Unraveling resistance mechanisms in anti-CD19 chimeric antigen receptor-T therapy for B-ALL: a novel in vitro model and insights into target antigen dynamics.

BACKGROUND: Cellular immunotherapy, represented by the chimeric antigen receptor T cell (CAR-T), has exhibited high response rates, durable remission, and safety in vitro and in clinical trials. Unfortunately, anti-CD19 CAR-T (CART-19) treatment alone is prone to relapse and has a particularly poor prognosis in relapsed/refractory (r/r) B-ALL patients. To date, addressing or reducing relapse remains one of the research priorities to achieve broad clinical application. METHODS: We manufactured second generation CART-19 cells and validated their efficacy and safety in vitro and in vivo. Through co-culture of Nalm-6 cells with short-term cultured CART-19 cells, CD19-negative Nalm-6 cells were detected by flow cytometry, and further investigation of the relapsed cells and their resistance mechanisms was evaluated in vitro. RESULTS: In this study, we demonstrated that CART-19 cells had enhanced and specific antileukemic activities, and the survival of B-ALL mouse models after CART-19 treatment was significantly prolonged. We then shortened the culture time and applied the serum-free culture to expand CAR-T cells, followed by co-culturing CART-19 cells with Nalm-6 cells. Surprisingly, we observed the proliferation of CD19-negative Nalm-6 cells around 28 days. Identification of potential resistance mechanisms showed that the relapsed cells express truncated CD19 proteins with decreased levels and, more importantly, CAR expression was detected on the relapsed cell surface, which may ultimately keep them antigen-negative. Furthermore, it was validated that CART-22 and tandem CART-22/19 cells could effectively kill the relapsed cells, but neither could completely eradicate them. CONCLUSIONS: We successfully generated CART-19 cells and obtained a CD19-negative refractory relapsed B-ALL cell line, providing new insights into the underlying mechanisms of resistance and a new in vitro model for the treatment of r/r B-ALL patients with low antigen density.

Thoracolumbar fractures patients undergoing posterior pedicle screw fixation can benefit from drainage.

PURPOSE: To explore whether it is necessary to put drain tubes after posterior pedicle screw fixation of thoracolumbar fractures. METHODS: From April 2020 to January 2023, a total of 291 patients with recent thoracolumbar fractures (AO type-A or type-B) who received the pedicle screw fixation operation were enrolled retrospectively. In 77 patients, drain tubes were used in the pedicle screw fixation surgery, while no drain tubes were placed in the other group. After gleaning demographic information and results of lab examination and imageology examination, all data were put into a database. Independent-sample t-tests, Pearson Chi-Square tests, Linear regression analysis, and correlation analysis were then performed. RESULTS: Compared to the control group, the drainage group had significantly lower postoperative CRP levels (P = 0.047), less use of antipyretics (P = 0.035), higher ADL scores (P = 0.001), and lower NRS scores (P < 0.001) on the 6th day after surgery. Other investigation items, such as demographic information, operation time, intraoperative blood loss, body temperature, and other preoperative and postoperative lab results, showed no significant differences. CONCLUSIONS: The use of a drain tube in the pedicle screw fixation of thoracolumbar fractures is correlated with the improvement of patients' living and activity ability and the reduction of inflammation, postoperative fever and pain.

Prediction of the Effects of Pulsating Hydraulic Fracturing on the Porous Structure and Permeability of Coal Based on NMR and AE Spectra.

Pulsating hydraulic fracturing has been an environmentally friendly method to improve the permeability of rock formations to stimulate gas production and reduce hazard risks. It has the advantage of fracturing the reservoir with lower cracking pressure and less water volume, as the mechanical strength of rock materials has been reduced by the hydraulic pulse pressure. Many researchers have found significant changes in hard rocks after cyclic loading. However, the existing work still cannot clearly explain the mechanism of the rock damage by pulsating hydraulic fracturing within a short-time experiment. To solve the issue, an investigation of the effects of pulsating hydraulic fracturing on CBM production has been carried out in lab and field applications. Results indicate that the long-term hydraulic pulse pressure can cause a linear decline in cracking pressure directly measured in the lab. It plays an essential role in the permeability enhancement by generating more flow channels for CBM production. The low-field NMR quantitatively evaluates the increase in porosity, which reveals significant incremental ratios of over 20% in the porosity of macropores, mesopores, and micropores of coal caused by fatigue damage. It is first proven that hydraulic pulse pressure has a significant influence on the porosity components of macropores, mesopores, and micropores. To validate the effectiveness of the technique on the field scale, a field application of pulsating hydraulic fracturing has been carried out in a coal mine. It shows that gas production has been largely enhanced with a long and stable production stage and higher gas flux after the applied pulsating load. The gas concentration and gas flux of the fractured boreholes are about 2 times that of the nonfractured boreholes. This work provides an investigation of the effects of pulsating hydraulic fracturing on CBM production, which gives a better understanding of the mechanism for the engineers in the field.

Discriminative diagnosis of ovarian endometriosis cysts and benign mucinous cystadenomas based on the ConvNeXt algorithm.

PURPOSE: The objective of this study was to develop a deep learning model, using the ConvNeXt algorithm, that can effectively differentiate between ovarian endometriosis cysts (OEC) and benign mucinous cystadenomas (MC) by analyzing ultrasound images. The performance of the model in the diagnostic differentiation of these two conditions was also evaluated. METHODS: A retrospective analysis was conducted on OEC and MC patients who had sought medical attention at the Fourth Affiliated Hospital of Harbin Medical University between August 2018 and May 2023. The diagnosis was established based on postoperative pathology or the characteristics of aspirated fluid guided by ultrasound, serving as the gold standard. Ultrasound images were collected and subjected to screening and preprocessing procedures. The data set was randomly divided into training, validation, and testing sets in a ratio of 5:3:2. Transfer learning was utilized to determine the initial weights of the ConvNeXt deep learning algorithm, which were further adjusted by retraining the algorithm using the training and validation ultrasound images to establish a new deep learning model. The weights that yielded the highest accuracy were selected to evaluate the diagnostic performance of the model using the validation set. Receiver operating characteristic (ROC) curves were generated, and the area under the curve (AUC) was calculated. Additionally, sensitivity, specificity, positive predictive value, negative predictive value, positive likelihood ratio, negative likelihood ratio, and odds ratio were calculated. Decision curve analysis (DCA) curves were plotted. RESULTS: The study included 786 ultrasound images from 184 patients diagnosed with either OEC or MC. The deep learning model achieved an AUC of 0.90 (95 % CI: 0.85-0.95) in accurately distinguishing between the two conditions, with a sensitivity of 90 % (95 % CI: 84 %-95 %), specificity of 90 % (95 % CI: 77 %-97 %), a positive predictive value of 96 % (95 % CI: 91 %-99 %), a negative predictive value of 77 % (95 % CI: 63 %-88 %), a positive likelihood ratio of 9.27 (95 % CI: 3.65-23.56), and a negative likelihood ratio of 0.11 (95 % CI: 0.06-0.19). The DCA curve demonstrated the practical clinical utility of the model. CONCLUSIONS: The deep learning model developed using the ConvNeXt algorithm exhibits high accuracy (90 %) in distinguishing between OEC and MC. This model demonstrates excellent diagnostic performance and clinical utility, providing a novel approach for the clinical differentiation of these two conditions.

4-Octyl Itaconate Attenuates Neuroinflammation in Experimental Autoimmune Encephalomyelitis Via Regulating Microglia.

Abnormal activation of microglia, the resident macrophages in the central nervous system, plays an important role in the pathogenesis of multiple sclerosis (MS). The immune responsive gene 1(IRG1)/itaconate axis is involved in regulating microglia-mediated neuroinflammation. 4-Octyl itaconate (4-OI), a derivative of itaconate, plays a crucial immunomodulatory role in macrophages. This study investigated the effects and mechanisms of action of 4-OI on experimental autoimmune encephalomyelitis (EAE) and inflammatory BV2 microglia. In an EAE mouse model, clinical evaluation was conducted during the disease course. Hematoxylin and eosin staining was performed to assess inflammatory infiltration and Luxol Fast Blue was used to visualize pathological damage. Quantitative real-time polymerase chain reaction, western blotting and immunofluorescence were used to evaluate inflammatory response and microglial function status in EAE mice. BV2 microglia were used to further investigate the effects and mechanisms of action of 4-OI in vitro. 4-OI significantly alleviated the clinical symptoms of EAE, the inflammatory infiltration, and demyelination; reduced the levels of inflammatory factors; and inhibited the classical activation of microglia in the spinal cord. 4-OI successfully suppressed the classical activation of BV2 microglia and decreased the levels of inflammatory factors by activating the Nrf2/HO-1 signaling pathway. Furthermore, 4-OI downregulated IRG1 expression in both EAE mice and inflammatory BV2 microglia. 4-OI attenuates the microglia-mediated neuroinflammation and has promising therapeutic effects in MS.

Multimodal analysis of cfDNA methylomes for early detecting esophageal squamous cell carcinoma and precancerous lesions.

Detecting early-stage esophageal squamous cell carcinoma (ESCC) and precancerous lesions is critical for improving survival. Here, we conduct whole-genome bisulfite sequencing (WGBS) on 460 cfDNA samples from patients with non-metastatic ESCC or precancerous lesions and matched healthy controls. We develop an expanded multimodal analysis (EMMA) framework to simultaneously identify cfDNA methylation, copy number variants (CNVs), and fragmentation markers in cfDNA WGBS data. cfDNA methylation markers are the earliest and most sensitive, detectable in 70% of ESCCs and 50% of precancerous lesions, and associated with molecular subtypes and tumor microenvironments. CNVs and fragmentation features show high specificity but are linked to late-stage disease. EMMA significantly improves detection rates, increasing AUCs from 0.90 to 0.99, and detects 87% of ESCCs and 62% of precancerous lesions with >95% specificity in validation cohorts. Our findings demonstrate the potential of multimodal analysis of cfDNA methylome for early detection and monitoring of molecular characteristics in ESCC.

A "twelve-section ultrasonic screening and diagnosis method" and management system for screening and treating neonatal congenital heart disease at the grassroots level in Tang County, Hebei Province, China.

BACKGROUND: To explore a method for screening and diagnosing neonatal congenital heart disease (CHD) applicable to grassroots level, evaluate the prevalence of CHD, and establish a hierarchical management system for CHD screening and treatment at the grassroots level. METHODS: A total of 24,253 newborns born in Tang County between January 2016 and December 2020 were consecutively enrolled and screened by trained primary physicians via the "twelve-section ultrasonic screening and diagnosis method" (referred to as the "twelve-section method"). Specialized staff from the CHD Screening and Diagnosis Center of Hebei Children's Hospital regularly visited the local area for definite diagnosis of CHD in newborns who screened positive. Newborns with CHD were managed according to the hierarchical management system. RESULTS: The centre confirmed that, except for 2 newborns with patent ductus arteriosus missed in the diagnosis of ventricular septal defect combined with severe pulmonary hypertension, newborns with other isolated or concomitant simple CHDs were identified at the grassroots level. The sensitivity, specificity and diagnostic coincidence rate of the twelve-section method for screening complex CHD were 92%, 99.6% and 84%, respectively. A total of 301 children with CHD were identified. The overall CHD prevalence was 12.4‰. According to the hierarchical management system, 113 patients with simple CHD recovered spontaneously during local follow-up, 48 patients continued local follow-up, 106 patients were referred to the centre for surgery (including 17 patients with severe CHD and 89 patients with progressive CHD), 1 patient died without surgery, and 8 patients were lost to follow-up. Eighteen patients with complex CHD were directly referred to the centre for surgery, 3 patients died without surgery, and 4 patients were lost to follow-up. Most patients who received early intervention achieved satisfactory results. The mortality rate of CHD was approximately 28.86 per 100,000 children. CONCLUSIONS: The "twelve-section method" is suitable for screening neonatal CHD at the grassroots level. The establishment of a hierarchical management system for CHD screening and treatment is conducive to the scientific management of CHD, which has important clinical and social significance for early detection, early intervention, reduction in mortality and improvement of the prognosis of complex and severe CHDs.

Design of health information management model for elderly care using an advanced higher-order hybrid clustering algorithm from the perspective of sports and medicine integration.

In the context of integrating sports and medicine domains, the urgent resolution of elderly health supervision requires effective data clustering algorithms. This paper introduces a novel higher-order hybrid clustering algorithm that combines density values and the particle swarm optimization (PSO) algorithm. Initially, the traditional PSO algorithm is enhanced by integrating the Global Evolution Dynamic Model (GEDM) into the Distribution Estimation Algorithm (EDA), constructing a weighted covariance matrix-based GEDM. This adapted PSO algorithm dynamically selects between the Global Evolution Dynamic Model and the standard PSO algorithm to update population information, significantly enhancing convergence speed while mitigating the risk of local optima entrapment. Subsequently, the higher-order hybrid clustering algorithm is formulated based on the density value and the refined PSO algorithm. The PSO clustering algorithm is adopted in the initial clustering phase, culminating in class clusters after a finite number of iterations. These clusters then undergo the application of the density peak search algorithm to identify candidate centroids. The final centroids are determined through a fusion of the initial class clusters and the identified candidate centroids. Results showcase remarkable improvements: achieving 99.13%, 82.22%, and 99.22% for F-measure, recall, and precision on dataset S1, and 75.22%, 64.0%, and 64.4% on dataset CMC. Notably, the proposed algorithm yields a 75.22%, 64.4%, and 64.6% rate on dataset S, significantly surpassing the comparative schemes' performance. Moreover, employing the text vector representation of the LDA topic vector model underscores the efficacy of the higher-order hybrid clustering algorithm in efficiently clustering text information. This innovative approach facilitates swift and accurate clustering of elderly health data from the perspective of sports and medicine integration. It enables the identification of patterns and regularities within the data, facilitating the formulation of personalized health management strategies and addressing latent health concerns among the elderly population.

Evaluating the clinical efficacy and safety of concurrent chemoradiotherapy with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer.

OBJECTIVE: A preclinical study showed that nab-paclitaxel acted as a radiosensitizer and improved tumor radiotherapy in a supra-additive manner. In this study, we aimed to evaluate the clinical efficacy and safety of concurrent chemoradiotherapy (CCRT) with cisplatin and nab-paclitaxel in postoperative early-stage cervical cancer with an unfavorable prognosis. METHODS: Eligible patients with stage IB1-IIA2 (FIGO 2009) cervical carcinoma were recruited retrospectively between August 2018 to May 2021. Patients in both the cisplatin and nab-paclitaxel groups received postoperative radiotherapy and weekly intravenous cisplatin 40 mg/m2 or nab-paclitaxel 100 mg concurrently. An analysis of overall survival, progression-free survival, and adverse reactions was conducted. RESULTS: A total of 105 early-stage cervical cancer patients were included into our study. The median follow-up time was 38.7 months. The 3-year overall survival and progression-free survival in both group was similar. The cycles of chemotherapy in the cisplatin group were less than those in the nab-paclitaxel group (4.5 vs. 5.0; p = 0.001). Patients in the cisplatin group had a significantly higher frequency of hematological adverse events than patients in the nab-paclitaxel group (P < 0.05). Patients in the cisplatin group had a significantly higher frequency of grade 3-4 leukopenia (46.1% vs. 18.9%; P = 0.03), grade 1-2 thrombocytopenia (32.7% vs. 9.5%; P = 0.014) than patients in the nab-paclitaxel group. Gastrointestinal reactions, such as vomiting, nausea, and anorexia were significantly reduced in the nab-paclitaxel group compared with those in the cisplatin group. Regarding the effects on alopecia, the incidence rate of the nab-paclitaxel group was higher than that of the cisplatin group (P = 0.001). There were no differences between the groups in terms of other adverse reactions. CONCLUSION: The results of this study indicate that nab-paclitaxel-based concurrent radiotherapy is tolerable and effective, and can be considered an alternative to cisplatin chemotherapy.

Eco-climate drivers shape virome diversity in a globally invasive tick species.

Spillovers of viruses into human occur more frequently under warmer conditions, particularly arboviruses. The invasive tick species Haemaphysalis longicornis poses a significant public health threat due to its global expansion and its potential to carry a wide range of pathogens. We analyzed meta-transcriptomic data from 3595 adult H. longicornis ticks collected between 2016 and 2019 in 22 provinces across China, encompassing diverse ecological conditions. Generalized additive modelling revealed that climate factors exerted a stronger influence on the virome of H. longicornis compared to other ecological factors, such as ecotypes, distance to coastline, animal host, tick gender, and anti-viral immunity. We investigated the mechanistic understanding of how climate changes drive the tick virome using causality inference and emphasized its significance for public health. Our findings demonstrated that higher temperatures and lower relative humidity/precipitation contribute to variations in animal host diversity, leading to an increased diversity of tick virome, particularly the evenness of vertebrate associated viruses. This finding may explain the evolution of tick-borne viruses into generalists across multiple hosts, thereby increasing the probability of spillover events involving tick-borne pathogens. Deep learning projections indicate that the diversity of H. longicornis virome is expected to increase in 81.9% of regions under the SSP8.5 scenario from 2019-2030. Extension of surveillance should be implemented to avert the spread of tick-borne diseases.

Acacetin alleviates autoimmune myocarditis by regulating CD4+ T cell mitochondrial respiration.

BACKGROUND: Myocarditis refers to an autoimmune inflammatory response of the myocardium with characterization of self-reactive CD4+ T cell activation, which lacks effective treatment and has a poor prognosis. Acacetin is a natural flavonoid product that has been reported to have anti-inflammatory effects. However, acacetin has not been investigated in myocarditis. METHODS: Oral acacetin treatment was administered in an experimental autoimmune myocarditis model established with myosin heavy chain-alpha peptide. Echocardiography, pathological staining, and RT-qPCR were used to detect cardiac function, myocardial injury, and inflammation levels. Flow cytometry was utilized to detect the effect of acacetin on CD4+ T cell function. RNA-seq, molecular docking, and microscale thermophoresis (MST) were employed to investigate potential mechanisms. Seahorse analysis, mitoSOX, JC-1, and mitotracker were utilized to detect the effect of acacetin on mitochondrial function. RESULTS: Acacetin attenuated cardiac injury and fibrosis as well as heart dysfunction, and reduced cardiac inflammatory cytokines and ratio of effector CD4+ T and Th17 cells. Acacetin inhibited CD4+ T cell activation, proliferation, and Th17 cell differentiation. Mechanistically, the effects of acacetin were related to reducing mitochondrial complex II activity thereby inhibiting mitochondrial respiration and mitochondrial reactive oxygen species in CD4+ T cells. CONCLUSION: Acacetin may be a valuable therapeutic drug in treating CD4+ T cell-mediated myocarditis.

Metabolism-Based Nontarget-Site Mechanism Is the Main Cause of a Four-Way Resistance in Shortawn Foxtail (Alopecurus aequalis Sobol.).

Alopecurus aequalis Sobol. is a predominant grass weed in Chinese winter wheat fields, posing a substantial threat to crop production owing to its escalating herbicide resistance. This study documented the initial instance of an A. aequalis population (AHFT-3) manifesting resistance to multiple herbicides targeting four distinct sites: acetyl-CoA carboxylase (ACCase), acetolactate synthase, photosystem II, and 1-deoxy-d-xylulose-5-phosphate synthase. AHFT-3 carried an Asp-to-Gly mutation at codon 2078 of ACCase, with no mutations in the remaining three herbicide target genes, and exhibited no overexpression of any target gene. Compared with the susceptible population AHFY-3, AHFT-3 metabolized mesosulfuron-methyl, isoproturon, and bixlozone faster. The inhibition and comparison of herbicide-detoxifying enzyme activities indicated the participation of cytochrome P450s in the resistance to all four herbicides, with glutathione S-transferases specifically linked to mesosulfuron-methyl. Three CYP72As and a Tau class glutathione S-transferase, markedly upregulated in resistant plants, potentially played pivotal roles in the multiple-herbicide-resistance phenotype.

Effect of blood viscosity on the hemodynamics of arteriovenous fistulae based on numerical investigation.

Arteriovenous fistula (AVF) is the most commonly used vascular access for hemodialysis in patients with end-stage renal disease. Vascular diseases such as atherosclerosis and thrombosis, triggered by altered hemodynamic conditions, are the main causes of access failure. Changes in blood viscosity accelerate access dysfunction by affecting local velocities and wall shear stress (WSS) distribution in the circulation. Numerical simulation was employed to analyze and compare the hemodynamic behavior of AVF under different blood viscosities (0.001-0.012 Pa∙s). An idealized three-dimensional model with end-to-side anastomosis was established. Transient simulations were conducted using pulsatile inlet velocity and outflow as boundary conditions. The simulation results reveal the blood flow state of AVF under different viscosity physiological conditions and derive the rule of change. When blood viscosity increases, the local velocity in the disturbed region slows down and the stagnation time becomes longer, resulting in increased deposition of substances. As blood viscosity increases, the level of shear stress on the entire wall of the fistula increases accordingly. WSS values at high viscosities above 0.007 Pa∙s showed significantly larger low-shear regions near the anastomosis and increased chances of inducing atheromatous plaques. This research has revealed the correlation between blood dynamic viscosity and the hemodynamic behavior of AVF. Elevated whole blood viscosity increases the incidence of access obstruction and vascular disease leading to fistula failure. The study provides a basis for optimizing the distribution of hemodynamic parameters in the fistula for hemodialysis patients.

Occurrence of ochratoxin A in Sichuan bacon from different geographical regions and characterization and biocontrol of ochratoxigenic Aspergillus westerdijkiae strain 21G2-1A.

Sichuan bacon represents the most prevalent dry-cured meat product across Southwest China, but it is vulnerable to fungal spoilage. In the present study, a total of 47 Sichuan bacons were obtained from different regions of the Sichuan Province and analyzed for the presence of ochratoxin A (OTA), yielding a positive rate of 23.4 % (11/47). All the observed OTA concentrations exceeded the maximum admissible dose in meat products (1 µg/kg) established by some EU countries, with the highest OTA concentration being 250.75 µg/kg, which raises a food safety concern and reveals the need for a standardized scientific processing protocol. Then, an OTA-producing fungus named 21G2-1A was isolated from positive samples and found to be Aspergillus westerdijkiae. Further characterization suggested a positive correlation between fungal growth and OTA production. The optimal temperature for the former was 25 °C, while it was 20 °C for the latter. Although the A. westerdijkiae strain 21G2-1A demonstrated greater mycelium growth in the presence of NaCl, OTA production was significantly dismissed when the salinity was greater than 5 %. Four lactic acid bacteria (LAB) were screened out as antagonists against the ochratoxigenic fungus. In vitro evaluation of the antagonists revealed that live cells inhibited fungal growth, and adsorption also contributed to OTA removal at different levels. This study sheds some light on OTA control in Sichuan bacon through a biological approach.

Revealing the Indispensable Role of In Situ Electrochemically Reconstructed Mn(II)/Mn(III) in Improving the Performance of Lithium-Carbon Dioxide Batteries.

Li-CO2 batteries are regarded as promising high-energy-density energy conversion and storage devices, but their practicability is severely hindered by the sluggish CO2 reduction/evolution reaction (CORR/COER) kinetics. Due to the various crystal structures and unique electronic configuration, Mn-based cathode catalysts have shown considerable competition to facilitate CORR/COER. However, the specific active sites and regulation principle of Mn-based catalysts remain ambiguous and limited. Herein, this work designs novel Mn dual-active sites (MOC) supported on N-doped carbon nanofibers and conduct a comprehensive investigation into the underlying relationship between different Mn active sites and their electrochemical performance in Li-CO2 batteries. Impressively, this work finds that owing to the in situ generation and stable existence of Mn(III), MOC undergoes obvious electrochemical reconstruction during battery cycling. Moreover, a series of characterizations and theoretical calculations demonstrate that the different electronic configurations and coordination environments of Mn(II) and Mn(III) are conducive to promoting CORR and COER, respectively. Benefiting from such a modulating behavior, the Li-CO2 batteries deliver a high full discharge capacity of 10.31 mAh cm-2, and ultra-long cycle life (327 cycles/1308 h). This fundamental understanding of MOC reconstruction and the electrocatalytic mechanisms provides a new perspective for designing high-performance multivalent Mn-integrated hybrid catalysts for Li-CO2 batteries.

The circMYBL2-encoded p185 protein suppresses colorectal cancer progression by inhibiting serine biosynthesis.

Circular RNAs (circRNAs) are a class of covalently closed single-stranded loop RNAs that have been implicated to play a functional role in almost all types of cancers. Previous studies have revealed that circMYBL2 acts as a tumor-promoting circRNA. Here, we found that circMYBL2 in colorectal cancer (CRC) encodes a 185-amino acid protein, p185. Functionally, circMYBL2-encoded p185 suppressed the growth and aggressiveness of CRC cells in vitro and in vivo. Mechanistically, p185 counteracted UCHL3-mediated deubiquitination of phosphoglycerate dehydrogenase (PHGDH) by competitively binding to the C1 domain of UCHL3, resulting in PHGDH degradation and a subsequent reduction in serine and glycine biosynthesis. These data revealed that the circMYBL2-encoded p185 isoform serves as a tumor suppressor to inhibit the progression of CRC by reducing serine biosynthesis.

The Cys-2088-Arg mutation in the ACCase gene and enhanced metabolism confer cyhalofop-butyl resistance in Chinese sprangletop (Leptochloa chinensis).

Acetyl-CoA carboxylase (ACCase)-inhibiting herbicides are among the most commonly used herbicides to control grassy weeds, especially Leptochloa chinensis, in rice fields across China. Herein, we collected a suspected resistant (R) population of L. chinensis (HFLJ16) from Lujiang county in Anhui Province. Whole plant dose response tests showed that, compared with the susceptible (S) population, the R population showed high resistance to cyhalofop-butyl (22-fold) and displayed cross-resistance to metamifop (9.7-fold), fenoxaprop-P-ethyl (18.7-fold), quizalofop-P-ethyl (7.6-fold), clodinafop-propargyl (12-fold) and clethodim (8.4-fold). We detected an amino acid substitution (Cys-2088-Arg) in the ACCase of resistant L. chinensis. However, ACCase gene expression levels were not significantly different (P > 0.05) between R plants and S plants, without or with cyhalofop-butyl treatment. Furthermore, pretreatment with piperonyl butoxide (PBO, a cytochrome P450 monooxygenase (CYP450) inhibitor) or 4-chloro-7-nitrobenzoxadiazole (NBD-Cl, a glutathione-S-transferase (GST) inhibitor), inhibited the resistance of the R population to cyhalofop-butyl significantly (by approximately 60% and 26%, respectively). Liquid chromatography tandem mass spectrometry analysis showed that R plants metabolized cyhalofop-butyl and cyhalofop acid (its metabolite) significantly faster than S plants. Three CYP450 genes, one GST gene, and two ABC transporter genes were induced by cyhalofop-butyl and were overexpressed in the R population. Overall, GST-associated detoxification, CYP450 enhancement, and target-site gene mutation are responsible for the resistance of L. chinensis to cyhalofop-butyl.

Safety and Efficacy of the Erbium Laser in Debonding Dental Accessories: A Narrative Review.

Objective: This article aims to review the safety and efficacy of the Er:YAG laser in debonding dental accessories. Methods: This review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement. Articles published between 2010 and 2022 on the removal of dental accessories using erbium laser were searched. The selected articles were then classified according to the accessories used: adhesives, brackets, restorations, or implant crowns. Enamel surface roughness, shear bond strength, adhesive remnant index, duration time (t), pulp chamber temperature (T), morphology (M), and other variables were then noted. Results: The dental accessories and adhesives used were described along with the laser parameters used, such as frequency, pulse width, irradiation time, scanning mode, water-air cooling, and other variables. Conclusions: Laser removal using Er:YAG laser of dental accessories such as brackets, crowns, and veneers is fundamentally safe, time-saving, and does not cause damage to the enamel nor the underlying dentin. However, there was no distinct advantage with laser removal seen, such as those residual adhesives of brackets on the tooth surface and temporary adhesives of restorations.

[Left mandibular osteonecrosis following herpes zoster of the third branch of left trigeminal nerve: A case report].

Herpes zoster of trigeminal nerve was a common skin disease caused by varicella-zoster virus infection. Simple involvement of the third branch of trigeminal nerve was rare, and so were oral complications such as pulpitis, periodontitis, spontaneous tooth loss, bone necrosis, etc. This article presented a case of herpes zoster on the third branch of the left trigeminal nerve complicated with left mandibular osteonecrosis. We reported the case of a 64-year-old man with sudden pain in the left half of the tongue 1 month ago, and then herpes on the left facial skin appeared following with acute pain.The local hospital diagnosed it as herpes zoster and treated it with external medication. A few days later, he developed gum pain in the left mandibular posterior tooth area. He was admitted to Peking University School and Hospital of Stomatology one week ago with loose and dislodged left posterior tooth accompanied by left mandibular bone surface exposure. Clinical examination showed bilateral symmetry and no obvious restriction of mouth opening. Visible herpes zoster pigmentation and scarring on the left side of the face appeared. The left mandibular posterior tooth was missing, the exposed bone surface was about 1.5 cm×0.8 cm, and the surrounding gingiva was red and swollen, painful under pressure, with no discharge of pus. The remaining teeth in the mouth were all Ⅲ degree loosened. Imageological examination showed irregular low-density destruction of the left mandible bone, unclear boundary, and severe resorption of alveolar bone. The patient was diagnosed as left mandibular osteonecrosis. Under general anesthesia, left mandibular lesion exploration and curettage + left mandibular partial resection + adjacent flap transfer repair were performed. The patient was re-exmained 6 months after surgery, there was no redness, swelling or other abnormality in the gums and the herpes pigmentation on the left face was significantly reduced. Unfortunately, the patient had complications of postherpetic neuralgia. This case indicate that clinicians should improve their awareness of jaw necrosis, a serious oral complication of trigeminal zoster, and provide early treatment. After the inflammation was initially controlled, surgical treatment could be considered to remove the necrotic bone, curettage the inflammatory granulation tissue, and extraction of the focal teeth to avoid further deterioration of the disease.

Trajectory of COVID-19 response and management strategy in China: scientific rationale driven strategy adjustments.

The pneumonia caused by novel coronavirus SARS-CoV-2 infection in early December 2019, which was later named coronavirus disease 2019 (COVID-19) by the World Health Organization (WHO), rapidly spread across the world. China has made extraordinary efforts to this unprecedented pandemic, put its response and control at a very high level of infectious disease management (Category B but with measures for Category A), given top priority to the people and their lives, and balanced the pandemic control and socio-economic development. After more than three years' fighting against this disease, China downgraded the management of COVID-19 to Category B infectious disease on January 8, 2023 and the WHO declared the end of public health emergency on May 5, 2023. However, the ending of pandemic does not mean that the disease is no longer a health threat. Experiences against COVID-19 from China and the whole world should be learned to prepare well for the future public health emergencies. This article gives a systematic review of the trajectory of COVID-19 development in China, summarizes the critical policy arrangements and provides evidence for the adjustment during policy making process, so as to share experiences with international community and contribute to the global health for all humanity.