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IntroductionDue to the high mortality rate and increasing severity of antibiotic resistance, there is a growing interest in new treatments for Klebsiella pneumoniae (KP)-induced pneumonia. Research has shown that the single herbs of SiHuangQingXinWan (SHQXW) are effective in treating pneumonia caused by KP. The PI3K/AKT signaling pathway has garnered attention for its potential role in the management of bacterial infections. This study aimed to evaluate the anti-pneumonia effect of SHQXW and to investigate its mechanism of action.Materials and MethodsThe potential plant metabolites and molecular targets of SHQXW in the context of pneumonia were determined through ultra-high performance liquid chromatography-tandem mass-spectrometry (UHPLC-MS/MS) and bioinformatics analysis. The therapeutic effect of SHQXW was evaluated in a KP-induced pneumonia murine model with imipenem/cilastatin as a positive control. Transcriptomics and non-targeted metabolomics were carried out to unveil potential mechanisms and targets for anti-pneumonia effects. Additionally, an in-depth exploration on the PI3K/AKT signaling pathway was conducted in this study.ResultsA total of 24 potential plant metabolites and 285 SHQXW-pneumonia-related targets selected by Homo sapiens were identified in this study. The tested doses of SHQXW significantly reduced mortality, improved body weight, decreased the lung index, reduced the bacterial load, and alleviated lung pathological damage in the KP-induced pneumonia murine model (p < 0.05). Notably, 1.3 g/kg/day of SHQXW provided the most effective protective outcome. Furthermore, SHQXW demonstrated the ability to suppress the production of inflammatory factors such as IL-1α, IL-1β, IL-3, IL-6, IL-12p70, G-CSF, GM-CSF, MCP-1, KC, and TNF-α. Analysis of transcriptomic and metabolomic data revealed that SHQXW could modulate inflammation-related signaling pathways (TNF, HIF-1, NF-κB, and PI3K/AKT) and metabolites to regulate pulmonary inflammation. Additional experiments using RT-qPCR and western blotting indicated that SHQXW may exert anti-inflammatory effects by activating the PI3K/AKT pathway.DiscussionThe findings indicate that SHQXW effectively reduces inflammation in mice with KP-induced pneumonia by modulating inflammatory signaling pathways and metabolites, rather than by directly inhibiting the growth of KP. This study introduces a novel treatment approach for KP-induced pneumonia and presents a new outlook on drug development.

Wind power generation has become an indispensable part of the power supply side of the power grid. Due to the intermittent and uncertain characteristics of wind energy, short-term wind power prediction plays an important role in the stable operation of power system. By constructing the digital twin model, real-time and high-precision prediction of wind energy is realized. First, the genetic algorithm-support vector machine (GA-SVM) algorithm is used to build the model. Multidimensional sensors and meteorological stations of the virtual wind power generation system collected the meteorological data of the environment and updated the meteorological history database at the same time. Second, based on the collected meteorological data, the preliminary prediction results are obtained, and by searching in the historical database, the predicted value and the actual output value of wind turbines or wind farms under similar conditions are obtained. Finally, the prediction results of the GA-SVM are modified to obtain the predicted value of the digital twin model. The prediction method can greatly improve the accuracy of the short-term forecast of wind energy.

Carbon monoxide (CO) is a gas that has no odor or color, making it difficult to detect until exposure leads to coma or death. CO poisoning is one of the most common and deadly poisonings around the world. CO poisoning is a common and often fatal form of poisoning worldwide. A toxic effect of CO is tissue hypoxia, which leads to systemic complications. Additionally, there may be severe neurological symptoms and delayed complications following CO poisoning. However, peripheral neuropathy is relatively rare after CO poisoning. Previously, only one case of unilateral plexopathy after CO poisoning, accompanied by rhabdomyolysis and cognitive dysfunction, has been reported. In this report, an isolated unilateral brachial plexopathy following CO intoxication is described. A key mechanism in this case may be CO-induced spinal cord ischemia. Immediate administration of hyperbaric oxygen therapy (HBOT) is crucial to prevent peripheral neuropathy after acute CO intoxication. Hyperbaric oxygen therapy (HBOT) should be administered immediately after acute CO intoxication to prevent peripheral neuropathy. Additionally, peripheral neuropathy following acute CO intoxication may benefit from consistent rehabilitation training.

The microbiota, also referred to as the microbial community, is a crucial component of the human microenvironment. It is located predominantly in various organs, including the intestines, skin, oral cavity, respiratory tract, and reproductive tract. The microbiota maintains a symbiotic relationship with the human body, influencing physiological and pathological functions to a significant degree. There is increasing evidence linking the microbial flora to human cancers. In contrast to the traditional belief that the urethra and urine of normal individuals are sterile, recent advancements in high-throughput sequencing technology and bacterial cultivation methods have led to the discovery of specific microbial communities in the urethras of healthy individuals. Given the prevalence of bladder cancer (BCa) as a common malignancy of the urinary system, researchers have shifted their focus to exploring the connection between disease development and the unique microbial community within tumors. This shift has led to a deeper investigation into the role of microbiota in the onset, progression, metastasis, prognosis, and potential for early detection of BCa. This article reviews the existing research on the microbiota within BCa tumors and summarizes the findings regarding the roles of different microbes in various aspects of this disease.

Background: Everolimus is an inhibitor of the mammalian target of rapamycin and is used to treat various tumors. The presented study aimed to evaluate the Everolimus-associated adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS).Methods: The AE records were selected by searching the FDA Adverse Event Reporting System database from the first quarter of 2009 to the first quarter of 2022. Potential adverse event signals were mined using the disproportionality analysis, including reporting odds ratio the proportional reporting ratio the Bayesian confidence propagation neural network and the empirical Bayes geometric mean and MedDRA was used to systematically classify the results.Results: A total of 24,575 AE reports of Everolimus were obtained using data from the FAERS database, and Everolimus-induced AEs occurrence targeted 24 system organ classes after conforming to the four algorithms simultaneously. The common significant SOCs were identified, included benign, malignant and unspecified neoplasms, reproductive system and breast disorders, etc. The significant AEs were then mapped to preferred terms such as stomatitis, pneumonitis and impaired insulin secretion, which have emerged in the study usually reported in patients with Everolimus. Of note, unexpected significant AEs, including biliary ischaemia, angiofibroma, and tuberous sclerosis complex were uncovered in the label.Conclusion: This study provided novel insights into the monitoring, surveillance, and management of adverse drug reaction associated with Everolimus. The outcome of serious adverse events and the corresponding detection signals, as well as the unexpected significant adverse events signals are worthy of attention in order to improving clinical medication safety during treatment of Everolimus.

Age-related cognitive impairment represents a significant health concern, with the understanding of its underlying mechanisms and potential interventions being of paramount importance. This study aimed to investigate the effects of hyperbaric oxygen therapy (HBOT) on cognitive function and neuronal integrity in aged (22-month-old) C57BL/6 mice. Male mice were exposed to HBOT for 2 weeks, and spatial learning and memory abilities were assessed using the Morris water maze. We employed transcriptome sequencing and Gene Ontology (GO) term enrichment analysis to examine the effects of HBOT on gene expression profiles, with particular attention given to synapse-related genes. Our data indicated a significant upregulation of postsynapse organization, synapse organization, and axonogenesis GO terms, likely contributing to improved cognitive performance. Moreover, the hyperphosphorylation of tau, a hallmark of many neurodegenerative diseases, was significantly reduced in the HBO-treated group, both in vivo and in vitro. Transmission electron microscopy revealed significant ultrastructural alterations in the hippocampus of the HBOT group, including an increase in the number of synapses and the size of the active zone, a reduction in demyelinated lesions, and a decreased number of “PANTHOS.” Furthermore, Western blot analyses confirmed the upregulation of PSD95, BDNF, and Syn proteins, suggesting enhanced synaptic plasticity and neurotrophic support. Moreover, HBOT increased autophagy, as evidenced by the elevated levels of Beclin-1 and LC3 proteins and the reduced level of p62 protein. Finally, we demonstrated that HBOT activated the AMPK-mTOR signaling pathway, a critical regulator of autophagy. Notably, our findings provide novel insights into the mechanisms by which HBOT ameliorates age-related cognitive impairment, suggesting the potential therapeutic value of this approach.

ObjectiveTo determine whether there is a causal relationship between thyroid dysfunction and the risk of age-related cataract (ARC) in the European population.DesignA two-sample Mendelian randomization (MR) study.MethodsHypothyroidism, hyperthyroidism, free thyroxine (fT4), and thyrotropin (TSH) were selected as exposures. The single nucleotide polymorphisms (SNP) of hypothyroidism and hyperthyroidism were obtained from the genome-wide association studies (GWAS) of the IEU database, including 337,159 subjects. Data for fT4 and TSH (72,167 subjects) were extracted from the ThyroidOmics Consortium. ARC was used as the outcome. The SNPs associated with ARC were selected from a GWAS of 216,362 individuals in the FinnGen database. The main method used was the inverse variance-weighted method, together with four complementary methods. Sensitivity analyses were performed using Cochran’s Q test, MR-PRESSO, MR-Egger regression and leave-one-out test. MR pleiotropy was used to test for pleiotropy. MR Steiger test was used to test for the directionality.ResultsTwo-sample MR analysis revealed a positive association between genetically predicted hypothyroidism and risk of ARC (OR = 2.501, 95% CI: 1.325-4.720; P = 0.004). Hyperthyroidism, circulating fT4 and TSH levels did not have a significant causal effect on ARC (P > 0.05). The results were robust and reliable, and no horizontal pleiotropy was found after sensitivity analyses. In the MR Steiger test, we found no reverse causal effects of hypothyroidism on the ARC (P

Stiff person syndrome (SPS) is a rare central nervous system disorder associated with malignancies. In this review, we retrieved information from PubMed, up until August 2023, using various search terms and their combinations, including SPS, stiff person syndrome spectrum disorders (SPSSDs), paraneoplastic, cancer, and malignant tumor. Data from peer-reviewed journals printed in English were organized to explain the possible relationships between different carcinomas and SPSSD subtypes, as well as related autoantigens. From literature searching, it was revealed that breast cancer was the most prevalent carcinoma linked to SPSSDs, followed by lung cancer and lymphoma. Furthermore, classic SPS was the most common SPSSD subtype, followed by stiff limb syndrome and progressive encephalomyelitis with rigidity and myoclonus. GAD65 was the most common autoantigen in patients with cancer and SPSSDs, followed by amphiphysin and GlyR. Patients with cancer subtypes might have multiple SPSSD subtypes, and conversely, patients with SPSSD subtypes might have multiple carcinoma subtypes. The first aim of this review was to highlight the complex nature of the relationships among cancers, autoantigens, and SPSSDs as new information in this field continues to be generated globally. The adoption of an open-minded approach to updating information on new cancer subtypes, autoantigens, and SPSSDs is recommended to renew our database. The second aim of this review was to discuss SPS animal models, which will help us to understand the mechanisms underlying the pathogenesis of SPS. In future, elucidating the relationship among cancers, autoantigens, and SPSSDs is critical for the early prediction of cancer and discovery of new therapeutic modalities.

IntroductionChronic musculoskeletal pain bothers the quality of life for approximately 1.71 billion people worldwide. Although pharmacological therapies play an important role in controlling chronic pain, overuse of opioids, persistent or recurrent symptoms, and pain-related disability burden still need to be addressed. Heat-stone massage is using the heated stone to stimulate muscles and ligaments followed by massage for relax, which can potentially treat the chronic musculoskeletal pain. To determine the efficacy and safety of heat-stone massage for patients with chronic musculoskeletal pain is needed.Methods and analysisThis multicenter, 2-arm, randomized, positive drug-controlled trial will include a total of 120 patients with chronic musculoskeletal pain. The intervention group will receive a 2 week heat-stone massage, 3 times per week, whereas the control group will receive the flurbiprofen plaster twice per day for 2 weeks. The primary end point is the change in Global Pain Scale from baseline to the end of the 2 week intervention. The secondary outcomes include the pain severity (Numerical Rating Scale), pain acceptance (Chronic Pain Acceptance Questionnaire), self-management (Health Education Impact Questionnaire), self-efficacy (Pain Self-Efficacy Questionnaire), anxiety and depression (Hospital Anxiety and Depression Scale), quality of life (Short Form-36). The intention-to-treat dataset will be used for analysis.DiscussionThe pain management remains the research topic that patients always pay close attention to. This will be the first randomized clinical trial to evaluate whether heat-stone massage, a non-pharmacological therapy, is effective in the chronic musculoskeletal pain management. The results will provide evidence for new option of daily practice.Clinical trial registrationWorld Health Organization Chinese Clinical Trial Registry [ChiCTR2200065654; https://www.chictr.org.cn/showproj.html?proj=185403]; International Traditional Medicine Clinical Trial Registry [ITMCTR2022000104; http://itmctr.ccebtcm.org.cn/en-US/Home/ProjectView?pid=51776b6f-77b8-4811-9b5a-a0fec10f2cee].

X-linked retinoschisis is more common in male children and rare in females. Clinically, male patients mainly present with early onset visual impairment or vision loss, and retinal retinoschisis due to division of the inner retina. We report a long-term observation of a female patient with familial foveal retinoschisis (FFR) caused by CRB1 gene with complex heterozygotic mutation. The initial symptoms of the female patient reported in this study were very similar to some early manifestations of X-linked retinoschisis (XLRS) caused by RS1 mutations involving macular fovea. However, as time going on, the splitting height at retinal fovea of FFR gradually decreased, and the splitting extent at retinal fovea of FFR gradually decreased.

Alzheimer’s disease (AD) is the most common chronic neurodegenerative disease worldwide. It causes cognitive dysfunction, such as aphasia and agnosia, and mental symptoms, such as behavioral abnormalities; all of which place a significant psychological and economic burden on the patients’ families. No specific drugs are currently available for the treatment of AD, and the current drugs for AD only delay disease onset and progression. The pathophysiological basis of AD involves abnormal deposition of beta-amyloid protein (Aβ), abnormal tau protein phosphorylation, decreased activity of acetylcholine content, glutamate toxicity, autophagy, inflammatory reactions, mitochondria-targeting, and multi-targets. The US Food and Drug Administration (FDA) has approved five drugs for clinical use: tacrine, donepezil, carbalatine, galantamine, memantine, and lecanemab. We have focused on the newer drugs that have undergone clinical trials, most of which have not been successful as a result of excessive clinical side effects or poor efficacy. Although aducanumab received rapid approval from the FDA on 7 June 2021, its long-term safety and tolerability require further monitoring and confirmation. In this literature review, we aimed to explore the possible pathophysiological mechanisms underlying the occurrence and development of AD. We focused on anti-Aβ and anti-tau drugs, mitochondria-targeting and multi-targets, commercially available drugs, bottlenecks encountered in drug development, and the possible targets and therapeutic strategies for future drug development. We hope to present new concepts and methods for future drug therapies for AD.

ObjectiveThe study aimed to explore the safety and effectiveness of percutaneous lordoplasty (PLP) in the treatment of severe osteoporotic vertebral compression fracture (OVCF).MethodsIncluded in this prospective study were patients with single-segment acute severe OVCF who were treated with PLP in our institution from July 2016 to October 2019. Patients' back pain and quality of life were assessed using the visual analog scale (VAS) and SF-36 scores. Lateral X-ray radiography of the spine was performed to measure the vertebral height, vertebral kyphotic angle, and segmental kyphotic angle, and to evaluate the outcome of fracture reduction and kyphotic correction. Intra-and postoperative complications were recorded.ResultsOf the 51 included patients, 47 patients were followed up for 12 months. The VAS score decreased from preoperative 7.33 ± 1.92 to postoperative 1.76 ± 0.85 at the 12th month (p < 0.05), and the SF-36 score increased from preoperative 79.50 ± 9.22 to postoperative 136.94 ± 6.39 at the 12th month (p < 0.05). During the 1-year follow-up period, the anterior height of the vertebral body increased significantly from preoperative 10.49 ± 1.93 mm to 19.33 ± 1.86 mm (p < 0.05); the posterior height of the vertebral body increased insignificantly from preoperative 22.23 ± 2.36 mm to 23.05 ± 1.86 mm (p > 0.05); the vertebral kyphotic angle decreased significantly from preoperative 18.33° ± 11.49° to 8.73° ± 1.21° (p < 0.05); and the segmental kyphotic angle decreased significantly from preoperative 24.48° ± 4.64° to 11.70° ± 1.34° (p < 0.05). During the 1-year follow-up period, there was no significant difference in the radiologic parameters, VAS scores, and SF-36 scores, between the 1st day and the 12th month of post-operation (P > 0.05). No nerve damage occurred in any of the cases. Intraoperative cement leakage occurred in six cases, and the fracture of the adjacent vertebral body occurred in one case.ConclusionPLP can well reduce the risk of fracture and achieve good kyphotic correction and may prove to be a safe, cost-effective and minimally invasive alternative option for the treatment of severe OVCF with kyphotic deformity.

IntroductionCochlear implantation is currently the most successful intervention for severe-to-profound sensorineural hearing loss, particularly in deaf infants and children. Nonetheless, there remains a significant degree of variability in the outcomes of CI post-implantation. The purpose of this study was to understand the cortical correlates of the variability in speech outcomes with a cochlear implant in pre-lingually deaf children using functional near-infrared spectroscopy (fNIRS), an emerging brain-imaging technique.MethodsIn this experiment, cortical activities when processing visual speech and two levels of auditory speech, including auditory speech in quiet and in noise with signal-to-noise ratios of 10 dB, were examined in 38 CI recipients with pre-lingual deafness and 36 normally hearing children whose age and sex matched CI users. The HOPE corpus (a corpus of Mandarin sentences) was used to generate speech stimuli. The regions of interest (ROIs) for the fNIRS measurements were fronto-temporal-parietal networks involved in language processing, including bilateral superior temporal gyrus, left inferior frontal gyrus, and bilateral inferior parietal lobes.ResultsThe fNIRS results confirmed and extended findings previously reported in the neuroimaging literature. Firstly, cortical responses of superior temporal gyrus to both auditory and visual speech in CI users were directly correlated to auditory speech perception scores, with the strongest positive association between the levels of cross-modal reorganization and CI outcome. Secondly, compared to NH controls, CI users, particularly those with good speech perception, showed larger cortical activation in the left inferior frontal gyrus in response to all speech stimuli used in the experiment.DiscussionIn conclusion, cross-modal activation to visual speech in the auditory cortex of pre-lingually deaf CI children may be at least one of the neural bases of highly variable CI performance due to its beneficial effects for speech understanding, thus supporting the prediction and assessment of CI outcomes in clinic. Additionally, cortical activation of the left inferior frontal gyrus may be a cortical marker for effortful listening.

Compared with quartz sand, recycled aggregate sand is characterized by the high liquefaction and shear resistance because of its irregular particle shape. However, the interrelationship between its particle shape and shear behaviors is seldom investigated. This paper investigates the role of the particle shape on the shear behaviors of recycled aggregate sand by conducting a series of monotonic and cyclic simple shear tests under undrained constant volume conditions. The particles’ morphology parameters are assessed in terms of sphericity, roundness and regularity with microscopic observation and image processing. According to the experimental results, the recycled aggregate sand with irregular shapes mobilizes greater gradients of the flow liquefaction lines under monotonic shear conditions. The irregularity of the particle shape also leads to greater peak shear stress and dynamic shear modulus, indicating stronger shear and liquefaction resistances under the cyclic shearing. Furthermore, the interrelationships between the peak shear stress, dynamic shear modulus and particle shape of the samples are revealed and established by well fitted functions, which could serve as references for the selection of recycled aggregate sand and corresponding designs of the foundation.

BackgroundExtramedullary plasmacytoma (EMP) is a localized plasma cell neoplasm that originates from tissues other than bone. The survival trends and prognostic factors of patients with EMP in recent years remain unreported.MethodsWe used the SEER databases to extract the data. Survival curves were calculated using the Kaplan-Meier method and a nomogram was created based on the Cox’s proportional hazards model.ResultsA total of 1676 cases of EMP were identified. Patients in period-2 (2008-2016) show similar survival (p=0.8624) to those in period-1(1975-2007). Age, gender, race, and sites were prognostic of patient outcomes. And the use of surgery was associated with improved survival. The patients were randomly assigned to the training cohort and the validation cohort in a ratio of 2:1. Four factors including age, gender, race, and sites were identified to be independently predictive of the overall survival of patients with EMP. A prognostic model (EMP prognostic index, EMP-PI) comprising these four factors was constructed. Within the training cohort, three risk groups displayed significantly different 10-year survival rates: low-risk (73.0%, [95%CI 66.9-78.2]), intermediate-risk (39.3%, [95%CI 34.3-44.3]), and high-risk (22.6%, [95%CI 15.3-30.9]) (p

Urolithin A (UA) has received considerable research attention because of its health benefits. However, only a few strains have been reported to produce UA from ellagic acid (EA), and the molecular mechanisms underlying the gut microbiota-mediated transformation of ellagic acid into urolithin A is limited. In the present study, a single strain FUA027 capable of converting ellagic acid into UA in vitro was isolated from the fecal samples. The strain was identified as Enterococcus faecium through the morphological, physiological, biochemical and genetic tests. UA was produced at the beginning of the stationary phase and its levels peaked at 50 h, with the highest concentration being 10.80 μM. The strain Enterococcus faecium FUA027 is the first isolated strain of Enterococcus sp. producing urolithin A from ellagic acid, which may be developed as probiotics and used to explore molecular mechanisms underlying the biotransformation of ellagic acid into UA.

Photoperiod responsiveness is important to soybean production potential and adaptation to local environments. Varieties from temperate regions generally mature early and exhibit extremely low yield when grown under inductive short-day (SD) conditions. The long-juvenile (LJ) trait is essentially a reduction and has been introduced into soybean cultivars to improve yield in tropical environments. In this study, we used next-generation sequencing (NGS)-based bulked segregant analysis (BSA) to simultaneously map qualitative genes controlling the LJ trait in soybean. We identified two genomic regions on scaffold_32 and chromosome 18 harboring loci LJ32 and LJ18, respectively. Further, we identified LJ32 on the 228.7-kb scaffold_32 as the soybean pseudo-response-regulator gene Tof11 and LJ18 on a 301-kb region of chromosome 18 as a novel PROTEIN FLOWERING LOCUS T-RELATED gene, Glyma.18G298800. Natural variants of both genes contribute to LJ trait regulation in tropical regions. The molecular identification and functional characterization of Tof11 and LJ18 will enhance understanding of the molecular mechanisms underlying the LJ trait and provide useful genetic resources for soybean molecular breeding in tropical regions.

High-fat diets (HFDs) are related to the incidence of obesity and diabetes, but the effect of high-fat diet-induced brain damage remains to be clarified. In our study, we found that 24 weeks of a HFD effectively induced obesity and a change in fur color in mice. In addition, the mice also exhibited deficits in learning and memory. We further found that autophagic flux was impaired in mice after HFD feeding. Hypoxia-inducible factor 1α (HIF-1α) expression was significantly increased in HFD-fed mice, and HFD feeding inhibited adenosine monophosphate-activated protein kinase (AMPK) phosphorylation and induced mechanistic target of rapamycin (mTOR) phosphorylation and p70S6K expression. Treatment of HFD-induced BV2 cell model with palmitic acid (PA) was used to further verify a similar result. We concluded that improving tissue hypoxia or enhancing autophagy through the AMPK/mTOR/p70S6K pathway may be a relevant strategy for improving obesity- and ageing-related disorders.

Objective: The purpose of this study was to analyze the stability and instrument-related complications associated with fixation of the lumbar spine using the Short-Rod (SR) technique.Methods: Using finite element analysis, this study assessed the stability of a bilateral lumbar fixation system when inserting the pedicle screws at angles of 10°, 15°, and 20° to the endplate in the sagittal plane. Using the most stable construct with a screw angle, the model was then assessed with different rod lengths of 25, 30, 35, and 45 mm. The optimal screw inclination angle and rod length were incorporated into the SR model and compared against traditional parallel screw insertion (pedicle screws in parallel to the endplate, PPS) in terms of the stability and risk of instrument-related complications. The following parameters were evaluated using the validated L4–L5 lumbar finite element model: axial stiffness, range of motion (ROM), stress on the endplate and facet joint, von-Mises stress on the contact surface between the screw and rod (CSSR), and screw displacement.Results: The results showed that the SR model with a 15° screw inclination angle and 35 mm rod length was superior in terms of construct stability and risk of complications. Compared to the PPS model, the SR model had lower stiffness, lower ROM, less screw displacement, and lower stress on the facet cartilage, the CSSR, and screws. However, the SR model also suffered more stress on the endplate in flexion and lateral bending.Conclusion: The SR technique with a 15° screw inclination and 35 mm rod length offers good lumbar stability with a low risk of instrument-related complications.

Objectives: To examine associations between maternal sulfur dioxide (SO2) exposure and congenital ear malformations risk in offspring.Methods: We surveyed 1676 cases with congenital ear malformations and 7950 controls from the Maternal and Child Health Certificate Registry of Liaoning Province between 2010 and 2015. SO2 concentrations were obtained from the Municipal Environment Protection Bureau of Liaoning Province. Multivariable logistic regression models and Restricted cubic splines (RCS) model were used to assess the aforementioned association.Results: There were significant associations between maternal SO2 exposure and congenital ear malformations risk during the 3 months before conception (OR Q4 vs. Q1 = 1.93, 95% CI = 1.43–2.59) and the 3 months after conception (OR Q4 vs. Q1 = 1.63, 95% CI = 1.22–2.18). Similar results were obtained in the analysis of single-month exposure windows, except for the third month before conception and the third month after conception. Moreover, these findings were broadly consistent across subgroups and robust in sensitivity analyses. There were non-linear dose-response associations between SO2 exposure and congenital ear malformations based on restricted cubic spline model analysis.Conclusion: Maternal SO2 exposure is associated with increased congenital ear malformations risk in offspring.

The prediction of photovoltaic power generation is helpful to the overall allocation of power planning departments and improves the utilization rate of photovoltaic power generation. Therefore, this study puts forward an ultra-short-term power forecasting model of a photovoltaic power station based on modal decomposition and deep learning. The methodology involved taking the data of a 50 MW photovoltaic power generation system in the Inner Mongolia Autonomous Region as a sample. Furthermore, the weather conditions were classified, and the historical power data were decomposed into multiple VMF subcomponents and residual terms by the VMD method. Then, the residual term was decomposed twice by the CEEMDAN method. All subcomponents were sent to the LSTM network for prediction, and the predicted value of the photovoltaic power station was obtained by superimposing the subcomponent prediction results. ARIMA, SVM, LSTM, and VMD-LSTM models were built to compare the accuracy with the proposed models. The results revealed that the prediction accuracy of a non-combination forecasting model was limited when the weather suddenly changed. The VMD method was used to decompose the residual term twice, which could fully extract the complex data information in the residual term, and when compared with the VMD-LSTM model, the eRMSE, eMAPE, and eTIC of the VMD-CEEMDAN-LSTM model were reduced by 0.104, 16.596, and 0.038, respectively. The second decomposition technology has obvious prediction advantages. The proposed quadratic modal decomposition model effectively improves the precision of ultra-short-term prediction of photovoltaic power plants.

The diet of prehistoric humans in the Qijia period (4,400–3,500 BP) was significantly changed by the advent of dry agriculture and food globalization. However, it is yet to be proven whether wild plants were exploited despite the cultivation of millet, and whether wheat crops, cattle, and sheep originating from southwestern Asia were adopted into the regional human diet. This study presents stable isotope, starch grain, and phytolith analyses of 24 human teeth from the Lajia site in Qinghai, which is a representative Qijia culture settlement site. The carbon and nitrogen isotope results show that the subjects primarily ate C4 plants and had a high protein diet. Starch grain and phytolith results showed that the inhabitants consumed broomcorn millet (Panicum miliaceum), foxtail millet (Setaria italica), Triticeae, tubers and roots, along with other Pooideae and Poaceae plants. This data proves that although broomcorn and foxtail millet formed the mainstay of the Qijia diet, it also included a wide range of plants, such as the tribe Triticeae, tubers and roots, which would have been foraged rather than grown. Compared with the other three contemporaneous sites in Northern China, the proportion of millet starches was highest at the Lajia site, while the type and proportion of foraged plants were the lowest. This was probably because of the arid environment in the region, which could not have supported sufficient plant resources for foraging, which in turn might have led to enhanced millet cultivation and/or a greater reliance on hunting. No wheat or barley traces were found in human teeth in Lajia, and the high proportion of nitrogen was possibly related to the consumption of sheep because sheep bones were found in a zooarchaeological study. This study enhances our understanding of the subsistence strategies present in Qijia culture and of prehistoric food globalization, which is of pivotal significance for a deeper understanding of interactions between east and west Asia during the Neolithic and Bronze ages.

With the access to a large number of intermittent and fluctuating new energy sources in the low-voltage distribution network, the complex relationship between producers and consumers makes the node voltage stability and other problems in the power system increasingly prominent. Aiming at the voltage stability problem caused by the intermittent and fluctuation of the new power system, based on the high-precision measurement data of PMU, this article used the model predictive control algorithm to realize regional voltage optimization and improve the stability of node voltage. First, the voltage sensitivity matrix is calculated using PMU measurement data and grid structure state information. Second, active power, reactive power, and voltage were taken as the input of the MPC algorithm, and the optimal compensation voltage instruction was obtained by rolling optimization, and the node voltage was compensated by SVG and SVC. Finally, a simulation experiment was carried out on the MATLAB/Simulink simulation platform, and the experimental results verified the correctness and effectiveness of the proposed control method.

Evidence of the association between maternal sulfur dioxide (SO2) exposure and the risk of omphalocele is limited and equivocal. We aimed to assess the aforementioned topic during the first trimester of pregnancy. A population-based case-control study was carried out in infants consisting of 292 cases of omphalocele and 7,950 healthy infant controls. Exposure to SO2, particulate matter with aerodynamic diameters ≤ 10 μm, and nitrogen dioxide was assessed by averaging the concentration from all stations in the mother's residential city. SO2 exposure was categorized into three groups, with the lowest tertile defined as the reference category. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using multivariable logistic regression models. Higher SO2 exposure during the first trimester was significantly associated with omphalocele risk [per standard deviation (42 ug/m3) increment: OR = 1.39, 95% CI = 1.22–1.65]. When focusing on shorter exposure windows, similar positive associations were observed for SO2 exposure in the first and third months of pregnancy. In addition, compared with the lowest tertile, high SO2 exposure in the second month of pregnancy increased the risk of omphalocele (OR = 2.80, 95% CI = 1.61–4.97). Maternal exposure to SO2 during the first trimester may increase the risk of omphalocele in offspring.

In undertaking a functional study of ceramic Li tripods, a common archaeological artifact in Northeast China during the Bronze Age, this study provides a crucial insight into both the function of these ceramics, plant resource strategies and human diets during this period. The precise function of the Li tripod has to date been controversial due to a lack of direct contextual evidence. Hence, this paper presents analyses of 10 Li tripods from six sites in the Chifeng area of Northeast China, all of which can be dated from their excavation contexts to the Lower Xiajiadian cultural period (3,900–3,400 cal a B.P.). The interior and exterior surfaces of the tripods were analyzed using starch grain analysis, phytolith analysis and microfossil charcoal analysis. A total of 133 starch grains were recovered, of which 111 (83.46%) were found on 80% of the interior surfaces examined. Further analysis found that these starch grains had damage features specifically gelatinised characteristics, which were consistent with the starch grains that had been boiled in our cooking simulations. In addition, there were obvious soot traces on the surfaces of the tripods, 2,835 microfossil charcoal grains not completely burned were identified, and 70% of the exterior surface samples had a higher frequency of contact with fire. These findings serve to confirm that Li tripods were used in the cooking of food. Of the 133 starch grains found, only 62 could be identified to species level. These were foxtail millet (Setaria italica) and broomcorn millet (Panicum milliaceum) and plants from Triticeae taxa, as well as roots and tubers. The 3,424 phytoliths recovered from the 10 tripods were found to belong to the Panicoideae and Pooideae genera, of which the husks from foxtail and broomcorn millets from the Panicoideae genus accounted for 6.19% of the total. These results indicate that millets, the Triticeae, roots, and tubers, in addition to plants from Panicoideae and Pooideae genera, were utilized in the Chifeng area of Northeast China during the Bronze Age. This study deepens our understanding of the local subsistence patterns and the social context of early Bronze age civilization in the region.

To solve the instability problem of wind turbine power output, the wind power was predicted, and a wind power prediction algorithm optimized by the backpropagation neural network based on the CSO (cat swarm optimization) algorithm was studied, and a wind farm energy storage system model was built on this basis. By collecting the wind power plant’s historical wind speed, power, and other parameters, the short-term wind farm output power was predicted, and the operation of the wind farm energy storage system was controlled to suppress the output power of the wind farm when the wind farm was connected to the grid so as to improve the stability of the output power of the wind farm. At the same time, typical wind farm data were taken as an example to verify the feasibility of the proposed method.

BackgroundSevere hyperlipidemia is characterized by markedly elevated blood triglyceride levels and severe early-onset cardiovascular diseases, pancreatitis, pancreatic necrosis or persistent multiple organ failure if left untreated. It is a rare autosomal recessive metabolic disorder originated from the variants of lipoprotein lipase gene, and previous studies have demonstrated that most cases with severe hyperlipidemia are closely related to the variants of some key genes for lipolysis, such as LPL, APOC2, APOA5, LMF1, and GPIHBP1. Meanwhile, other unidentified causes also exist and are equally worthy of attention.MethodsThe 29-day-old infant was diagnosed with severe hyperlipidemia, registering a plasma triglyceride level as high as 25.46 mmol/L. Whole exome sequencing was conducted to explore the possible pathogenic gene variants for this patient.ResultsThe infant was put on a low-fat diet combined with pharmacological therapy, which was successful in restraining the level of serum triglyceride and total cholesterol to a low to medium range during the follow-ups. The patient was found to be a rare novel homozygous duplication variant-c.45_48dupGCGG (Pro17Alafs*22) in GPIHBP1 gene-leading to a frameshift which failed to form the canonical termination codon TGA. The mutant messenger RNA should presumably produce a peptide consisting of 16 amino acids at the N-terminus, with 21 novel amino acids on the heels of the wild-type protein.ConclusionsOur study expands on the spectrum of GPIHBP1 variants and contributes to a more comprehensive understanding of the genetic diagnosis, genetic counseling, and multimodality therapy of families with severe hyperlipidemia. Our experience gained in this study is also contributory to a deeper insight into severe hyperlipidemia and highlights the importance of molecular genetic tests.

Individual variations in concentrations of rituximab in different B cell non-Hodgkin’s lymphoma subtypes and their relevance to efficacy were still unclear. From 2016 to 2021, a prospective clinical trial was conducted, and 510 samples with 6 uncommon subtypes of B-cell lymphoma were enrolled to examine the pharmacokinetic behaviour of rituximab and its impact on clinical outcomes, including complete response (CR), progression-free survival (PFS) and overall survival (OS). Considerable variability was observed in the rituximab trough concentration in the first cycle (C1-trough, 1.16–55.52 μg/ml) in patients with different lymphoma subtypes. Patients with “double-hit” lymphoma (4.01 ± 0.77 μg/ml) or mantle cell lymphoma (MCL; 15.65 ± 16.45 μg/ml) had much lower C1-trough and worse outcomes. Great individual variation in the C1-trough existed among patients with mucosa-associated lymphoma (MALT), and the high C1-trough observed in patients treated with the RB regimen was associated with a better response than was obtained with R-CHOP (38.41 ± 14.13 μg/ml vs 15.49 ± 8.80 μg/ml, p = 0.0029). Despite the high aggressiveness of the cancer, Burkitt lymphoma patients receiving intensive chemotherapy had the highest C1-trough (28.85 ± 9.35 μg/ml) and maintained long-term PFS. The C1-trough in patients with mixed, unclassifiable B-cell lymphoma was close to 20 μg/ml, and these patients had acceptable outcomes. Overall, a low rituximab C1-trough was associated with adverse consequences, including persistent progression, early recurrence and a short OS, however, some high-risk factors appeared to be balanced by the presence of a high C1-trough. Basal levels of circulating CD19+ lymphocytes differed between and within patients with diverse lymphoma subtypes and were negatively correlated with C1-trough. Therefore, the traditional doses of rituximab are inadequate for patients with “double-hit” lymphoma and MCL. Increasing the initial rituximab dose according to the disease, high-risk factors and even the baseline CD19+ lymphocyte count will be new methods to optimize therapeutic regimens for patients with different lymphoma subtypes.

Aim: This study analyzes the effects of retrospective stressful life events on current depression among Chinese older people and how these effects are moderated by social support. Stressful life events comprise bereavement, divorce, health adversities, accidents, and financial losses due to fraud.Data and Method: Data were drawn from the China Health and Retirement Longitudinal Study (CHARLS) of the 2015 panel, and responses from 9,619 older people aged over 60 years were used. The least-squares regression method was applied to measure the linear effects. Propensity score matching minimized selection bias and enabled the measurement of the net effects of stressful life events. The bias-corrected matching estimator was also used to correct the inexact matching bias from propensity score matching.Result: Experienced stressful life events and exposure to cumulative stressful life events were found to lead to depression in older people. When older people experienced stressful life events but with more social activities, and higher satisfaction and frequent contact with children, their depressive levels were lower. The results of the propensity score matching showed that stressful life events resulted in depression in older people. Furthermore, individuals with family support were able to moderate stressful life events effects; however, the moderating effects of social activity separately were negligible. In sum, with the moderating role of family support and social activity, the average differences in older people depression caused by stressful life events decreased.Conclusion: Experiencing stressful life events is detrimental to the psychological health of the older people. Social support, including family support and social activity, has buffered detrimental effects on depression caused by stressful life events.Interpretations: The study underscores the need to supply effective interventions for the older people who experienced stressful life events. First, society should improve the capability of community care centers to supply mental health services. Second, family members should pay attention to mental condition of older people, and specific support should concord with the needs of Chinese older people. In addition, support suppliers can move from being confined to kinship relationships to close relationships, such as the community partners and neighbors.

Mastitis is one of the most serious diseases that causes losses in the dairy industry, seriously impairing milk production and milk quality, and even affecting human health. Menthol is a cyclic monoterpene compound obtained from the stem and leaves of peppermint, which has a variety of biological activities, including anti-inflammatory and antioxidant activity. The purpose of this study was to investigate the preventive effect of menthol on the lipopolysaccharide-induced inflammatory response in primary bovine mammary gland epithelial cells (BMECs) and its anti-inflammatory mechanism. First, BMECs were isolated and amplified from the udders of Holstein cows by enzymatic hydrolysis. BMECs were treated with menthol (10, 50, 100, 200 μM) for 1h, followed by lipopolysaccharide (5μg/ml) for 12 h. Lipopolysaccharide treatment upregulated the protein levels of cyclooxygenase-2 (COX-2) and inducible nitric oxide synthase (INOS) and the mRNA abundance of tumor necrosis factor α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β), while menthol was able to inhibit this effect. The inhibitory effect of menthol on proinflammatory factors was significantly reduced when autophagy was blocked using 3-Methyladenine (5μg/ml), an inhibitor of autophagy. Furthermore, lipopolysaccharide treatment reduced the expression levels of milk lipids and milk proteins, which were inhibited by menthol. In addition, menthol (200 μM) treatment was able to significantly upregulate the expression level of autophagy-related protein LC3B, downregulate the expression level of P62, promote the expression abundance of autophagy-related gene mRNA, and enhance significantly enhance autophagic flux. Interestingly, treatment of BMECs with menthol (200 μM) promoted the phosphorylation of AMP-activated protein kinase (AMPK) and unc-51 like kinase 1 (ULK1) and increased the nuclear localization of nuclear factor-E2 associated factor 2 (Nrf-2). When the AMPK pathway was blocked using compound C (10μg/ml), an inhibitor of AMPK, autophagy was significantly inhibited. Autophagy levels were significantly decreased after blocking the Nrf-2 pathway using ML385 (5μg/ml), an inhibitor of Nrf-2. Overall, the data suggest that menthol activates the AMPK-ULK1 pathway to initiate the onset of autophagy and maintains the level of autophagy through the AMPK-Nrf-2 pathway. In conclusion, the findings suggest that menthol may alleviate the inflammatory response in BMECs via the AMPK/ULK1/Nrf-2/autophagy pathway.

Background: Kidney transplantation (KTx) is a preeminent treatment for end-stage renal disease (ESRD). After the application of immunosuppressants (IS), renal allograft recipients could reach a state called accommodation which means they are neither rejected nor infected. This study aimed to describe the details of this immune accommodation and reveal a novel mechanism of IS on immune cell subpopulations.Methods: We analyzed multiple cell subgroups and their gene expression of peripheral T, B, myeloid, and NK cells from renal allograft recipients with accommodation and healthy control (HC) by single-cell transcriptomics sequencing (scRNA-seq) and flow cytometry.Results: A total of 8,272 cells were isolated and sequenced from three individuals, including 2,758 cells from HC, 2,550 cells from ESRD patient, and 2,964 cells from KTx patient, as well as 396 immune response–related genes were detected during sequencing. 5 T-cell, 4 NK-cell, 5 myeloid, and 4 B-cell clusters were defined. Among them, a B-cell subset (CD19+IGLC3lowIGKChighTCL1A-CD127+) of renal transplant recipients with accommodation was significantly lower than that of HC and verified by flow cytometry, and this B-cell subset showed an activated potential because of its high expression of CD127. Furthermore, we found that IL32 might be the key cytokine to induce the differentiation of this B-cell cluster.Conclusion: We found a novel B-cell subset (CD19+IGLC3lowIGKChighTCL1A-CD127+) which was inhibited and decreased in renal allograft recipients with accommodation. This study might reveal the effect of commonly used IS in clinical practice on B-cell subsets and related mechanism.

Prader–Willi syndrome (PWS) is a complex genetic syndrome caused by the loss of function of genes in 15q11-q13 that are subject to regulation by genomic imprinting and expressed from the paternal allele only. The main clinical features of PWS patients are hypotonia during the neonatal and infantile stages, accompanied by delayed neuropsychomotor development, hyperphagia, obesity, hypogonadism, short stature, small hands and feet, mental disabilities, and behavioral problems. However, PWS has a clinical overlap with other disorders, especially those with other gene variations or chromosomal imbalances but sharing part of the similar clinical manifestations with PWS, which are sometimes referred to as Prader–Willi syndrome-like (PWS-like) disorders. Furthermore, it is worth mentioning that significant obesity as a consequence of hyperphagia in PWS usually develops between the ages of 1 and 6 years, which makes early diagnosis difficult. Thus, PWS is often not clinically recognized in infants and, on the other hand, may be wrongly suspected in obese and intellectually disabled patients. Therefore, an accurate investigation is necessary to differentiate classical PWS from PWS-like phenotypes, which is imperative for further treatment. For PWS, it is usually sporadic, and very rare family history and affected siblings have been described. Here, we report the clinical and molecular findings in a three-generation family with a novel 550-kb microdeletion affecting the chromosome 15 imprinting center (IC). Overall, the present study finds that the symptoms of our patient are somewhat different from those of typical PWS cases diagnosed and given treatment in our hospital. The familial occurrence and clinical features were challenging to our diagnostic strategy. The microdeletion included a region within the complex small nuclear ribonucleoprotein polypeptide protein N (SNRPN) gene locus encompassing the PWS IC and was identified by using a variety of techniques. Haplotype studies suggest that the IC microdeletion was vertically transmitted from an unaffected paternal grandmother to an unaffected father and then caused PWS in two sibling grandchildren when the IC microdeletion was inherited paternally. Based on the results of our study, preimplantation genetic diagnosis (PGD) was applied successfully to exclude imprinting deficiency in preimplantation embryos before transfer into the mother’s uterus. Our study may be especially instructive regarding accurate diagnosis, differential diagnosis, genetic counseling, and PGD for familial PWS patients.

AimPost-operative fatigue syndrome (POFS) is a common complication that prolongs the recovery to normal function and activity after surgery. The aim of the present study was to explore the mechanism of central fatigue in POFS and the anti-fatigue effect of ginsenoside Rb1.MethodWe investigated the association between inflammation, indoleamine 2,3-dioxygenase (IDO) enzyme, and tryptophan metabolism in the hippocampus of POFS rats. A POFS rat model was induced by major small intestinal resection. Rats with major small intestinal resection were administered ginsenoside Rb1 (15 mg/kg) once a day from 3 days before surgery to the day of sacrifice, or with saline as corresponding controls. Fatigue was assessed with the open field test (OFT) and sucrose preference test (SPT). ELISA, RT-PCR, Western blot, immunofluorescence, and high-performance liquid chromatography (HPLC) were used to test the inflammatory cytokines; p38MAPK, NF-κB/p65, and IDO enzyme expressions; and the concentrations of tryptophan, kynurenine, and serotonin, respectively.ResultOur results showed that POFS was associated with increased expressions of inflammatory cytokines and p38MAPK and higher concentrations of kynurenine and tryptophan on post-operative days 1 and 3; a lower serotonin level on post-operative day 1; and an enhanced translocation of NF-κB/p65 and the IDO enzyme on post-operative days 1, 3, and 5. Ginsenoside Rb1 had an improvement effect on these.ConclusionInflammatory cytokines induced by large abdominal surgery disturb tryptophan metabolism to cause POFS through the activation of the p38MAPK–NF-κB/p65–IDO pathway in the hippocampus. Ginsenoside Rb1 had an anti-fatigue effect on POFS by reducing inflammation and IDO enzyme.

Limited studies have focused on the impact of ambient air pollution on spina bifida. A population-based case-control study was conducted in Liaoning Province, China to assess the associations between maternal PM10 exposures in various exposure windows and spina bifida risk. Data on spina bifida cases born between 2010 and 2015 were available from the Maternal and Child Health Certificate Registry of Liaoning Province. Controls were a random sample of healthy livebirths without any birth defects delivered in the selected five cities during 2010–2015. Ambient air monitoring data for PM10 were obtained from 75 monitoring stations in Liaoning Province. The multivariable logistic regression models were established to calculate adjusted odds ratios (OR) and 95% confidence intervals (CI). We further performed sensitivity analyses by using three propensity score methods. A total of 749 spina bifida cases and 7,950 controls were included. After adjusting for potential confounders, spina bifida was associated with a 10 μg/m3 increment in PM10 during the first trimester of pregnancy (adjusted OR = 1.06, 95% CI: 1.00–1.12) and the 3 months before pregnancy (adjusted OR = 1.12, 95% CI: 1.06–1.19). The adjusted ORs in the final model for the highest vs. the lowest quartile were 1.51 (95% CI: 1.04–2.19) for PM10 during the first trimester of pregnancy and 2.01 (95% CI: 1.43–2.81) for PM10 during the 3 months before pregnancy. Positive associations were found between PM10 exposures during the single month exposure windows and spina bifida. Sensitivity analyses based on two propensity score methods largely reported similar positive associations. Our findings support the evidence that maternal PM10 exposure increases the risk of spina bifida in offspring. Further, validation with a prospective design and a more accurate exposure assessment is warranted.

NAP1L1 has been reported to be significantly involved in the carcinogenesis of hepatocellular carcinoma (HCC). Yet, its detailed molecular basis is still to be determined. Based on the analysis of The Cancer Genome Atlas (TCGA) database, NAP1L1 mRNA was found to be upregulated and predicted the poor prognosis initially. Subsequently, consistent with the prediction, the upregulated expression of NAP1L1 mRNA and protein levels was confirmed by quantitative polymerase chain reaction (qPCR), Western blot, and immunohistochemistry assays. Upregulated NAP1L1 protein positively promoted the disease progression and poor prognosis of HCC. In addition, NAP1L1 protein expression was considered as an independent prognostic factor in HCC. Inhibition of NAP1L1 expression by siRNA or shRNA pathway significantly reduced the cell proliferation and cell cycle transformation in vitro and in vivo. Mechanism analysis first showed that the function of NAP1L1 was to recruit hepatoma-derived growth factor (HDGF), an oncogene candidate widely documented in tumors. Furthermore, the latter interacted with c-Jun, a key oncogenic transcription factor that can induce the expression of cell cycle factors and thus stimulate the cell growth in HCC. Finally, transfecting HDGF or c-Jun could reverse the suppressive effects on HCC growth in NAP1L1-suppressed HCC cells. Our data indicate that NAP1L1 is a potential oncogene and acts via recruiting HDGF/c-Jun in HCC.

While China has decreasing female labor participation and increasing marital instability, compared to the rest of the world, its female labor participation rate is higher on average. The effect of female labor force status on couples' marital satisfaction, as one of the main factors for evaluating marital quality, has been separately discussed, including extensive margins considering whether women are in the labor market and intensive margins on women working hours per week. This study analyzed data from the 2014 China Family Panel Studies (CFPS) using a binary logit model and a stability test. Results showed that the work hours, rather than the occupational status, of women affect marital satisfaction. In addition, regardless of the gender role attitudes held by the couple, marital satisfaction increases when women are in the labor market. This study has retroactively reviewed the effects of women working outside the home on marital quality. The dual roles of Chinese women, as both employee and homemaker, have been socially accepted. However, the requirements of maintaining multiple roles often contradict and present conflicts among the roles, time, and pressure, in the long run, giving rise to marital dissatisfaction.

With the aim of achieving high precision and high efficiency, recent research on hydraulic flood models has tended to focus on the algorithms for solving the shallow water equations of Saint-Venant. While development of the algorithms will help to improve the simulation precision and the solving of specific problems, the other influential factor in flood risk modeling is the precision and reasonable generalization of the data. This is even more important for increasing the model’s computational accuracy and efficiency but is frequently undervalued. Frequent rainstorm waterlogging is having a serious impact on China’s large cities. Early warning of waterlogging risk following a rainstorm forecast is an effective method for preventing or reducing potential losses. Concrete waterlogging information including locations, depth, and process is essential for early warnings. This paper focuses on the influence of data precision and reasonable generalization on an urban flooding model. A detailed hydraulic urban flooding model characterized by detailed data processing and component coupling can help to provide advance information. In Beijing city, road networks, overpasses, and buildings are so highly concentrated that rainstorms easily result in waterlogging in low-lying locations. Therefore, partial microrelief is the determinate factor in waterlogging simulation. This paper shows that multi-mode surface data generalization and detailed model coupling support a perfect simulation of a Beijing urban flooding model. The influence of buildings, roads, and overpasses on surface water flow was carefully considered based on the innovative aspect of a fine generalization of partial microrelief. One novelty is the simulation of the whole overland flow from the beginning of rainfall to mesh, not only from manhole overflow, because the waterlogging is caused mainly by initial surface water runoff rather than by manhole overflow. A second novelty is the use of a new kind of coupling mode based on physical mechanisms between surface and pipe models. Here, rain perforated strainers instead of manholes play a role as flow exchange points between pipe and surface. This coupling mode is much closer to the real world. Based on a detailed Beijing urban flooding model, a scenarios library of typical rainfall events and corresponding waterlogging results was constructed. Several years of practice have demonstrated that a rich library of scenarios can be used effectively for the quick identification and early warning of waterlogging risk for a forecast rainfall. Test results show that multi-mode surface generalization is effective in improving outcomes and useful for scientific decision making in controlling urban waterlogging.

Recently, increasing evidence has displayed that lncRNAs can exhibit crucial function in cancer progression, including lung cancer. LncRNA bladder cancer-associated transcript 1 (BLACAT1) is reported to participate in various cancers. The aim of our current study was to investigate the function of BLACAT1 in non-small cell lung cancer progression and study the functional pathway. Here, we reported BLACAT1 was significantly up-regulated in lung cancer tissues in comparison to the adjacent normal tissues, which suggested BLACAT1 might act as an oncogene in lung cancer. Then, A549 and PC9 cells were infected with BLACAT1 overexpression plasmid and shRNA. As shown, we proved up-regulation of BLACAT1 greatly induced the growth of non-small cell lung cancer cells. Reversely, knockdown of BLACAT1 reduced A549 and PC9 cell proliferation, migration and invasion. Sonic hedgehog (shh) signaling is able to exert a significant role in carcinogenesis, including lung cancer. Currently, we proved that up-regulation of BLACAT1 activated shh signaling pathway, via inducing shh, Gli-1 and Smo expression. shh pathway inhibitor GANT-61 reversed the effect of overexpression of BLACAT1 on non-small cell lung cancer. Moreover, we manifested that loss of BLACAT1 remarkably reduced the in vivo growth and metastasis of A549 cells via enhancing infiltrating CD3+ T cells. In conclusion, our research revealed a critical role of BLACAT1 in the modulation of non-small cell lung cancer via modulating shh pathway.

Yaw system is an important part of wind turbine control system, yaw error is an important performance index of wind turbine, which has great influence on power generation. The wind utilization and the output of the power generation have been determined by the yaw error. In order to make the wind turbine better aligned toward the wind direction, reduce the yaw error, and increase the power generated by the unit, the angle errors of yaw control of wind turbine have been analyzed, in this paper, and the method of wind test, the strategy of yaw control have been studied respectively. Based on the results of the study, the method of wind test, the restart control strategy of yaw system and the performance of control strategy of yaw system have been optimized in this paper. In this way, the three important links are optimized, it will effectively reduce the yaw error as well as significantly improve the wind turbine generating electricity.

Vitamin A deficiency (VAD) remains a public health issue worldwide, affecting pregnant women and children. The early-life microbiota is a potentially effective intervention target for modulating immune and metabolic development of the host. This paper investigates the effects of VAD during different life periods on the structure of the colonic mucosa microbiota in adolescent rats. The results showed that the concentrations of serum retinol were > ~1.05 μmol/L in maternal VA normal (VAN)rats and < 0.7 μmol/L in maternal VAD rats, while the serum retinol levels were higher than 0.7 μmol/L in the pups of the VAN group and below 0.5 μmol/L in the pups of the VAD group. Compared to the offspring persistent with VAN from embryonic stage (group A), all the remaining groups exhibited an increased ratio of Firmicutes/Bacteroidetes abundance. A metagenome analysis (LEfSe) and a differentially abundant features approach using Metastats for genus abundances revealed that Diaphorobacter and Psychrobacter were increased in the offspring persistent with VAD from embryonic stage (group B);Bifidobacterium was decreased and Staphylococcus was increased in the offspring with VAD after weaning (group C); Propionibacterium and Enterobacter were increased significantly in the offspring with VAD during gestation(group E); and Ochrobactrum was increased in group B and the offspring with VAD during gestation and lactation(group D). Faecalibacterium abundance was significantly and positively related to serum retinol levels, while that of Staphylococcus was significantly and negatively correlated with serum retinol levels. VAD in different life periods can alter the gut microbiome in rats, but VAD in the early-life periods (especially gestation and/or lactation) leads to a diversity of the colonic mucosal microbiota in adolescent rats as well as an imbalance of the ratio between Firmicutes and Bacteroidetes. The early-life period may become a time window of VA intervention to improve intestinal microbiota caused by VA deficiency, but the specific mechanism requires more in-depth research.

Over a half century, organ transplantation has become an effective method for the treatment of end-stage visceral diseases. Although the application of immunosuppressants (IS) minimizes the rate of allograft rejection, the common use of IS bring many adverse effects to transplant patients. Moreover, true transplant tolerance is very rare in clinical practice. Dendritic cells (DCs) are thought to be the most potent antigen-presenting cells, which makes a bridge between innate and adaptive immunity. Among their subsets, a small portion of DCs with immunoregulatory function was known as tolerogenic DC (Tol-DC). Previous reports demonstrated the ability of adoptively transferred Tol-DC to approach transplant tolerance in animal models. In this study, we summarized the properties, ex vivo generation, metabolism, and clinical attempts of Tol-DC. Tol-DC is expected to become a substitute for IS to enable patients to achieve immune tolerance in the future.

Tilianin, a representative flavonoid ingredient of Dracocephalum moldavica L., has been used to treat several diseases for centuries, including atherosclerosis (AS). However, pharmacological mechanisms underlying its biological functions remain elusive. In the present study, we investigated the anti-AS mechanisms of tilianin through establishing in vitro models using three types of cells that contributed to AS progression, including macrophage, vascular smooth muscle cells and human umbilical vein endothelial cells, which were proved to be involve in LPS/TNF-α/oxidized low density lipoprotein (ox-LDL)-induced inflammation and ox-LDL induced foam cell formation. Our results indicate that tilianin significantly suppressed LPS induced inflammatory responses on macrophage and remarkably inhibited TNF-α induced VSMCs proliferation and migration. Furthermore, the anti-inflammatory effect of tilianin on macrophages and VSMCs was proved to be mainly by downregulating TNF-α/NF-κB pathway. Moreover, our results demonstrate that tilianin significantly ameliorated ox-LDL induced macrophages oriented foam cells formation through repressing mRNA expression of SR-A1 and inducting the expression of genes related to cholesterol efflux including SRB-1 and ABCA1. However, tilianin had no effect on ox-LDL induced HUVECs injury.

Objectives: Schizophrenia (SZ), major depressive disorder (MDD), and bipolar disorder (BD) are serious mental disorders with distinct diagnostic criteria. They share common clinical and biological features. However, there are still only few studies on the common and specific brain imaging changes associated with the three mental disorders. Therefore, the aim of this study was to identify the common and specific functional activity and connectivity changes in SZ, MDD, and BD.Methods: A total of 271 individuals underwent functional magnetic resonance imaging: SZ (n = 64), MDD (n = 73), BD (n = 41), and healthy controls (n = 93). The symptoms of SZ patients were evaluated by the Positive and Negative Syndrome Scale. The Beck Depression Inventory (BDI), and Beck Anxiety Inventory (BAI) were used to evaluate the symptoms of MDD patients. The BDI, BAI, and Young Mania Rating Scale were used to evaluate the symptoms of MDD and BD patients. In addition, we compared the fALFF and functional connectivity between the three mental disorders and healthy controls using two sample t-tests.Results: Significantly decreased functional activity was found in the right superior frontal gyrus, middle cingulate gyrus, left middle frontal gyrus, and decreased functional connectivity (FC) of the insula was found in SZ, MDD, and BD. Specific fALFF changes, mainly in the ventral lateral pre-frontal cortex, striatum, and thalamus were found for SZ, in the left motor cortex and parietal lobe for MDD, and the dorsal lateral pre-frontal cortex, orbitofrontal cortex, and posterior cingulate cortex in BD.Conclusion: Our findings of common abnormalities in SZ, MDD, and BD provide evidence that salience network abnormality may play a critical role in the pathogenesis of these three mental disorders. Meanwhile, our findings also indicate that specific alterations in SZ, MDD, and BD provide neuroimaging evidence for the differential diagnosis of the three mental disorders.

C-di-GMP has been well investigated to play significant roles in the physiology of many Gram-negative bacteria. However, its effect on Gram-positive bacteria is less known. In order to more understand the c-di-GMP functions in Gram-positive bacteria, we have carried out a detailed study on the c-di-GMP-metabolizing enzymes and their physiological functions in Bacillus thuringiensis, a Gram-positive entomopathogenic bacterium that has been applied as an insecticide successfully. We performed a systematic study on the ten putative c-di-GMP-synthesizing enzyme diguanylate cyclases (DGCs) and c-di-GMP-degrading enzyme phosphodiesterases (PDEs) in B. thuringiensis BMB171, and artificially elevated the intracellular c-di-GMP level in BMB171 by deleting one or more pde genes. We found increasing level of intracellular c-di-GMP exhibits similar activities as those in Gram-negative bacteria, including altered activities in cell motility, biofilm formation, and cell-cell aggregation. Unexpectedly, we additionally found a novel function exhibited by the increasing level of c-di-GMP to promote the insecticidal activity of this bacterium against Helicoverpa armigera. Through whole-genome transcriptome profile analyses, we found that 4.3% of the B. thuringiensis genes were differentially transcribed when c-di-GMP level was increased, and 77.3% of such gene products are involved in some regulatory pathways not reported in other bacteria to date. In summary, our study represents the first comprehensive report on the c-di-GMP-metabolizing enzymes, their effects on phenotypes, and the transcriptome mediated by c-di-GMP in an important Gram-positive bacterium.

Background: Metabolic reprogramming is a feature of cancer. However, colon cancer subtypes based on the glycolysis-cholesterol synthesis axis have not been identified, and little is known about connections between metabolic features and the tumor microenvironment. Methods: Data for 430 colon cancer cases were extracted from The Cancer Genome Atlas, including transcriptome data, clinical information, and survival outcomes. Glycolysis and cholesterol synthesis-related gene sets were obtained from the Molecular Signatures Database for a gene set variation analysis. The relationship between the genomic landscape and immune landscape were investigated among four metabolic subtypes. Hub genes were determined. The clinical significance of candidate hub gene was evaluated in 264 clinical samples and potential functions were validated in vitro and in vivo. Results: Colon cancer cases were clustered into four metabolic subtypes: quiescent, glycolytic, cholesterogenic, and mixed. The metabolic subtypes differed with respect to the immune score, stromal score, and estimate score using the ESTIMATE algorithm, cancer-immunity cycle, immunomodulator signatures, and signatures of immunotherapy responses. Patients in the cholesterogenic group had better survival outcomes than those for other subtypes, especially glycolytic. The glycolytic subtype was related to unfavorable clinical characteristics, including high mutation rates in TTN, APC, and TP53, high mutation burden, vascular invasion, right colon cancer, and low-frequency microsatellite instability. GGH, CACNG4, MME, SLC30A2, CKMT2, SYN3, and SLC22A31 were identified as differentially expressed both in glycolytic-cholesterogenic subgroups as well as between colon cancers and healthy samples, and were involved in glycolysis-cholesterol synthesis. GGH was upregulated in colon cancer; its high expression was correlated with CD4+ T cell infiltration and longer overall survival and it was identified as a favorable independent prognostic factor. The overexpression of GGH in colon cancerderived cell lines (SW48 and SW480) inhibited PKM, GLUT1, and LDHA expression and decreased the extracellular lactate content and intracellular ATP level. The opposite effects were obtained by GGH silencing. The phenotype associated with GGH was also validated in a xenograft nude mouse model. Conclusions: Our results provide insight into the connection between metabolism and the tumor microenvironment in colon cancer and provides preliminary evidence for the role of GGH, providing a basis for subsequent studies. [ABSTRACT FROM AUTHOR]

Backgrounds: Compared with previously published meta-analyses, this is the first study to investigate the combined effects of glutathione-S-transferase polymorphisms (GSTM1, GSTT1 and GSTP1 IIe105Val) and type 2 diabetes mellitus (T2DM) risk; moreover, the credibility of statistically significant associations was assessed; furthermore, many new original studies were published. Objectives: To determine the relationship between GSTM1, GSTT1, and GSTP1 polymorphisms with T2DM risk. Methods: PubMed, Embase, Wanfang, and China National Knowledge Infrastructure Databases were searched. We quantify the relationship using crude odds ratios and their 95% confidence intervals Moreover, the Venice criteria, false-positive report probability (FPRP), and Bayesian false discovery probability (BFDP) were used to validate the significance of the results. Results: Overall, significantly increased T2DM risk was found between individual and combined effects of GSTM1, GSTT1, and GSTP1 polymorphisms on T2DM risk, but, combined effects of the GSTT1 and GSTP1 polymorphisms was not statistically significant. GSTT1 gene polymorphism significantly increases the risk of T2DM complications, while GSTM1 and GSTP1 polymorphisms had no statistical significance. The GSTM1 null genotype was linked to a particularly increased risk of T2DM in Caucasians; the GSTT1 null genotype was connected to a significantly higher risk of T2DM in Asians and Indians; and the GSTP1 IIe105Val polymorphism was related to a substantially increased T2DM risk in Indians. Moreover, the GSTM1 and GSTT1 double null genotype was associated with substantially increased T2DM risk in Caucasians and Indians; the combined effects of GSTM1 and GSTP1 polymorphisms was associated with higher T2DM risk in Caucasians. However, all significant results were false when the Venice criteria, FPRP, and BFDP test were used (any FPRP >0.2 and BFDP value >0.8). Conclusion: The current analysis strongly suggests that the individual and combined effects of GSTM1, GSTT1 and GSTP1 polymorphisms might not be connected with elevated T2DM risk. [ABSTRACT FROM AUTHOR]

Background: Dyslipidemia is a well-recognized risk factor for diabetic kidney disease (DKD) in patients with type 2 diabetes (T2D). Growing evidences have shown that compared with the traditional lipid parameters, some lipid ratios may provide additional information of lipid metabolism. Thus, the present study aimed to investigate which lipid index was most related to DKD. Methods: This study was a cross-sectional study that enrolled patients with T2D from January 2021 to October 2021. Each participant was screened for DKD, and the diagnostic criterion for DKD is estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73 m2 or urinary albumin-to-creatinine ratio (UACR) = 30 mg/g for 3 months. Fasting blood was collected to determine lipid profiles by an automatic biochemical analyzer, and lipid ratios were calculated based on corresponding lipid parameters. Spearman's correlation analyses were conducted to assess the correlations between lipid indices and kidney injury indices, and binary logistic regression analyses were conducted to explore the relationship between lipid indices and the risk of DKD. Results: A total of 936 patients with T2D were enrolled in the study, 144 (15.38%) of whom had DKD. The LDL-C/Apo B ratios were positively correlated with eGFR (r = 0.146, p < 0.05) and inversely correlated to cystatin C and UACR (r = -0.237 and -0.120, both p < 0.001). Multiple logistic regression demonstrated that even after adjusting for other clinical covariates, the LDL-C/Apo B ratios were negatively related to DKD, and the odds ratio (95% confidence interval) was 0.481 (0.275-0.843). Furthermore, subgroup analyses revealed that compared with patients with normal lipid profiles and a high LDL-C/Apo B ratio, the odds ratio of DKD in patients with normal lipid metabolism and a low LDL-C/Apo B ratio was 2.205 (1.136-4.280) after adjusting for other clinical covariates. Conclusion: In patients with T2D, the LDL-c/Apo B ratio was most closely associated with DKD among various lipid indices, and a lower LDL-C/Apo B ratio was associated with increased risks of DKD among patients with T2D. [ABSTRACT FROM AUTHOR]