stratum. While the decreased connectivity strength in the FS group were relatively local, involving 50% of rich club regions, mainly concentrated on the temporal-subcortical lobe. CONCLUSIONS: Network integration was reduced in TLE. TLE with FBTCS selectively disrupted the rich club regions, while TLE with FS only were more likely to affect the non-rich club regions, emphasizing the contribution of rich club organization to seizure generalization.

Initial screening for occult congenital ectopia lentis based on ocular biological parameters in preschool children.

BACKGROUND: This study aimed to identify an initial screening tool for congenital ectopia lentis (CEL) by comparing ocular biological parameters in children with myopia. METHODS: A retrospective case-control study was conducted at one tertiary referral centre, from October 2020 to June 2022. Axial length (AL), corneal curvature (CC), refractive astigmatism (RA), corneal astigmatism (CA), internal astigmatism (IA), the difference between the axis of RA and CA [AXIS(RA-CA)], white-to-white corneal diameter (WTW), and axial length-corneal radius ratio (AL/CR) were compared in 28 eyes of CEL patients, and 60 eyes of myopic patients matched for age and refraction. The spherical equivalent of each eye was < -3.00 D. Area under the curve (AUC) of the receiver operating characteristic curves were calculated. RESULTS: The differences in RA, AL, mean keratometry (Kmed), maximum keratometry (Kmax), minimum keratometry (Kmin), CA, IA, AXIS(RA-CA), WTW, and AL/CR between the CEL and myopic groups were statistically significant (p < 0.05; p < 0.001; p < 0.001; p < 0.001; p < 0.001; p < 0.05; p < 0.001; p < 0.001; p < 0.001; p < 0.001, respectively). In logistic regression analysis RA, IA, AXIS(RA-CA), and AL/CR were significantly associated with CEL (p < 0.05). AUCs for RA, IA, AXIS(RA-CA), and AL/CR were 0.694, 0.853, 0.814, and 0.960, respectively. AUCs for AL/CR in SE< -6.00 D subgroup was 0.970, and 0.990 in -6.00 D ≤ SE < -3.00 D group. An AL/CR < 3.024 was the optimal cut-off point differentiating the CEL and control groups (sensitivity, 92.9%; specificity, 88.30%). CONCLUSIONS: A smaller AL/CR could identify CEL in children with myopia. An AL/CR cut-off value of 3.024 may be the most sensitive and specific parameter for the differential diagnosis of CEL in patients with mild to high myopia.

Single-cell and bulk RNA sequencing reveals Anoikis related genes to guide prognosis and immunotherapy in osteosarcoma.

Anoikis resistance, a notable factor in osteosarcoma, plays a significant role in tumor invasion and metastasis. This study seeks to identify a distinct gene signature that is specifically associated with the anoikis subcluster in osteosarcoma. Clinical, single-cell, and transcriptional data from TARGET and GEO datasets were used to develop a gene signature for osteosarcoma based on the anoikis subcluster. Univariate Cox and LASSO regression analyses were employed. The signature's predictive value was evaluated using time-dependent ROC and Kaplan-Meier analyses. Functional enrichment analyses and drug sensitivity analyses were conducted. Validation of three modular genes was performed using RT-qPCR and Western blotting. Signature (ZNF583, CGNL1, CXCL13) was developed to predict overall survival in osteosarcoma patients, targeting the anoikis subcluster. The signature demonstrated good performance in external validation. Stratification based on the signature revealed significantly different prognoses. The signature was an independent prognostic factor. The low-risk group showed enhanced immune cell infiltration and improved immune function. Drug sensitivity analysis indicated efficacy of chemotherapy agents. Prognostic nomograms incorporating the signature provided greater predictive accuracy and clinical utility. Signatures related to the anoikis subcluster play a significant role in osteosarcoma progression. Incorporating these findings into clinical decision-making can improve osteosarcoma treatment and patient outcomes.

Optimization of Steelmaking Energy Efficiency Scheduling Based on an Equipment Set Shutdown Strategy.

The steel industry accounts for a large proportion of power consumption in industries. To greatly reduce the power consumption of production, it is urgent to adjust and optimize the steelmaking production mode. The paper combines production scheduling with equipment energy efficiency indicators, establishing an optimization model for steelmaking energy efficiency scheduling and determining the shutdown strategy of steelmaking equipment sets. Taking two equipment sets of a company processing the same batch of steel as an example, this paper calculates that the unit energy consumption under the optimal scheduling scheme is 79.492 and 22.056 kWh, respectively. The energy consumption of the former to complete the production task is greater than that of the latter. Therefore, by choosing to shut down this equipment set, a total of 65 038.2 kWh of electricity can be saved. Industrial examples were executed to validate the effectiveness of the model, and the results showed that the proposed method can obtain optimal solutions in a short period of time and significantly reduce energy consumption in the workshop. This study first combines scheduling issues with equipment energy efficiency indicators to provide a basis for energy consumption decisions.

Optimizing irrigation strategies for sustainable crop productivity and reduced groundwater consumption in a winter wheat-maize rotation system.

Inefficient irrigation practices have hindered crop yields, wasted irrigation water resources, and posed threats to groundwater levels and agricultural sustainability. This study evaluated different irrigation strategies for a winter wheat-summer maize rotation system to identify sustainable practices for maintaining yields while reducing groundwater depletion. A two-year field experiment was conducted, implementing three optimized irrigation strategies during the winter wheat season: I-4 (irrigated until the soil water content (SWC) of the 40 cm soil layer reaches 60% of field capacity (FC), I-6 (irrigated until the SWC of the 60 cm soil layer reaches 80% FC), and a rainfed (R) as control. Irrigation was repeated when the SWC dropped to the specified level. No irrigation level was used during the summer maize season, except for irrigation after sowing that ensuring the normal emergence of maize. WHCNS (Water Heat Carbon Nitrogen Simulator) model was developed to simulate soil water dynamics, field water consumption, and yield of both crops. The result indicated WHCNS model accurately simulated water dynamics, consumption, and grain yield. Compared to R treatment, the I-4 treatment significantly increased annual crop yield by 19.83%-28.65% (p < 0.05), while maintaining similar crop water productivity. Furthermore, the I-4 treatment achieved comparable yields to the I-6 treatment, but with a 33.91% reduction in irrigation water use, resulting in a 33.46% increase in crop water productivity and a 90.53% increase in irrigation water productivity. From a sustainable perspective, the I-4 treatment effectively reduced field water losses and maintained relatively high soil water storage, particularly in the topsoil, which was beneficial for the early growth of subsequent crops. The R treatment greatly contributed to groundwater recharge when precipitation was sufficient, while it led to severe yield losses. Overall, under the condition of annual rotation planting systems, the I-4 treatment sustainably maintained yields with less irrigation, decreasing groundwater consumption. This approach could conserve regional water resources and groundwater table while upholding agricultural productivity and achieving system sustainable water use.

Central diastolic blood pressure, plasma aldosterone and uric acid are associated with microalbuminuria in essential hypertension: a case-control study.

OBJECTIVE: To study the development of microalbuminuria (MAU) in essential hypertension (EHT), we investigated the association of MAU with central blood pressure (CBP), direct renin concentration (DRC), plasma aldosterone (PA), and uric acid (UA). METHOD: We determined 24 h-urinary albumin excretion (24 h-UAE) in patients with EHT who were hospitalized at TEDA International Cardiovascular Hospital from June 2020 to May 2022. We defined MAU as 24 h-UAE in the range of 30 mg/24 h to 300 mg/24 h. Univariate and multivariate analyses were conducted to determine the associations of MAU with CBP, DRC, PA, and UA in EHT, considering demographic and clinical information. We also plotted receiver operating characteristic curves (ROCs) for predicting MAU using these results. RESULTS: More than a quarter of patients (26.5%, 107/404, 95% CI: 22.2-31.1%) were diagnosed with MAU in EHT. A higher body mass index (BMI), longer duration of hypertension, and higher severity were associated with MAU. Also, nearly 10% more creatinine levels were recorded in the MAU group than in the control group (69.5 ± 18.7 µmol/L vs. 64.8 ± 12.5 µmol/L, P = 0.004). The increase was also observed for PA (15.5, 9.7-20.6 ng/dL vs. 12.3, 9.0-17.3 ng/dL, P = 0.024) and UA (419.8 ± 105.6 µmol/L vs. 375.1 ± 89.5 µmol/L, P < 0.001) in the MAU group compared to that in the control group. Several variables were associated with MAU, including central diastolic blood pressure (CDBP) (OR = 1.017, 95% CI: 1.002-1.032, P = 0.027), PA (OR = 1.043, 95% CI: 1.009-1.078, P = 0.012) and UA (OR = 1.005, 95% CI: 1.002-1.008, P < 0.001). For MAU prediction, the area under the curve (AUC) was 0.709 (95% CI: 0.662-0.753; P < 0.001) when CDBP, PA, and UA were used in combination, and the optimal probability of the cut-off value was 0.337. CONCLUSION: We found that CDBP, PA, and UA, used for MAU prediction, might be associated with its development during EHT.

Maternal exposure to hyperbaric oxygen at the preimplantation stages increases apoptosis and ectopic Cdx2 expression and decreases Oct4 expression in mouse blastocysts via Nrf2-Notch1 upregulation and Nf2 downregulation.

BACKGROUND: The environmental oxygen tension has been reported to impact the blastocyst quality and cell numbers in the inner cell mass (ICM) during human and murine embryogenesis. While the molecular mechanisms leading to increased ICM cell numbers and pluripotency gene expression under hypoxia have been deciphered, it remains unknown which regulatory pathways caused the underweight fetal body and overweight placenta after maternal exposure to hyperbaric oxygen (HBO). RESULTS: The blastocysts from the HBO-exposed pregnant mice revealed significantly increased signals of reactive oxygen species (ROS) and nuclear Nrf2 staining, decreased Nf2 and Oct4 expression, increased nuclear Tp53bp1 and active caspase-3 staining, and ectopic nuclear signals of Cdx2, Yap, and the Notch1 intracellular domain (N1ICD) in the ICM. In the ICM of the HBO-exposed blastocysts, both Nf2 cDNA microinjection and Nrf2 shRNA microinjection significantly decreased the ectopic nuclear expression of Cdx2, Tp53bp1, and Yap whereas increased Oct4 expression, while Nrf2 shRNA microinjection also significantly decreased Notch1 mRNA levels and nuclear expression of N1ICD and active caspase-3. CONCLUSION: We show for the first time that maternal exposure to HBO at the preimplantation stage induces apoptosis and impairs ICM cell specification via upregulating Nrf2-Notch1-Cdx2 expression and downregulating Nf2-Oct4 expression.

Body mass index, neck circumference, and hypertension: a prospective cohort study.

Objective: This study aimed to investigate the association between BMI combined with neck circumference and the risk of hypertension. Methods: We selected participants from the Kailuan study in 2014 who were normotensive as our research subjects. We compared the risk of hypertension among individuals in group 1 (non-obese with low neck circumference), group 2 (non-obese with high neck circumference), group 3 (obese with low neck circumference), and group 4 (obese with high neck circumference). Results: After a median observation period of 3.86 years, hypertension occurred in 13,383 participants. Subjects in Group 2, 3, and 4 had significantly higher risks of hypertension compared to Group 1, with hazard ratios (HRs) of 1.066 (95% CI: 1.025, 1.110), 1.322 (95% CI: 1.235, 1.415), and 1.422 (95% CI: 1.337, 1.512), respectively. Additionally, adding BMI to a conventional model had a greater incremental effect on predicting hypertension compared to adding neck circumference alone. However, considering both BMI and neck circumference together further improved the prediction of hypertension. Conclusion: Individuals with both high BMI and high neck circumference face a higher risk of hypertension. Moreover, BMI is a superior predictor of hypertension risk compared to neck circumference, but using both of these measures can further enhance the accuracy of hypertension risk prediction.

Lactylation of METTL16 promotes cuproptosis via m6A-modification on FDX1 mRNA in gastric cancer.

Cuproptosis, caused by excessively high copper concentrations, is urgently exploited as a potential cancer therapeutic. However, the mechanisms underlying the initiation, propagation, and ultimate execution of cuproptosis in tumors remain unknown. Here, we show that copper content is significantly elevated in gastric cancer (GC), especially in malignant tumors. Screening reveals that METTL16, an atypical methyltransferase, is a critical mediator of cuproptosis through the m6A modification on FDX1 mRNA. Furthermore, copper stress promotes METTL16 lactylation at site K229 followed by cuproptosis. The process of METTL16 lactylation is inhibited by SIRT2. Elevated METTL16 lactylation significantly improves the therapeutic efficacy of the copper ionophore- elesclomol. Combining elesclomol with AGK2, a SIRT2-specific inhibitor, induce cuproptosis in gastric tumors in vitro and in vivo. These results reveal the significance of non-histone protein METTL16 lactylation on cuproptosis in tumors. Given the high copper and lactate concentrations in GC, cuproptosis induction becomes a promising therapeutic strategy for GC.

Case report: Heterozygous mutation in HTRA1 causing typical cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy.

Background: Cerebral autosomal recessive arteriopathy with subcortical infarcts and leukoencephalopathy (CARASIL) is an autosomal recessive disorder characterized by baldness, recurrent ischemic stroke, lumbago, headache, and dementia which is closely related to homozygous mutations of the high-temperature requirement serine peptidase A1 (HTRA1) gene. Heterozygous mutations of HTRA1 are usually considered to be non-pathogenic. Although it has been revealed that only a few patients with heterozygous mutations could present some manifestations, their clinical symptoms were atypical, milder, and always with a lower frequency of extra-neurological features. Here, a rare patient with heterozygous mutation of HTRA1 who had all typical features of CARASIL as well as severe clinical symptoms and rapid progression was initially reported in our study. Case presentation: A 43-year-old female patient presented with a gradual onset of headache and cognitive decline. As time progressed, her headache intensified and symptoms of dementia began to manifest gradually. During her early years, she had thinning hair and subsequently experienced two occurrences of ischemic strokes in her thirties. Furthermore, she also had a history of lumbago and urinary retention before visiting our hospital. The patient's magnetic resonance imaging revealed the presence of widespread white matter lesions, infarctions, and microbleeds, in addition to lumbar disc herniation and degenerative lesions. The observed clinical characteristics had a strong correlation with CARASIL, and the patient was diagnosed with a heterozygous missense mutation of 905G>A (Arg302Gln) in the HTRA1 gene. The patient has been under continuous follow-up for a duration exceeding 3 years subsequent to her release from the hospital. She underwent cystostomy, and symptoms of bulbar paralysis developed in a progressive way. Currently, there has been a notable decrease in motor function and activities of daily living, resulting in the individual being confined to bed for a duration exceeding 1 year. Conclusion: This case suggests that patients carrying a heterozygous mutation in G905A may also have typical clinical features of CARASIL, which allows us to have a more comprehensive understanding of CARASIL.