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Abstract The Li-enriched oilfield brine is a very important lithium resource. It has gained much attention and become the target of active Li surveys with the growing global demand for Li. However, only little is known about their feature and nature. In the study, hydrochemical data from 155 oil wells tapping the Eocene to Lower Oligocene Qianjiang Formation of the Jianghan Basin, central China indicate that the brines are of the Na–Cl or Na–Ca–Cl type and are characterized by highly variable Li contents of 7.56 to 150 mg/L, with Mg/Li ratios less than 11.65. High Na/Cl and Cl/Br molar ratios indicate distinct contributions from halite dissolution. The Ca excess, Na deficit and Ca/Mg and Ca/Sr molar ratios in the brines imply multiple diagenetic processes, including halite dissolution, dolomitization, albitization and calcite or anhydrite cementation. The lithium contents of these brines have a weak relationship with the salinity and a negative correlation with Cl/Br ratios, possibly indicating that these Qianjiang oilfield brines have been diluted by secondary brines derived from halite dissolution. The spatial distribution patterns for Li and B concentrations of the brines are different from those for salinity and Br contents and show a geographic pattern, indicating that Li enrichment in the Qianjiang brines is likely connected with geothermal sources associated with volcanic activity.

Abstract Objective Gestational diabetes mellitus (GDM) is a serious complication in pregnancy. Despite controlling the plasma glucose levels with dietary intervention (GDM-D) or insulin therapy (GDM-I), children born of diabetic mothers suffer more long-term complications from childhood to early adulthood. Placental circulation and nutrient exchange play a vital role in fetal development. Additionally, placental endothelial function is an indicator of vascular health, and plays an important role in maintaining placental circulation for nutrient exchange. This study was conducted to assess changes in fetal endothelial dysfunction in GDM under different interventions during pregnancy. Methods The primary human umbilical vein endothelial cells (HUVECs) were obtained from normal pregnant women (n = 11), GDM-D (n = 14), and GDM-I (n = 12) patients. LC-MS/MS was used to identify differentially expressed proteins in primary HUVECs among the three groups, after which Bioinformatics analysis was performed. Glucose uptake, ATP level, apoptosis, and differentially expressed proteins were assessed to investigate changes in energy metabolism. Results A total of 8174 quantifiable proteins were detected, and 142 differentially expressed proteins were identified after comparing patients with GDM-D/GDM-I and healthy controls. Of the 142, 64 proteins were upregulated while 77 were downregulated. Bioinformatics analysis revealed that the differentially expressed proteins were involved in multiple biological processes and signaling pathways related to cellular processes, biological regulation, and metabolic processes. According to the results from KEGG analysis, there were changes in the PI3K/AKT signaling pathway after comparing the three groups. In addition, there was a decrease in glucose uptake in the GDM-I (P

Objective: This study aimed to compare the efficiency of these two combined surgeries [prolapse and hemorrhoids (PPH) combined with the external hemorrhoidectomy and inferior internal hemorrhoid ligation; tissue selecting technique with mega-window stapler (TST-MS) combined with anal canal epithelial preservation operation]. Methods: This is a single-center, evaluator-blinded randomized controlled trial (RCT). A total of 204 participants were randomly divided into the two groups. The anal function, reoccurrence, intraoperative variables, and operative complications were assessed. The measurement data were compared by paired t test and rank sum test. Chi-squared or Fisher's exact test was used for count data and rank sum test for ranked data. To assess differences within each group in different time points, the repeated-measures analysis of variance was conducted. Results: TST-MS combined with anal canal epithelial preservation operation had lower Wexner score of anal incontinence (Z = 3.062, P = 0.002), higher patients’ satisfaction degree (t = 7.32, P 0.05). Conclusions: TST-MS combined with anal canal epithelial preservation operation showed better clinical efficiency in the treatment of prolapsed hemorrhoids. Trial registration: This study has been registered in Chinese Clinical Trial Registry (ChiCTR2000038533)

Disc buckle steel pipe brackets are widely used in building construction due to the advantages of its simple structure, large-bearing capacity, rapid assembling and disassembling, and strong versatility. In complex construction projects, the uncertainties affecting the stability of disc buckle steel pipe support need to be considered to ensure the safety of disc buckle steel pipe supports. A surrogate model based on a deep neural network is built and trained to predict the ultimate load-carrying capacity of a stent. The results of the finite element model calculations are used to form the sample set of the surrogate model. Then, we combined the computationally efficient DNN surrogate model with the Monte Carlo method to consider the distribution of the ultimate load capacity of the disc buckle bracket under the uncertainties of the bracket node pin wedge tightness, the wall thickness of the steel pipe, and the connection of the connecting wall member. At the same time, based on the DNN model, the SHapley Additive exPlanations (SHAP) interpretability analysis method was used to study the degree of influence of various uncertainty factors on the ultimate bearing capacity of the stent. In practical engineering, the stability analysis of a disc buckle tall formwork support has shown that a surrogate model based on a deep neural network is efficient in predicting the buckling characteristic value of the support. The error rate of the prediction is less than 2%. The buckling characteristic values of the bracket vary in the range of 17–25. Among the various factors that influence the buckling characteristic value of the bracket, the joint wedge tightness has the greatest impact, followed by the bottom and top wall-connecting parts.

Commutation failures in high-voltage direct current (HVDC) transmission systems often occur within inverter stations, posing challenges to the safe and consistent operation of HVDC transmission projects. This paper examines data gathered from a wide-spectrum transient electromagnetic voltage monitoring apparatus. The findings uncover a notable correlation between transient AC bus voltage disturbances, stemming from faults, and the occurrence of commutation failures in HVDC transmission systems. Leveraging this correlation, we propose a commutation failure mitigation strategy for HVDC systems centered around AC bus voltage disturbances within inverter stations. Through fault validation simulations conducted across three HVDC transmission systems, our strategy demonstrates effective suppression of commutation failure incidents within HVDC transmission projects.

The supply and reserves of emergency necessities of life are important for emergency management in disaster events. The scope of the necessities of life changes with social development, and their reserves and allocation in sudden disaster events continually face new challenges. Timely distribution of the necessities of life during disasters is critical to saving lives and maintaining social order. Therefore, this study proposes a fractal multi-level distribution network (FMDN) optimization model with multiple warehouse points, multiple emergency distribution centers, and multiple disaster points from the perspective of fractal theory. The FMDN model considers the influence of road damage on vehicle speed and the dynamic change in demand at the affected points. The FMDN model aims to minimize the operating costs of a distribution network, including the cost of building emergency reserve points, transportation costs, and penalty costs for lack of demand. Numerical experiments verify the feasibility of the model. The FMDN model is solved using LINGO software programming, and an optimal distribution path and quantity are obtained. Analyzing the numerical example results shows that the model is suitable for emergencies and has good applicability.

Abstract Network function virtualization (NFV) is an appealing solution that transforms complex network functions from dedicated hardware to software instances running in a virtualized environment. However, some new challenges will arise when deploying virtual network functions to meet the needs of NFV and edge‐computing (EC) enabled 5G networks. In this paper, we focus on the service function chain (SFC) orchestration problem for EC‐enabled networks to maximize the profit of network service providers. First, the mathematical model of SFC orchestration in NFV and EC‐enabled networks is defined. Then, a two‐stage heuristic algorithm is proposed to optimize the total revenue. Finally, the performance of the method is evaluated by simulation experiments and the results show its effectiveness.

ObjectiveThe prevalence of mental distress has been noted in shelter hospitals set up for COVID-19. Potential risk demographic and hospitalization factors were screened. We also aimed to determine whether humanistic care established in the shelter hospital was effective in ameliorating mental distress.MethodsA cross-sectional observational survey-based single-centered study was conducted from 28th April to 5th May 2022 during the COVID-19 pandemic in Shanghai. Asymptomatic adult inpatients and those with mild symptoms were recruited for this study, and humanistic care measures were carried out by the administrative office according to the Work Program on Psychological Assistance and Social Work Services at the Shelter Hospital launched on 5th March 2020. Symptoms of mental distress, such as reported stress, anxiety, depression, and insomnia were measured using the Chinese Stress Response Questionnaire-28, the Chinese version of Generalized Anxiety Disorder-7, Patient Health Questionnaire-9, and Insomnia Severity Index-7, respectively.ResultsIn total, 1,246 out of 9,519 inpatients, including 565 (45.35%) women and 681 (54.65%) men, with a median age of 36 years responded to the survey. The overall prevalence of stress, anxiety, depression, and insomnia in inpatients was 94 (7.54%), 109 (8.75%), 141 (11.32%), and 144 (11.56%), respectively. Mental distress was aggravated by COVID-19-related symptoms, comorbidities, and prolonged hospital stays. A stable internet connection was the most effective measure to reduce stress and depression. Offering inpatient with study or work facilitations, and mental health education help to ameliorate anxiety and depression. Organizing volunteering was a potential protective factor against stress.ConclusionHumanistic care is crucial and effective for protecting against mental distress, which should be emphasized in shelter hospitals.

[Introduction] In the power system, the surge arrester in switchgear plays an important role in suppressing transient overvoltage and discharging large pulse currents, which is of great significance to maintain its normal and stable operation. [Method] A time-frequency analysis method based on the autocorrelation coefficient and the Chi-squared test optimization was proposed in the research to effectively suppress the noise interference on leakage current signal detection. Firstly, the measurement results of the current sensor and the shunt were analyzed. Then, the wavelet transform based on the autocorrelation coefficient and the Chi-squared test optimization was used to eliminate the noise interference in the signal in order to determine the optimal decomposition size to better suit the occasion of small signal-noise ratio. [Result] Based on the analysis in the software platform, it is concluded that the optimized wavelet algorithm denoising has stronger anti-interference capability and better waveform quality on the basis of measurement of the shunt. Finally, an online leakage current detection device is developed to verify the leakage current detection model proposed in the research. [Conclusion] The experimental results show that the device can realize the real-time detection of leakage current of the surge arresters.

The group of Shih-Yin Tsai observed age-associated neuromuscular junction structural instability in male but not female mice which is driven by dysregulation of mTOR complex 1 activity. Genetic activation of the downstream phosphorylation target 4EBP1 in the muscle remodeled the neuromuscular junction and enhanced synaptic transmission.

Abstract Background Kikuchi-Fujimoto disease (KFD) is a self-limiting and benign disease characterized by cervical lymphadenopathy and fever. Although KFD should be made differentially diagnosed from infectious, autoimmune, and malignant diseases, it sometimes occurs in patients with systemic lupus erythematosus (SLE) and can be complicated with macrophage activation syndrome (MAS). However, it is rare that KFD is the initial manifestation of SLE and to be complicated with MAS. Case presentation A 9.6-year-old girl presented with high-grade fever, double-side cervical lymphadenopathy with mild pain of one week, leukopenia, alopecia, and rash on the cheek. During hospitalization, laboratory investigations showed positive antinuclear antibody (ANA), low complement 3 (C3), and low complement 4 (C4). Imaging investigations showed pleural and pericardial effusion. A 10.3-year-old girl presented with intermittent high-grade fever, double-sided cervical lymphadenopathy with obvious pain of 1-month duration, and discoid lesion on the cheek. During hospitalization, laboratory investigations showed positive ANA, leukopenia, thrombocytopenia, anemia with positive Coombs’ test, low C3, and positive Smith antibodies. Both cases were diagnosed with KFD using lymph node biopsy, simultaneously fulfilling the diagnostic criteria of SLE. Subsequently, the two girls became complicated with MAS, followed by interstitial lung disease and neuropsychiatric lupus, respectively. Both patients benefited from high-dose methylprednisolone pulse therapy combined with intravenous cyclophosphamide. Conclusions More attention should be paid to differential diagnosis, especially SLE, in children diagnosed with KFD. In addition, children with SLE who presented with KFD as the initial manifestation seem to have a higher risk of developing MAS and experiencing organ involvement.

Abstract Background To evaluate the therapeutic effect of maxillary pad movable appliance combined with FR-III functional appliance in treating skeletal Class III malocclusion of deciduous teeth and provide a reference for optimizing clinical treatment methods. Methods A total of 30 pediatric patients were randomly selected between April 2012 and April 2019. They were in stage IIA osseous skeletal Class III malocclusion, treated with maxillary pad movable appliance to relieve the reverse, combined with FR-III functional appliance to maintain a median relationship to stage IIIA. A self-control study of children before and after treatment was used, and paired t-test was used to evaluate the changes in the measurement indexes of the IIA and IIIA stage X-rays and changes in the bone and soft tissue profiles. Results After 3 years of treatment, SNA, ANB, and NA-PA in the sagittal osteofacial index of the jawbones increased, SNB decreased, and the Y-axis angle in the vertical index of the jawbones increased. U1-SN, U1-NA, U1-NA distance, L1-MP, L1-NB, and L1-NB distance in the index of labial inclination of upper and lower central incisors increased, while U1-L1 decreased. The sagittal anomalies of the jawbones were improved, and there were significant differences before and after treatment (P

Abstract Background Dental caries is one of the most prevalent chronic diseases worldwide among children. The rs35874116 single nucleotide polymorphism (SNP) in the sweet receptor gene TAS1R2 has been associated with dental caries at a high risk in permanent teeth among school children and adults. To date, little is known about the association of this SNP with sweet intake and caries risk in the primary school children. Methods Total of 236 children were included, namely 118 subjects in the non-caries (NC) group and severe early childhood caries (S-ECC) group, respectively. Oral mucosa cells were collected from all the selected children, and the full length of exon 3 in TAS1R2 was sequenced to analyse rs35874116 polymorphism. A questionnaire was used to collect information about socio-demographic information, frequency of sweet intake and oral hygiene habits. Multiple logistic regression models were applied to assess the relationship of rs35874116 polymorphism with frequency of sweet intake and S-ECC among the five-year-old children. Results Children with the TT genotype of rs35874116 had a higher frequency of sweet intake than CT/CC carriers (51.3% vs. 32.7%; x 2 = 5.436, p = 0.020), and S-ECC individuals were more likely to be TT genotype carriers than NC individuals (53.5% vs. 46.5%; x 2 = 4.353, p = 0.037). Multiple logistic regression analyses showed that the TT genotype of rs35874116 was not only significantly related to the frequency of sweet intake (OR = 2.25, 95% CI = 1.14–4.44) but also significantly associated with S-ECC (OR = 2.11, 95% CI = 1.01 ~ 4.42). Conclusions The rs35874116 polymorphism might increase sweet intake and the risk of S-ECC among five-year-old children in Nanning, China.

Background and objective Lung cancer is the main cause of cancer-related death globally. Single nucleotide polymorphism (SNP) is one of the important factors leading to the occurrence of lung cancer, but its mechanism has not been elucidated. This study intends to investigate the relationship between SNPs of CDH1, FANCB, APC genes and lung cancer genetic susceptibility. Methods The case-control study design was used. We collected blood samples from 270 lung cancer cases in the Department of Lung Cancer Surgery, Tianjin Medical University General Hospital, as well as blood samples from 445 healthy volunteers as controls, and extracted genomic DNA for genotyping using the Taqman® SNP genotyping kit. The distribution of three SNP loci of CDH1 gene rs201141645, FANCB gene rs754552650 and APC gene rs149353082 in Chinese population was analyzed. Chi-square test and Logistic regression were used to analyze the relationship between different genotypes and the risk of lung cancer. Results The distribution frequencies of AA, A/G and GG genotypes at rs754552650 of FANCB gene in the control group were 27.2%, 52.6% and 20.2%, respectively. The distribution frequencies of AA and A/G genotypes were 93.7% and 6.3% in the case group, respectively, and no GG genotype was detected. The A/G genotype of the rs754552650 locus of the FANCB gene was significantly different between the case group and the control group. Compared with the carriers of AA genotype, the individuals with FANCB rs754552650 A/G genotype had a lower risk of lung cancer (OR=0.035, 95%CI: 0.020-0.062, P

Objective: To define the properties of lung cancer cells that resisted conventionally fractionated radiation exposure. Methods: Acquired radioresistant lung cancer cell line A549 was constructed by X-ray irradiation with a clinical conventional fraction dose of 2 ​Gy daily during 30 fractions. Cell morphology, molecular markers, migration capacity and invasion potential were evaluated by the microscope, Western blot, immunofluorescence, wound healing test and transwell chamber assay, respectively. Results: Radioresistant A549 ​cells shifted from an epithelial to a mesenchymal morphology, termed as epithelial-mesenchymal transition (EMT), and was accompanied by decreased expressions of epithelial markers (F ​= ​4.568, P ​

Abstract Background Pulmonary complications of rheumatic diseases may cause functional impairment and increase mortality. However, reports regarding detection of lung involvement in children with treatment-naive, newly diagnosed rheumatic diseases are scarce. Herein, we aimed to describe the characteristics of such patients and explore the association between lung involvement and rheumatic disease. Methods From January 2019 to June 2021, 48 pediatric patients with treatment-naive, newly diagnosed rheumatic diseases at Department of Rheumatology and Immunology, Shanghai Children's Medical Center, School of Medicine, Shanghai Jiao Tong University were included with pulmonary function tests (PFTs) and high-resolution computed tomography (HRCT) findings, and 51 age-matched healthy controls were examined based on PFTs. Univariate and multivariable logistic regression analyses were used to investigate the clinical characters and laboratory parameters associated with lung involvement in these patients. Results Asymptomatic patients had a faster respiratory rate and a higher ratio of forced expiratory volume in 1 s/forced vital capacity than the controls (P

In this work, we have successfully fabricated Sr-doped porous LaFeO3 samples via sol–gel method. The results reveal that Sr2+ cation is effectively doped into LaFeO3 crystal lattice substituting La3+ cation. The visible light catalytic performance of the materials was evaluated by the degradation of 2,4-dichlorophenol (2,4-DCP) and Rhodamine B (RhB). The amount-optimized Sr-doped porous LaFeO3 sample exhibited outstanding visible-light catalytic performance for the degradation of the model pollutants compared to the porous LaFeO3 alone. The enhanced performance was accredited to the enlarged surface area, absorption extension via the surface states of the introduced Sr2+ below the conduction band bottom of LaFeO3, and promoted charge carrier’s separation as confirmed by various experiments. Experiments of radical trapping reveal that •OH species are dominant intermediate oxidants involved in the oxidation of 2,4-DCP and RhB over the optimized sample. This research will provide new routes for environmental remediation based on the LaFeO3 semiconductor.

Inflammation is believed to play a role in the progression of numerous human diseases. Research has shown that inflammation and telomeres are involved in a feedback regulatory loop: inflammation increases the rate of telomere attrition, leading to telomere dysfunction, while telomere components also participate in regulating the inflammatory response. However, the specific mechanism behind this feedback loop between inflammatory signaling and telomere/telomerase complex dysfunction has yet to be fully understood. This review presents the latest findings on this topic, with a particular focus on the detailed regulation and molecular mechanisms involved in the progression of aging, various chronic inflammatory diseases, cancers, and different stressors. Several feedback loops between inflammatory signaling and telomere/telomerase complex dysfunction, including NF-κB-TERT feedback, NF-κB-RAP1 feedback, NF-κB-TERC feedback, STAT3-TERT feedback, and p38 MAPK-shelterin complex-related gene feedback, are summarized. Understanding the latest discoveries of this feedback regulatory loop can help identify novel potential drug targets for the suppression of various inflammation-associated diseases.

This study describes a novel species of Gekko (Squamata: Gekkonidae) based on its distinct morphological features and molecular evidence, which was identified in the Dabie Mountains on the border of Anhui and Henan provinces of Central China. Gekko kaiyai sp. nov. could be distinguished from its congeners owing to its morphological characteristics, such as being a medium body sized gecko species (snout–vent length, 56.98–64.99 mm, n = 4, females; 50.03–61.56 mm, n = 11, males); nostrils scale in contact with rostral scale; tubercles on the dorsal and limb, while the upper forelimb is smooth with no tubercles; 22–33 interorbital scales between the anterior corners of the eyes; 157–209 ventral scales between mental and cloacal slit; 90–121 midbody scale rows; 30–43 ventral scale rows; 7–9 sub-digital lamellae on first fingers, 8–13 fourth fingers, 7–9 first toes, and 7–11 fourth toes; free of webbing in the fingers and toes; 9–12 pre-cloacal pores in males, which are absent in females; post-cloacal unilateral tubercles 1 (few 2); and a dorsum that is greyish white to dark brown, with 6–7 brown markings between the nape and sacrum. The phylogenetic tree based on the mitochondrial DNA sequences (16S, CYTB, and COI) indicated that Gekko kaiyai sp. nov. form an independent clade with strong support (100/1) and are a sister group to G. hokouensis. At the inter-species level, the genetic distances were all large, further confirming that an independent species had been identified. The discovery of this species implies that there are now 87 identified species in the genus Gekko, 22 of which can be found within China.

Crystalline solid dispersions (CSDs) represent a thermodynamically stable system capable of effectively reducing the crystallite size of drugs, thereby enhancing their solubility and bioavailability. This study uses flavonoid drugs with the same core structures but varying numbers of hydroxyl groups as model drugs and poloxamer 188 as a carrier to explore the intrinsic relationships between drug–polymer interactions, crystallite size, and in vitro dissolution behavior in CSDs. Initially, we investigate the interactions between flavonoid drugs and P188 by calculating Hansen solubility parameters, determination of Flory–Huggins interaction parameters, and other methods. Subsequently, we explore the crystallization kinetics of flavonoid drugs and P188 in CSD systems using polarized optical microscopy and powder X-ray diffraction. We monitor the domain size and crystallite size of flavonoids in CSDs through powder X-ray diffraction and a laser-particle-size analyzer. Finally, we validate the relationship between crystallite size and in vitro dissolution behavior through powder dissolution. The results demonstrate that, as the number of hydroxyl groups increases, the interactions between drugs and polymers become stronger, making drug crystallization in the CSD system less likely. Consequently, reductions in crystalline domain size and crystallite size become more pronounced, leading to a more significant enhancement in drug dissolution.

Abstract Background Perioperative chemotherapy (ChT) and preoperative chemoradiation (CRT) are both the standard treatments for locally advanced gastric cancer (LAGC). CRT can achieve a higher pathological complete regression (pCR) rate, but whether this higher pCR rate can be transformed into a long-term survival benefit remains inconclusive. Therefore, relevant studies are in progress. On the other hand, immunotherapy has been established for the first-line treatment of advanced gastric cancer (AGC) and has been widely explored in the perioperative setting. The combination of chemotherapy/radiotherapy and immunotherapy may have a synergistic effect, which will lead to a better antitumor effect. The preliminary reports of ongoing studies show promising results, including a further improved pCR rate. However, the preferred treatment combination for LAGC is still not established. To solve this problem, we are carrying out this randomized phase II trial, which aims to evaluate the efficacy and safety of perioperative chemotherapy plus the use of PD-1 antibody with or without preoperative chemoradiation for LAGC. Methods Eligible patients with LAGC or gastroesophageal junction (GEJ) adenocarcinoma were randomized to receive perioperative ChT, PD-1 antibody, surgery with (Arm A) or without preoperative CRT (Arm B), and PD-1 antibody maintenance until one year after surgery. The primary endpoint of this study is that the pCR rate of Arm A will be significantly higher than that of Arm B. The secondary endpoints include the pathological partial regression (pPR) rate, R0 resection rate, objective response rate (ORR), event-free survival (EFS), overall survival (OS), safety and surgical complications. Moreover, several explorative endpoints will be evaluated to find and validate the predictive biomarkers of immunotherapy. Discussion The results of the NeoRacing study will provide important information concerning the application of PD-1 antibody in LAGC patients during the perioperative setting. Meanwhile, the two treatment protocols will be compared in terms of efficacy and safety. Trial registration ClinicalTrials.gov , NCT05161572 . Registered 17 December 2021 - Retrospectively registered.

Spleen micro-perfusion level can be evaluated by DDVD (diffusion derived vessel density): DDVD (unit: au/pixel) = Sb0/ROIarea0 – Sb2/ROIarea2, where Sb0 and Sb2 refer to the spleen signal when b is 0 or 2 (s/mm2) and ROI is ‘region-of-interest’. This study investigated whether spleen DDVD is altered in patients with viral hepatitis-b (VHB) liver fibrosis. Three datasets were retrospectively analysed. Shenzhen data-1 had 25 healthy volunteers and 15 VHB liver fibrosis patients. Changsha data had 24 healthy volunteers and 31 patients with VHB liver fibrosis. Shenzhen data-2 had 67 healthy volunteers. Shenzhen data-2 were measured by reader-1. Shenzhen data-1 were measured by reader-1 and reader-2. For Changsha data, reader-1 measured all subjects, while Reader-2 measured a random selection of 10 healthy volunteers and two patients from each liver fibrosis grade (total=8). Shenzhen data-2 showed in healthy volunteers there was no age-dependent change of spleen DDVD during 20 ∼71 years old, and women had higher spleen DDVD values than those of men's (16.17±7.34 vs. 12.88±5.91, p=0.04). Changsha data by reader-1 showed patients with liver fibrosis had lower spleen DDVD values than those of healthy volunteers (median=16.24 vs. 23.54, p=0.0031). Results of reader-2 showed the same trend (median=11.64 vs. 23.33, p=0.0165). Shenzhen data-1 measured by reader-1 showed medians of spleen DDVD for patients and volunteers were 8.535 and 12.33 respectively; and those measured by reader-2 were 13.89 and 14.31 respectively. We conclude that diffusion MRI shows spleen DDVD, i.e., micro-circulation per volume tissue, is decreased in VHB liver fibrosis patients.

The occlusion of shade leads to the intermittent reception of satellite signals, which subsequently results in a decline of the positioning accuracy of Global Navigation Satellite System (GNSS). In order to improve the accuracy of positioning and ensure the continuity of navigation results in weak signal environment, a cubature Kalman Filter (CKF)-based micro-electro mechanical-system (MEMS) grade inertial navigation system (INS) assisted GNSS vector tracking (VT) loop is proposed in this paper. Combining effective GNSS measurements and INS information, attitude, velocity, and position results are predicted by CKF, and the pseudo-range results from navigation filter are fed back into the VT loop. The field tests show that the proposed CKF-based MEMS-INS assisted GNSS VT loop can run continuously and stably in weak signal environment with higher navigation accuracy.

ObjectiveThe effect of vitamin D status on adult COVID-19 pneumonia induced by Delta variant remains to be further explored.MethodsA longitudinal, real-world cohort study was performed. Artificial intelligence (AI) was used to identify and measure pneumonia lesions. All cases with pneumonia were divided into the vitamin D deficiency (VDD) and control groups according to serum 25-hydroxyvitamin D concentration. Lesion dynamics were observed within six time periods after the onset of pneumonia.ResultsA total of 161 cases were included, of which 101 (63%) were male and 46 (29%) presented with pneumonia. The median age and baseline 25-hydroxyvitamin D concentrations were 37 years and 21 ng/ml, respectively. Age, fibrinogen, and SARS-CoV-2 IgG titer on admission were independent predictors for the onset of pneumonia. After the onset of pneumonia, patients in the VDD group (n = 18) had higher percentage of fever (33 vs. 7.1%; p = 0.04) than those in the control group (n = 28); the interval of pneumonia resolution was longer (28 vs. 21 days; p = 0.02); lesions progressed more rapidly (p = 0.01) within 3 to 7 days and improved more slowly (p = 0.007) within more than 28 days; notably, simultaneous interleukin-6 (18.7 vs. 14.6 pg/ml; p = 0.04) levels were higher, and cycle thresholds for N gene (22.8 vs. 31.3; p = 0.04) and ORF1ab gene (20.9 vs. 28.7; p = 0.03) were lower within 3 to 7 days.ConclusionVitamin D status may have effects on the progression and resolution, but not the onset of Delta variant-induced pneumonia in adults. Computed tomography image diagnosis system based on AI may have promising applications in the surveillance and diagnosis of novel SARS-CoV-2 variant-induced pneumonia.

BackgroundIt has been established that the scavenger receptor class A member 5 (SCARA5) functions as a tumor suppressor gene in various cancer types. To our knowledge, no comprehensive study has hitherto investigated the expression and function of SCARA5 in melanoma. This study aimed to determine the association between SCARA5 and melanoma.MethodsAnalysis of SCARA5 mRNA expression was performed using The Cancer Genome Atlas (TCGA) data sets. To evaluate the clinical significance of SCARA5, the clinical data of 93 patients with melanoma were collected. The role of SCARA5 expression in prognosis was also analyzed. In this study, survival was evaluated by Kaplan–Meier analysis and compared using the log-rank test. Univariate and multivariate Cox proportional hazard regression analyses were used to identify independent predictors. The Kyoto Encyclopedia of Genes and Genomes, Gene Ontology, and gene set enrichment analysis (GSEA) were used to perform gene set functional annotations. Protein–protein interaction (PPI) networks were constructed to illustrate gene–gene interactions. The Tumor IMmune Estimation Resource (TIMER) database was used to explore the association between SCARA5 and immune infiltration levels.ResultsThe results showed that the SCARA5 mRNA expression in melanoma was significantly lower than in adjacent normal skin tissue (p < 0.001). Moreover, decreased expression of SCARA5 in melanoma correlated with the tumor, node, and metastasis (TNM) stage and recurrence (p < 0.05). The overall survival (OS) was significantly higher in melanoma with high SCARA5 expression compared with low SCARA5 expression (p < 0.001). During univariate analysis, SCARA5 expression, tumor (T) stage, node (N) stage, metastasis (M) stage, and recurrence correlated with OS (p < 0.05). Further multivariate Cox regression analysis showed that SCARA5 expression (p = 0.012) could be an independent prognostic factor for OS in cutaneous malignant melanoma. GSEA analysis showed that SCARA5 was significantly enriched in various pathways, such as response to developmental biology and response to antimicrobial peptides. Correlation analysis showed a positive correlation with CD8+ T cells, CD4+ T cells, macrophages, neutrophils, and dendritic cells (p < 0.05), and a negative correlation with tumor purity (p < 0.05)ConclusionSCARA5 has significant potential as a prognostic biomarker and as a promising therapeutic target in melanoma. Furthermore, SCARA5 expression in melanoma is related to the level of immune infiltration.

Lichen myxedematosus (LM) is an idiopathic cutaneous mucinosis disorder, and monoclonal gammopathy of undetermined significance (MGUS) is a preneoplastic plasma cell disease with a monoclonal increase in globulin. Patients with LM combined with monoclonal gammopathy are normally diagnosed with scleromyxedema. However, we report a case of generalized papules combined with MGUS in a 78-year-old man who was eventually diagnosed with atypical or intermediate forms of LM because it only involved the skin, and the pathological type was not consistent with scleromyxedema. Few cases of atypical or intermediate forms of LM have been reported, so the course of atypical or intermediate forms of LM is unpredictable. We report the diagnosis and treatment of a case of atypical forms of LM to discuss the current understanding of the disease, hoping to provide a reference for clinical research on this disease.

Background: Breast cancer has the highest incidence among malignant tumors in women, and its prevalence ranks first in global cancer morbidity.Aim: This study aimed to explore the feasibility of a prognostic model for patients with breast cancer based on the differential expression of genes related to fatty acid metabolism.Methods: The mRNA expression matrix of breast cancer and paracancer tissues was downloaded from The Cancer Genome Atlas database. The differentially expressed genes related to fatty acid metabolism were screened in R language. The TRRUST database was used to predict transcriptional regulators related to hub genes and construct an mRNA–transcription factor interaction network. A consensus clustering approach was used to identify different fatty acid regulatory patterns. In combination with patient survival data, Lasso and multivariate Cox proportional risk regression models were used to establish polygenic prognostic models based on fatty acid metabolism. The median risk score was used to categorize patients into high- and low-risk groups. Kaplan–Meier survival curves were used to analyze the survival differences between both groups. The Cox regression analysis included risk score and clinicopathological factors to determine whether risk score was an independent risk factor. Models based on genes associated with fatty acid metabolism were evaluated using receiver operating characteristic curves. A comparison was made between risk score levels and the fatty acid metabolism-associated genes in different subtypes of breast cancer. The differential gene sets of the Kyoto Encyclopedia of Genes and Genomes for screening high- and low-risk populations were compared using a gene set enrichment analysis. Furthermore, we utilized CIBERSORT to examine the abundance of immune cells in breast cancer in different clustering models.Results: High expression levels of ALDH1A1 and UBE2L6 prevented breast cancer, whereas high RDH16 expression levels increased its risk. Our comprehensive assessment of the association between prognostic risk scoring models and tumor microenvironment characteristics showed significant differences in the abundance of various immune cells between high- and low-risk breast cancer patients.Conclusions: By assessing fatty acid metabolism patterns, we gained a better understanding of the infiltration characteristics of the tumor microenvironment. Our findings are valuable for prognosis prediction and treatment of patients with breast cancer based on their clinicopathological characteristics.

Integrins are closely related to the occurrence and development of tumors. ITGA8 encodes the alpha 8 subunit of the heterodimeric integrin alpha8beta1. Studies on the role of this gene in the occurrence and development of lung cancer are scarce. The examination of public databases revealed that ITGA8 expression was significantly lower in tumor tissue than that in normal tissue, especially in lung cancer, renal carcinoma, and prostate cancer. Survival analysis of patients with lung adenocarcinoma revealed that higher ITGA8 expression had better prognosis. ITGA8 was positively related to immune checkpoints and immunomodulators, whereas B cell, CD4+ T cell, CD8+ T cell, neutrophil, macrophage, and dendritic cell infiltration had the same correlation. Moreover, ITGA8 was negatively related to cancer stemness. We used an online database to predict the miRNAs and lncRNAs that regulate ITGA8 and obtained the regulatory network of ITGA8 through correlation analysis and Kaplan–Meier survival analysis. Quantitative real-time PCR and western blot analyses showed that LINC01798 regulates ITGA8 expression through miR-17-5p. Therefore, the regulatory network of ITGA8 may serve as a new therapeutic target to improve the prognosis of patients with lung cancer.

BackgroundWith the ongoing push to improve the quality of talent in all professions, academic pressure on undergraduates is gradually increasing, leading to students feeling increasingly frustrated by academic stressors. As it becomes more widespread, the resulting issue of academic frustration is attracting public attention.AimThe current study explored the relationship between undergraduate anti-frustration ability (AFA) on their academic frustration (AF), focusing specifically on the roles played by core competence (CC) and coping style (CS) in this relationship.MethodsOur sample comprised 1,500 undergraduate students from universities in China. Data collection made use of the Ability to Anti-Frustration Ability Questionnaire, the Academic Frustration Questionnaire, the Core Competence Questionnaire, and the Simple Coping Style Questionnaire.ResultsThe results showed that: (1) AFA negatively predicted the AF of undergraduates, with CC mediating this relationship and (2) CS had a moderating effect on the relationship between CC and AF. We concluded that students who employ positive CS may be more successful in alleviating their AF to a larger extent, with the mediation of CC.InterpretationThe results revealed the mechanism of AFA on AF, which will help schools consider and guide students’ skills and abilities, both academically and personally.

By drawing on a case study of three Chinese novice teachers, this article illustrates that social networking technologies create opportunities for teachers to establish links with parents, allowing direct and prolonged interaction. This has constructed an arena for novice teachers to venture into and navigate through with continual negotiation between their selves and the parents. This process may involve the enactment of particular notions of the professional role, such as messenger, problem-solver and community liaison. These notions reflect different understandings of and responsibilities to students and parents, and differing perspectives on and usage of SNS tools. This study sheds new light on the complexity of novice teachers’ identity formation in the context of a social life that is deeply entwined with social networking technologies. It also speaks to the need to prepare pre-service teachers for establishing and sustaining a relationship with parents, taking into account the mediating role of social networking sites.

WEE1 has emerged as an attractive target in epithelial ovarian cancer (EOC), but how EOC cells may alter their sensitivity to WEE1 inhibition remains unclear. Here, through a cell cycle machinery–related gene RNAi screen, we found that targeting outer dense fiber of sperm tails 2–like (ODF2L) was a synthetic lethal partner with WEE1 kinase inhibition in EOC cells. Knockdown of ODF2L robustly sensitized cells to treatment with the WEE1 inhibitor AZD1775 in EOC cell lines in vitro as well as in xenografts in vivo. Mechanistically, the increased sensitivity to WEE1 inhibition upon ODF2L loss was accompanied by accumulated DNA damage. ODF2L licensed the recruitment of PKMYT1, a functionally redundant kinase of WEE1, to the CDK1–cyclin B complex and thus restricted the activity of CDK1 when WEE1 was inhibited. Clinically, upregulation of ODF2L correlated with CDK1 activity, DNA damage levels, and sensitivity to WEE1 inhibition in patient-derived EOC cells. Moreover, ODF2L levels predicted the response to WEE1 inhibition in an EOC patient–derived xenograft model. Combination treatment with tumor-targeted lipid nanoparticles that packaged ODF2L siRNA and AZD1775 led to the synergistic attenuation of tumor growth in the ID8 ovarian cancer syngeneic mouse model. These data suggest that WEE1 inhibition is a promising precision therapeutic strategy for EOC cells expressing low levels of ODF2L.

Multipotent mesenchymal stromal cells (MSCs) expand in vitro and undergo replicative senescence, thereby restricting their clinical utilization. Thus, an effective strategy is required to impede MSC senescence. Since spermidine (SPD) supplementation can prolong the lifespan of yeast by inhibiting oxidative stress, spermidine is a potential option for delaying MSC senescence. In this study, to test our hypothesis, we first isolated primary human umbilical cord mesenchymal stem cells (hUCMSCs). Subsequently, the appropriate SPD dose was administered during continuous cell cultivation. Next, we evaluated the antisenescence effects by SA-β-gal staining, Ki67 expression, reactive oxygen species (ROS) levels, adipogenic or osteogenic ability, senescence-associated markers, and DNA damage markers. The results revealed that early SPD intervention significantly delays the replicative senescence of hUCMSCs and constrains premature H2O2-induced senescence. Additionally, by silencing SIRT3, the SPD-mediated antisenescence effects disappear, further demonstrating that SIRT3 is necessary for SPD to exert its antisenescence effects on hUCMSCs. Besides, the findings of this study also suggest that SPD in vivo protects MSCs against oxidative stress and delays cell senescence. Thus, MSCs maintain the ability to proliferate and differentiate efficiently in vitro and in vivo, which reflects the potential clinical utilization of MSCs in the future.

WD-repeat protein 72WDR72;OMIM∗613214, a scaffolding protein lacking intrinsic enzymatic activity, produces numerous β-propeller blade formations, serves as a binding platform to assemble protein complexes and is critical for cell growth, differentiation, adhesion, and migration. Despite evidence supporting a basic role of WDR72 in the tumorigenesis of particular cancers, the value of WDR72 in non-small-cell lung cancer (NSCLC), the tumor with the highest mortality rate globally, is undocumented. We investigated the prognostic value of WDR72 in NSCLC and studied its potential immune function and its correlation with ferroptosis. According to The Cancer Genome Atlas, Cancer Cell Line Encyclopedia, Genotype-Tissue Expression, and Gene Set Cancer Analysis, we used multiple bioinformatic strategies to investigate the possible oncogenic role of WDR72, analyze WDR72 and prognosis, and immune cell infiltration in different tumors correlation. WDR72 exhibited a high expression in NSCLC and a positive association with prognosis. WDR72 expression was related to immune cell infiltration and tumor immune microenvironment in NSCLC. Finally, we validated WDR72 in human NSCLC; it has a predictive value in NSCLC related to its function in tumor progression and immunity. The significance of our study is that WDR72 can be used as a potential indicator of lung cancer prognosis. Helping physicians more accurately predict patient survival and risk of disease progression.

Objective To explore the clinical value of autoantibody-based subgroup framework and the trend of autoantibody fluctuation in juvenile-onset SLE (JSLE).Methods Eighty-seven patients with JSLE were retrospectively collected and divided into subgroups via a two-step cluster based on the status of nine autoantibodies (double-stranded-DNA (dsDNA), nucleosome, histone, ribosomal P protein, Smith (Sm), u1-ribonucleoprotein (RNP), Sjögren’s syndrome antigen A (SSA)/Ro52, SSA/Ro60, Sjögren’s syndrome antigen B (SSB)/La). The final model selected in this study was based on adequate goodness of fit of the Silhouette coefficient and clinical interpretability. Clinical manifestations, organ involvements and disease activity were compared among the subgroups. Fluctuation in autoantibody status was also collected and analysed. Flare-free survival rates of the patients with positive/negative seroconversion and patients without seroconversion were studied by the Kaplan-Meier method and compared using a log-rank test.Results Two clusters were identified: subgroup 1 (positive anti-Sm/RNP group) and subgroup 2 (negative anti-Sm/RNP group). There were more lupus nephritis (LN) and neuropsychiatric SLE (NPSLE) cases in subgroup 1 than in subgroup 2. Patients in subgroup 1 exhibited higher SLE Disease Activity Index scores compared with those in subgroup 2. Furthermore, anti-ribosomal P protein (61.1%), anti-nucleosome (58.3%) and anti-dsDNA (54%) were most commonly positive autoantibodies. A progressive decrease in the frequency of patients with positive results was demonstrated during the follow-up years. The decrease was notable for anti-dsDNA, anti-nucleosome and anti-ribosomal P protein (remaining 27.27%, 38.89% and 45.00% positive in the fifth year, respectively). While for those negative at baseline diagnosis, the decrease in the frequency of negative results was progressive but modest. Kaplan-Meier curve showed that the flare-free survival of patients with positive seroconversion was significantly lower than those without seroconversion and those with negative seroconversion (p

Capping protein regulator and myosin 1 linker 2 (CARMIL2) is necessary for invadopodia formation, cell polarity, lamellipodial assembly, membrane ruffling, acropinocytosis, and collective cell migration. CARMIL2 deficiency is a rare autosomal recessive disease characterized by dysfunction in naïve T-cell activation, proliferation, differentiation, and effector function and insufficient responses in T-cell memory. In this paper, we report a 9-year-old female patient with a novel pathogenic variant in CARMIL2 (c.2063C > G:p.Thr688Arg) who presented with various symptoms of primary immunodeficiencies including recurrent upper and lower respiratory infections, perioral and perineum papules, reddish impetiginized atopic dermatitis, oral ulcer, painful urination and vaginitis, otitis media, and failure to thrive. A missense mutation leading to insufficient CARMIL2 protein expression, reduced absolute T-cell and natural killer cell (NK cell) counts, and marked skewing to the naïve T-cell form was identified and indicated defective maturation of T cells and B cells. Following 1 year of multitargeted treatment with corticosteroids, hydroxychloroquine, mycophenolate mofetil, and thymosin, the patient presented with significant regression in rashes. CD4+ T-cell, CD8+ T-cell, and NK cell counts were significantly improved.

Radiotherapy is one of the mainstays of cancer treatment. More than half of cancer patients receive radiation therapy. In addition to the well-known direct tumoricidal effect, radiotherapy has immunomodulatory properties. When combined with immunotherapy, radiotherapy, especially high-dose radiotherapy (HDRT), exert superior systemic effects on distal and unirradiated tumors, which is called abscopal effect. However, these effects are not always effective for cancer patients. Therefore, many studies have focused on exploring the optimized radiotherapy regimens to further enhance the antitumor immunity of HDRT and reduce its immunosuppressive effect. Several studies have shown that low-dose radiotherapy (LDRT) can effectively reprogram the tumor microenvironment, thereby potentially overcoming the immunosuppressive stroma induced by HDRT. However, bridging the gap between preclinical commitment and effective clinical delivery is challenging. In this review, we summarized the existing studies supporting the combined use of HDRT and LDRT to synergistically enhance antitumor immunity, and provided ideas for the individualized clinical application of multimodal radiotherapy (HDRT+LDRT) combined with immunotherapy.

IntroductionIn confronting the sudden COVID-19 epidemic, China and other countries have been under great pressure to block virus transmission and reduce fatalities. Converting large-scale public venues into makeshift hospitals is a popular response. This addresses the outbreak and can maintain smooth operation of a country or region's healthcare system during a pandemic. However, large makeshift hospitals, such as the Shanghai New International Expo Center (SNIEC) makeshift hospital, which was one of the largest makeshift hospitals in the world, face two major problems: Effective and precise transfer of patients and heterogeneity of the medical care teams.MethodsTo solve these problems, this study presents the medical practices of the SNIEC makeshift hospital in Shanghai, China. The experiences include constructing two groups, developing a medical management protocol, implementing a multi-dimensional management mode to screen patients, transferring them effectively, and achieving homogeneous quality of medical care. To evaluate the medical practice performance of the SNIEC makeshift hospital, 41,941 infected patients were retrospectively reviewed from March 31 to May 23, 2022. Multivariate logistic regression method and a tree-augmented naive (TAN) Bayesian network mode were used.ResultsWe identified that the three most important variables were chronic disease, age, and type of cabin, with importance values of 0.63, 0.15, and 0.11, respectively. The constructed TAN Bayesian network model had good predictive values; the overall correct rates of the model-training dataset partition and test dataset partition were 99.19 and 99.05%, respectively, and the respective values for the area under the receiver operating characteristic curve were 0.939 and 0.957.ConclusionThe medical practice in the SNIEC makeshift hospital was implemented well, had good medical care performance, and could be copied worldwide as a practical intervention to fight the epidemic in China and other developing countries.

IntroductionThe initial presentations of childhood-onset primary Sjögren’s syndrome (C-pSS) vary, making diagnosis challenging. We aimed to improve the diagnosis and evaluation of C-pSS by summarizing its clinical and laboratory features.MethodsA total of 49 patients with C-pSS between July 2015 and August 2022 in the Department of Rheumatology and Immunology of Shanghai Children's Medical Centre were enrolled in this study. Their clinical manifestations and laboratory examinations of these patients were compared based on the presence or absence of thrombocytopenia and parotitis and whether the immunological markers, including anti-nuclear antibodies (ANA), rheumatoid factor (RF), anti-Ro52/SSA antibodies (anti-SSA/Ro52), anti-Ro60/SSA antibodies (anti-SSA/Ro60), and anti-Ro/SSB antibodies (anti-SSB), were positive.ResultsThe mean age at C-pSS diagnosis was 10.34 ± 3.45 years, and the ratio of boys to girls was 1:6. In the thrombocytopenia group, parotitis (P = 0.044), organ involvement except for hematology (P = 0.002), positive anti-SSB (P = 0.004), and positive RF (P = 0.001) were less frequently observed. Complement C4 (P = 0.038) and white blood cells (P = 0.002) levels decreased and increased significantly, respectively. Anti-SSB (P = 0.010) and RF (P = 0.004) positivity were independent potential protective factors against thrombocytopenia in patients with C-pSS. In the parotitis group, higher ANA titers (P = 0.027), higher focus scores on labial gland biopsy (P = 0.024), and positive RF (P = 0.001), anti-SSA/Ro60 (P = 0.003), and anti-SSB (P = 0.001) were observed more frequently. Furthermore, positive anti-SSB (P = 0.012) and positive RF (P = 0.028) were independent risk factors for parotitis in patients with C-pSS. The hemoglobin level was significantly lower in patients with positive anti-SSA/Ro52 and positive anti-SSA/Ro60 results (P = 0.022 and P = 0.029, respectively), while immunoglobulin G level was significantly higher in patients in the same group (P = 0.048 and P = 0.007, respectively).ConclusionsPositive anti-SSB and positive RF values may be independent potential protective factors of thrombocytopenia in patients with C-pSS. In contrast, positive anti-SSB and positive RF were independent risk factors of parotitis in patients with C-pSS. More studies are needed to reveal the diagnostic role and pathogenic mechanism of immunological markers in C-pSS.

The onset of prostate cancer (PCa) is often hidden, and recurrence and metastasis are more likely to occur due to chemotherapy resistance. Herein, we identified downregulated long noncoding RNA (lncRNA) growth arrest-specific 5 (GAS5) in PCa that was associated with metastasis and paclitaxel resistance. GAS5 acted as a tumor suppressor in suppressing the proliferation and metastasis of paclitaxel-resistant PCa cells. GAS5 overexpression in vivo inhibited the tumor growth of xenografts and elevated PCa sensitivity to paclitaxel. Combination of GAS5 and paclitaxel treatment showed great potential in PCa treatment. Moreover, mechanistic analysis revealed a novel regulatory network of GAS5/miR-18a-5p/serine/threonine kinase 4 (STK4) that inhibits epithelial-to-mesenchymal transition (EMT) and enhances tumor stem cell-like-mediated sensitivity to paclitaxel in PCa. These findings provide a novel direction for the development of a potential adjunct to cancer chemotherapy that aims to improve the sensitivity of chemotherapy drugs in PCa.

Abstract Background Patients with non‐small cell lung cancer (NSCLC) are diagnosed in advanced stages and with a poor 5‐year survival rate. There is a critical need to identify novel biomarkers to improve the therapy and overall prognosis of this disease. Methods Differentially expressed genes (DEGs) were identified from three profiles of GSE101586, GSE101684 and GSE112214 using Venn diagrams. hsa_circ_0043256 were validated using quantitative real‐time polymerase chain reaction (RT‐qPCR). The circular RNA–microRNA–messenger RNA (circRNA–miRNA–mRNA) regulatory network was constructed with Cytoscape 3.7.0. Hub genes were identified with protein interaction (PPI) and validated with the Gene Expression Profiling Interactive Analysis (GEPIA), Human Protein Atlas (HPA) databases, and immunohistochemistry. Survival analyses were also performed using a Kaplan–Meier (KM) plotter. The effects of hsa_circ_0043256 on cell proliferation and cell cycles were evaluated by EdU staining and flow cytometry, respectively. Results hsa_circ_0043256, hsa_circ_0029426 and hsa_circ_0049271 were obtained. Following RT‐qPCR validation, hsa_circ_0043256 was selected for further analysis. In addition, functional experiment results indicated that hsa_circ_0043256 could inhibit cell proliferation and cell‐cycle progression of NSCLC cells in vitro. Prediction by three online databases and combining with DEGs identified from The Cancer Genome Atlas (TCGA), a network containing one circRNAs, three miRNAs, and 209 mRNAs was developed. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis indicated DEGs might be associated with lung cancer onset and progression. A PPI network based on the 209 genes was established, and five hub genes (BIRC5, SHCBP1, CCNA2, SKA3, and GINS1) were determined. Following verification of five hub genes using GEPIA database, HPA database, and immunohistochemistry. High expression of all five hub genes led to poor overall survival. Conclusion Our study constructed a circRNA–miRNA–mRNA network of hsa_circ_0043256. hsa_circ_0043256 may be a potential therapeutic target for lung cancer.

Abstract. The emergence and spread of plasmid-mediated tigecycline resistance genes have attracted extensive attention worldwide. We investigated the distribution of mobile tigecycline resistance genes in Salmonella genomes generated by both our laboratory and public bacterial genomes downloaded from the NCBI GenBank. The tet(X4)-positive strains were subjected to susceptibility testing and conjugation assays. The genetic features of the tet(X4)-bearing plasmid sequence were analyzed. Here, we report the identification of the plasmid-mediated tigecycline resistance gene tet(X4) in a conjugative plasmid of the Salmonella enterica serovar Llandoff strain SH16G3606, isolated from a man in China in 2016, the first reported serovar Llandoff in China as a novel sequence type ST8300. The tet(X4)-mediated resistance phenotype was successfully transferred from the Salmonella Llandoff strain into Escherichia coli J53, resulting in a 32-fold increase in the minimal inhibitory concentration of tigecycline. The tet(X4) gene was located between two copies of ISCR2 in the plasmid pSal21GXH-tetX4. To our knowledge, this is the first report of the plasmid-mediated tigecycline resistance gene tet(X4) in a Salmonella Llandoff strain isolated from a human stool sample in China. In addition, our findings demonstrated that a total of 171 isolates are carrying tet(X)-like genes distributed in 21 countries or areas across 6 continents, posing a serious threat to humans and public health. Overall, our timely discovery of the recent emergence of the tet(X4) gene in Salmonella isolates and other Enterobacteriaceae bacteria species supports the need for rapid surveillance to prevent the tet(X)-like gene from spreading.

Abstract Background Angiogenesis plays an important role in the occurrence, development and metastasis of hepatocellular carcinoma (HCC). According to previous studies, miR-378a participates in tumorigenesis and tumor metastasis, but its exact role in HCC angiogenesis remains poorly understood. Methods qRT-PCR was used to investigate the expression of miR-378a-3p in HCC tissues and cell lines. The effects of miR-378a-3p on HCC in vitro and in vivo were examined by Cell Counting Kit-8 (CCK-8), Transwell, tube formation and Matrigel plug assays, RNA sequencing, bioinformatics, luciferase reporter, immunofluorescence and chromatin immunoprecipitation (ChIP) assays were used to detect the molecular mechanism by which miR-378a-3p inhibits angiogenesis. Results We confirmed that miR-378a-3p expression was significantly downregulated and associated with higher microvascular density (MVD) in HCC; miR-378a-3p downregulation indicated a short survival time in HCC patients. miR-378a-3p knockdown led to a significant increase in angiogenesis in vitro and in vivo. We found that miR-378a-3p directly targeted TNF receptor associated factor 1 (TRAF1) to attenuate NF-κB signaling, and then downregulated secreted vascular endothelial growth factor. DNA methyltransferase 1 (DNMT1)-mediated hypermethylation of miR-378a-3p was responsible for downregulating miR-378a-3p. Moreover, a series of investigations indicated that p65 initiated a positive feedback loop that could upregulate DNMT1 to promote hypermethylation of the miR-378a-3p promoter. Conclusion Our study indicates a novel DNMT1/miR-378a-3p/TRAF1/NF-κB positive feedback loop in HCC cells, which may become a potential therapeutic target for HCC.

Interconnectivity is the key characteristic of bone tissue engineering scaffold modulating cell migration, blood vessels invasion and transport of nutrient and waste. However, efforts and understanding of the interconnectivity of porous Mg is limited due to the diverse architectures of pore struts and pore size distribution of Mg scaffold systems. In this work, biomimetic hierarchical porous Mg scaffolds with tailored interconnectivity as well as pore size distribution were prepared by template replication of infiltration casting. Mg scaffold with better interconnectivity showed lower mechanical strength. Enlarging interconnected pores would enhance the interconnectivity of the whole scaffold and reduce the change of ion concentration, pH value and osmolality of the degradation microenvironment due to the lower specific surface area. Nevertheless, the degradation rates of five tested Mg scaffolds were no different because of the same geometry of strut unit. Direct cell culture and evaluation of cell density at both sides of four typical Mg scaffolds indicated that cell migration through hierarchical porous Mg scaffolds could be enhanced by not only bigger interconnected pore size but also larger main pore size. In summary, design of interconnectivity in terms of pore size distribution could regulate mechanical strength, microenvironment in cell culture condition and cell migration potential, and beyond that it shows great potential for personalized therapy which could facilitate the regeneration process.

Abstract Background The present study performed two distinct meta-analyses with common outcomes (sperm parameters); one was performed in obese individuals (and non-obese controls) and the other in diabetic individuals (and non-diabetic controls). Methods PubMed, Embase, The Cochrane library, Web of Science, Scopus databases were searched to collect clinical studies related to the effects of obesity and diabetes on male sperm from inception to on 1st February 2021. Statistical meta-analyses were performed using the RevMan 5.4 software. Stata16 software was used to detect publication bias. The methodological quality of the included studies was assessed with the Ottawa–Newcastle scale using a star-based system. Results A total of 44 studies were finally included in the present study, which enrolled 20,367 obese patients and 1386 patients with diabetes. The meta-analysis results showed that both obesity and diabetes were associated with reduced semen volume (obese versus non-obese controls: mean difference (MD) = − 0.25, 95% CI = (− 0.33, − 0.16), p < 0.001; diabetes versus non-diabetic controls: MD = − 0.45, 95% CI = (− 0.63, − 0.27), p < 0.001), reduced sperm count (obese versus non-obese controls: MD = − 23.84, 95% CI = (− 30.36, − 17.33), p < 0.001; diabetes versus non-diabetic controls: MD = − 13.12, 95% CI = (− 18.43, − 7.82), p < 0.001), reduced sperm concentration (obese versus non-obese controls: MD = − 7.26, 95% CI = (− 10.07, − 4.46), p < 0.001; diabetes versus non-diabetic controls: MD = − 11.73, 95% CI = (− 21.44, − 2.01), p = 0.02), reduced progressive motility (obese versus non-obese controls: MD = − 5.68, 95% CI = (− 8.79, − 2.56), p < 0.001; diabetes versus non-diabetic controls: MD = − 14.37, 95% CI = (− 21.79, − 6.96), p = 0.001), and decreased testosterone levels (obese versus non-obese controls: MD = − 1.11, 95% CI = (− 1.92, − 0.30), p = 0.007; diabetes versus non-diabetic controls: MD = − 0.37, 95% CI = (− 0.63, − 0.12), p = 0.004). Conclusions Current evidence suggests that obesity and diabetes negatively affect sperm parameters in men and are associated with low testosterone levels. Due to the limitation of the number and quality of included studies, the above conclusions need to be verified by more high-quality studies.

BackgroundThe tumor necrosis factor (TNF) family plays a role in modulating cellular functions that regulate cellular differentiation, survival, apoptosis, and especially cellular immune functions. The TNF family members also play important roles in oncogenesis and progression. However, the potential role of the TNF family members in lung adenocarcinoma (LUAD) is yet to be explored.MethodsThe expression of TNF-related genes (TNFRGs) in 1,093 LUAD samples was investigated using The Cancer Genome Atlas and Gene Expression Omnibus datasets. The characteristic patterns of TNFRGs in LUAD were systematically probed and three distinct molecular subtypes were identified. Furthermore, a correlation was found between the different subtypes and their clinical characteristics. A TNF scoring system was created to predict overall survival (OS) and therapeutic responses in patients with LUAD. Subsequently, the predictive accuracy of the score was verified and a nomogram was used to optimize the clinical applicability range of the TNF score.ResultsA high TNF score, involving the immune and stromal scores, indicated negative odds of OS. Moreover, the TNF score was associated with immune checkpoints and chemotherapeutic drug sensitivity. Collectively, our comprehensive TNFRGs analysis of patients with LUAD revealed that TNF could be involved in forming the diverse and complex tumor microenvironment, its clinicopathological features, and its prognosis.ConclusionsA TNF-related prognostic model was constructed, and a TNF score was developed. These findings are expected to improve our knowledge regarding the function of TNFRGs in LUAD, pave a new path for assessing the disease prognosis, and assist in developing personalized therapeutic strategies for patients with LUAD.

Although RAD51 associated protein 1 (RAD51AP1) is crucial in genome stability maintenance, it also promotes cancer development with an unclear mechanism. In this study, we collected intact expression data of RAD51AP1 from the public database, and verified it was significantly over-expressed in 33 cancer types and correlated with poor prognosis in 13 cancer types, including glioma, adrenocortical carcinoma, lung adenocarcinoma. We further authenticated that RAD51AP1 is up-regulated in several typical cancer cell lines and promotes cancer cell proliferation in vitro. Moreover, we also demonstrated that RAD51AP1 was significantly positively related to cancer stemness score mRNAsi in 27 cancer types and broadly correlated to tumor-infiltrating immune cells in various cancers in a diverse manner. It was also negatively associated with immunophenoscore (IPS) and Estimation of STromal and Immune cells in MAlignant Tumours using Expression data (ESTIMATE) scores and positively correlated with mutant-allele tumor heterogeneity (MATH), tumor mutational burden (TMB), microsatellite instability (MSI), and PD-L1 expression in multiple cancers. The tumor stemness enhancing and tumor immune microenvironment affecting functions of RAD51AP1 might compose its carcinogenesis mechanism. Further investigations beyond the bioinformatics level should confirm these findings in each specific cancer.

Polycystic ovary syndrome (PCOS) is a lifelong reproductive, metabolic, and psychiatric disorder that affects 5-18% of women, which is associated with a significantly increased lifetime risk of concomitant diseases, including type 2 diabetes, psychiatric disorders, and gynecological cancers. Posttranslational modifications (PTMs) play an important role in changes in protein function and are necessary to maintain cellular viability and biological processes, thus their maladjustment can lead to disease. Growing evidence suggests the association between PCOS and posttranslational modifications. This article mainly reviews the research status of phosphorylation, methylation, acetylation, and ubiquitination, as well as their roles and molecular mechanisms in the development of PCOS. In addition, we briefly summarize research and clinical trials of PCOS therapy to advance our understanding of agents that can be used to target phosphorylated, methylated, acetylated, and ubiquitinated PTM types. It provides not only ideas for future research on the mechanism of PCOS but also ideas for PCOS treatments with therapeutic potential.