In vivo CRISPR screens identify the E3 ligase Cop1 as a modulator of macrophage infiltration and cancer immunotherapy target.

Despite remarkable clinical efficacy of immune checkpoint blockade (ICB) in cancer treatment, ICB benefits for triple-negative breast cancer (TNBC) remain limited. Through pooled in vivo CRISPR knockout (KO) screens in syngeneic TNBC mouse models, we found that deletion of the E3 ubiquitin ligase Cop1 in cancer cells decreases secretion of macrophage-associated chemokines, reduces tumor macrophage infiltration, enhances anti-tumor immunity, and strengthens ICB response. Transcriptomics, epigenomics, and proteomics analyses revealed that Cop1 functions through proteasomal degradation of the C/ebpδ protein. The Cop1 substrate Trib2 functions as a scaffold linking Cop1 and C/ebpδ, which leads to polyubiquitination of C/ebpδ. In addition, deletion of the E3 ubiquitin ligase Cop1 in cancer cells stabilizes C/ebpδ to suppress expression of macrophage chemoattractant genes. Our integrated approach implicates Cop1 as a target for improving cancer immunotherapy efficacy in TNBC by regulating chemokine secretion and macrophage infiltration in the tumor microenvironment.

Systematic characterization of mutations altering protein degradation in human cancers.

The ubiquitin-proteasome system (UPS) is the primary route for selective protein degradation in human cells. The UPS is an attractive target for novel cancer therapies, but the precise UPS genes and substrates important for cancer growth are incompletely understood. Leveraging multi-omics data across more than 9,000 human tumors and 33 cancer types, we found that over 19% of all cancer driver genes affect UPS function. We implicate transcription factors as important substrates and show that c-Myc stability is modulated by CUL3. Moreover, we developed a deep learning model (deepDegron) to identify mutations that result in degron loss and experimentally validated the prediction that gain-of-function truncating mutations in GATA3 and PPM1D result in increased protein stability. Last, we identified UPS driver genes associated with prognosis and the tumor microenvironment. This study demonstrates the important role of UPS dysregulation in human cancer and underscores the potential therapeutic utility of targeting the UPS.

Background-suppressed tumor-targeted photoacoustic imaging using bacterial carriers.

Photoacoustic (PA) imaging offers promise for biomedical applications due to its ability to image deep within biological tissues while providing detailed molecular information; however, its detection sensitivity is limited by high background signals that arise from endogenous chromophores. Genetic reporter proteins with photoswitchable properties enable the removal of background signals through the subtraction of PA images for each light-absorbing form. Unfortunately, the application of photoswitchable chromoproteins for tumor-targeted imaging has been hampered by the lack of an effective targeted delivery scheme; that is, photoswitchable probes must be delivered in vivo with high targeting efficiency and specificity. To overcome this limitation, we have developed a tumor-targeting delivery system in which tumor-homing bacteria (Escherichia coli) are exploited as carriers to affect the point-specific delivery of genetically encoded photochromic probes to the tumor area. To improve the efficiency of the desired background suppression, we engineered a phytochrome-based reporter protein (mDrBphP-PCMm/F469W) that displays higher photoswitching contrast than those in the current state of the art. Photoacoustic computed tomography was applied to achieve good depth and resolution in the context of in vivo (mice) imaging. The present system effectively integrates a genetically encoded phytochrome-based reporter protein, PA imaging, and synthetic biology (GPS), to achieve essentially background-suppressed tumor-targeted PA monitoring in deep-seated tissues. The ability to image tumors at substantial depths may enable target-specific cancer diagnoses to be made with greater sensitivity, fidelity, and specificity.

Dissecting the temporal genetic networks programming soybean embryo development from embryonic morphogenesis to post-germination.

KEY MESSAGE: Desiccation-stage transcription factors perform similar functions, with early ones focused on desiccation tolerance and later ones on development. Gene networks governing late embryo development diverge between soybean and Arabidopsis. To understand gene activities programming seed embryo development, we profiled the soybean embryo transcriptome across embryonic morphogenesis through post-germination. Transcriptomic landscapes across embryo development feature highly prevalent transcripts, categorized into early and late groups, with shared and distinct functions. During the mid-storage reserve accumulation stage, the upregulated genes are enriched with regulatory tasks at both the transcriptional and chromatin levels, including DNA methylation and chromatin remodeling. The epigenetic-related functions also dominate in the upregulated genes during germination, involving core histone variants and histone chaperones. Gene network analysis reveals both stage-specific modules and modules active across multiple stages. The desiccation-associated gene module integrates diverse transcription factors (TFs) that are sequentially active during different desiccation stages, transitioning from abiotic stress functions early on to developmental functions later. Two TFs, active during the early and mid-desiccation stages were functionally assessed in Arabidopsis overexpression lines to uncover their potential roles in desiccation processes. Interestingly, nearly half of the Arabidopsis orthologs of soybean TFs active in the desiccation-associated module are inactive during Arabidopsis desiccation. Our results reveal that chromatin and transcriptional regulation coordinate during mid-storage reserve accumulation, while distinct epigenetic mechanisms drive germination. Additionally, gene modules either perform stage-specific functions or are required across multiple stages, and gene networks during late embryogenesis diverge between soybean and Arabidopsis. Our studies provide new information on the biological processes and gene networks underlying development from embryonic morphogenesis to post-germination.

Radiographic features and subtypes of congenital thumb duplication type C3 according to Wu et al. and their potential implications for surgical management: new classification and preliminary results.

BACKGROUND: Wu et al. introduced a modified radiographic system that allows classification of all forms of CTD with excellent interobserver and intraobserver reliability. No study to date has evaluated the radiographic characteristics of Wu et al. type C3 CTD with osseous attachment at the level of the metacarpal. OBJECTIVE: This study aimed to evaluate the radiographic features of type C3 CTD according to the system of Wu et al., to describe the different anatomical subtypes of the duplication, and to propose a categorization approach to distinguish diverse surgical strategies based on the radiographic anatomy of this specific subtype of duplication. METHODS: We performed a retrospective analysis of 215 patients (221 thumbs) diagnosed with Wu et al. type C3 CTD at our Institution between 2015 and 2021. We evaluated all CTDs by examining the alignment of the interphalangeal (IP) and metacarpophalangeal (MP) joints and by assessing the presence of abnormal hypertrophic epiphysis of the primary thumb on posteroanterior (PA) radiographs. The proposed classification system has four types: Type I with good alignment of both MP and IP joints, Type II with ulnar deviation of the MP joint, Type III with radial deviation in the MP joint and Type IV with abnormal hypertrophic epiphysis of the distal phalanx of the main thumb with ulnar deviation of the IP joint with or without ulnar deviation of the MP joint. RESULTS: There were 140 male and 75 female patients with CTD (221 thumbs). There were 65 left, 144 right and 6 bilateral forms. The right-to-left, male-to-female and unilateral-to-bilateral ratios were 2.2:1, 1.9:1 and 35.8:1 respectively. The mean age at surgery was 22.3 ± 11.8 months (range, 8-80). The proposed classification system allowed the classification of all CTDs (n = 221). Specifically, 53 fingers were classified as Type I (24%), 136 as Type II (61.5%), 21 as Type III (9.5%), and 11 as Type IV (5%). CONCLUSION: The proposed system is based on radiographic pathoanatomy and complements that of Wu et al. by identifying four distinct subtypes of deformity. It has the potential to improve inter-professional communication and guide surgery in patients with Wu et al. type C3 CTD. However, our results are preliminary and further research is needed to validate them. LEVEL OF EVIDENCE: III.

High-speed chaos-based secure optical communications over 130-km multi-core fiber.

Chaotic optical communication is of great significance for secure data transmission. Despite rapid development over the decades, high-speed (>100 Gbps) and long-distance (>100 km) chaotic optical communication in a single fiber is still full of challenges. Here, we propose and experimentally demonstrate high-speed and long-distance chaos-based secure optical communications using mutual injection of semiconductor lasers and space-division multiplexing (SDM) techniques. The encrypted signals are transmitted through all seven core channels of the multi-core fiber (MCF), which effectively expands the aggregate transmission capacity of a single fiber. A pair of source and synchronization devices based on mutual injection of semiconductor lasers are employed to effectively encrypt and decrypt signals. Chaos-based secure optical communications with 70-Gbps on-off keying (OOK) and 140-Gbps quadrature phase-shift keying (QPSK) signals over a 130-km MCF are successfully demonstrated in the experiment with favorable performance. The demonstration may pave the way for future ultrahigh capacity and ultra-long distance chaotic optical communications by fully exploiting multi-dimensional resources of light waves, including the spatial dimension.

CircRNA CircABCB1 Diminishes the Sensitivity of Breast Cancer Cells to Docetaxel by Sponging MiR-153-3p.

Resistance to docetaxel is a major problem to the success of docetaxel-based therapies for breast cancer. The present study was to identify the role of circABCB1 in altering the docetaxel resistance properties. Reverse transcription-quantitative PCR (qRT-PCR) was performed to quantify circABCB1 and miR-153-3p. The effects of circABCB1 on the viability, apoptosis and migration/invasion of docetaxel-resistant and -sensitive cells were investigated by cell function experiments, including Cell Counting Kit-8 and Transwell assays. Correlation between circABCB1 and the docetaxel-treated outcome was analyzed by multivariate Cox regression analysis, in addition to Kaplan-Meier analysis of time to treatment failure (TTF). The targeting relationship between circABCB1 and miR-153-3p was predicted and verified by dual-luciferase reporter assay and RNA immunoprecipitation. CircABCB1 was highly expressed in cancerous tissues, as well as the docetaxel-sensitive group and cells. The overexpression of circABCB1 contributed to cell viability, docetaxel-resistance and migration/invasion, but inhibited apoptosis. CircABCB1 can sponge miR-153-3p. CircABCB1 contributed to the docetaxel resistance of breast cancer, maybe via the miR-153-3p.

Mechanical Polarization Switching in Hf0.5Zr0.5O2 Thin Film.

HfO2-based films with high compatibility with Si and complementary metal-oxide semiconductors (CMOS) have been widely explored in recent years. In addition to ferroelectricity and antiferroelectricity, flexoelectricity, the coupling between polarization and a strain gradient, is rarely reported in HfO2-based films. Here, we demonstrate that the mechanically written out-of-plane domains are obtained in 10 nm Hf0.5Zr0.5O2 (HZO) ferroelectric film at room temperature by generating the stress gradient via the tip of an atomic force microscope. The results of scanning Kelvin force microscopy (SKPM) exclude the possibility of flexoelectric-like mechanisms and prove that charge injection could be avoided by mechanical writing and thus reveal the true polarization state, promoting wider flexoelectric applications and ultrahigh-density storage of HZO thin films.

[Role of nanomaterials in the diagnosis of prostate cancer: An update].

Prostate cancer (PCa) is one of the most common malignant tumors of the genitourinary system in middle-aged and elderly men. The incidence of PCa has been increasing year by year in China in recent years, posing a major threat to the physical and mental health of Chinese men. With the rapid development of nanotechnology, the research of nanomaterials in biomedicine is increasing, which effectively promotes the application of nanomaterials in the early diagnosis of a variety of tumors, including PCa. This article reviews the latest research progress of nanomaterials in the diagnosis of PCa.

[Non-rigid registration for medical images based on deformable convolution and multi-scale feature focusing modules].

Non-rigid registration plays an important role in medical image analysis. U-Net has been proven to be a hot research topic in medical image analysis and is widely used in medical image registration. However, existing registration models based on U-Net and its variants lack sufficient learning ability when dealing with complex deformations, and do not fully utilize multi-scale contextual information, resulting insufficient registration accuracy. To address this issue, a non-rigid registration algorithm for X-ray images based on deformable convolution and multi-scale feature focusing module was proposed. First, it used residual deformable convolution to replace the standard convolution of the original U-Net to enhance the expression ability of registration network for image geometric deformations. Then, stride convolution was used to replace the pooling operation of the downsampling operation to alleviate feature loss caused by continuous pooling. In addition, a multi-scale feature focusing module was introduced to the bridging layer in the encoding and decoding structure to improve the network model's ability of integrating global contextual information. Theoretical analysis and experimental results both showed that the proposed registration algorithm could focus on multi-scale contextual information, handle medical images with complex deformations, and improve the registration accuracy. It is suitable for non-rigid registration of chest X-ray images.

Peroxisome proliferator activated receptor-γ agonist pioglitazone improves vascular and metabolic dysfunction in systemic lupus erythematosus.

OBJECTIVES: Premature cardiovascular events in systemic lupus erythematosus (SLE) contribute to morbidity and mortality, with no effective preventive strategies described to date. Immune dysregulation and metabolic disturbances appear to play prominent roles in the induction of vascular disease in SLE. The peroxisome proliferator activated receptor-gamma agonist pioglitazone (PGZ suppresses vascular damage and immune dysregulation in murine lupus and improves endothelial dysfunction in other inflammatory diseases. We hypothesised that PGZ could improve vascular dysfunction and cardiometabolic parameters in SLE. METHODS: Eighty SLE subjects with mild to severe disease activity were randomised to a sequence of PGZ followed by placebo for 3 months, or vice versa, in a double-blind, cross-over design with a 2-month wash-out period. Primary endpoints were parameters of endothelial function and arterial inflammation, measured by multimodal assessments. Additional outcome measures of disease activity, neutrophil dysregulation, metabolic disturbances and gene expression studies were performed. RESULTS: Seventy-two subjects completed the study. PGZ was associated with a significant reduction in Cardio-Ankle Vascular Index (a measure of arterial stiffness) compared with placebo. Various metabolic parameters improved with PGZ, including insulin resistance and lipoprotein profiles. Circulating neutrophil extracellular trap levels also significantly decreased with PGZ compared with placebo. Most adverse events experienced while on PGZ were mild and resolved with reduction in PGZ dose. CONCLUSION: PGZ was well tolerated and induced significant improvement in vascular stiffness and cardiometabolic parameters in SLE. The results suggest that PGZ should be further explored as a modulator of cardiovascular disease risk in SLE. TRIAL REGISTRATION NUMBER: NCT02338999.

Real-world study on HBsAg loss of combination therapy in HBeAg-negative chronic hepatitis B patients.

Combination therapy with pegylated interferon (PEG-IFN) and nucleos(t)ide analogues (NAs) can enhance hepatitis B surface antigen (HBsAg) clearance. However, the specific treatment strategy and the patients who would benefit the most are unclear. Therefore, we assessed the HBsAg loss rate of add-on PEG-IFN and explored the factors associated with HBsAg loss in chronic hepatitis B (CHB) patients. This was a real-world cohort study of adults with CHB. Hepatitis B e antigen (HBeAg)-negative NAs-treated patients with baseline HBsAg ≤1500 IU/ml and HBV DNA < the lower limit of detection, or 100 IU/ml, received 48 weeks of add-on PEG-IFN. The primary outcome of the study was the rate of HBsAg loss at 48 weeks of combination treatment. Using multivariable logistic regression analysis, we determined factors associated with HBsAg loss. HBsAg loss in 2579 patients (mean age: 41.2 years; 80.9% male) was 36.7% (947 patients) at 48 weeks. HBsAg loss was highest in patients from south-central and southwestern China (40.0%). Factors independently associated with HBsAg loss included: increasing age (odds ratio = 0.961); being male (0.543); baseline HBsAg level (0.216); HBsAg decrease at 12 weeks (between 0.5 and 1.0 log10 IU/ml [2.405] and >1.0 log10 IU/ml [7.370]); alanine aminotransferase (ALT) increase at 12 weeks (1.365); haemoglobin (HGB) decrease at 12 weeks (1.558). There was no difference in the primary outcomes associated with the combination regimen. In conclusion, HBsAg loss by combination therapy was higher in patients from southern China than those from the north. An increased chance of HBsAg loss was associated with baseline characteristics and dynamic changes in clinical indicators.

Hepatocyte steatosis inhibits hepatitis B virus secretion via induction of endoplasmic reticulum stress.

The effects of hepatocyte steatosis on hepatitis B virus (HBV) DNA replication and HBV-related antigen secretion are incompletely understood. The aims of this study are to explore the effects and mechanism of hepatocyte steatosis on HBV replication and secretion. Stearic acid (SA) and oleic acid (OA) were used to induce HepG2.2.15 cell steatosis in this study. The expressions of glucose-regulated protein 78 (GRP78), phosphorylation of protein kinase R-like endoplasmic reticulum (ER) kinase (p-PERK), and eukaryotic translation initiation factor 2α (p-eIF2α) were detected by Western blotting (WB). HBV DNA, HBsAg, and HBeAg in the supernatant were determined by real-time fluorescent polymerase chain reaction (PCR) and enzyme-linked immunosorbent assay. Intracellular HBV DNA, HBsAg level, and HBV RNA were measured by real-time fluorescent PCR, WB, and real-time quantitative reverse transcriptase-PCR, respectively. The results showed that SA and OA significantly increased intracellular lipid droplets and triglyceride levels. SA and OA significantly induced GRP78, p-PERK, and p-eIF2α expressions from 24 to 72 h. 4-phenylbutyric acid (PBA) alleviated ER stress induced by SA. SA promoted intracellular HBsAg and HBV DNA accumulation; however, it inhibited the transcript of HBV 3.5 kb mRNA and S mRNA. The secretion of HBsAg and HBV DNA inhibited by SA or OA could be partially restored by pretreatment with PBA but not by inhibiting GRP78 expression with siRNA. Hepatocyte steatosis inhibits HBsAg and HBV DNA secretion via induction of ER stress in hepatocytes, but not via induction of GRP78.

Use of gonadotropin-releasing hormone agonists for ovarian preservation in patients receiving cyclophosphamide for systemic lupus erythematosus: A meta-analysis.

BACKGROUND: Cyclophosphamide (CYC) has known cytotoxic effects on ovarian reserve and has been linked to premature ovarian failure (POF) in systemic lupus erythematosus (SLE). The concurrent use of gonadotropin-releasing hormone agonists (GnRHas) is postulated to preserve ovarian function by reducing the number of follicles exposed to CYC, but there is paucity of data to establish its efficacy. We conducted a meta-analysis to summarize the effect of concurrent GnRHa use in persevering ovarian function and pregnancy. METHODS: English language databases of PubMed, Embase, and Cochrane were searched to include studies published between 2000 and 2021. Studies in females with rheumatic diseases receiving concurrent GnRHa and CYC therapy to evaluate ovarian preservation as defined by amenorrhea, follicle stimulating hormone (FSH), anti-mullerian hormone (AMH), or estradiol levels or successful pregnancy were included. We used a fixed effect, exact, Mantel-Haenszel approach to estimate the overall odds ratio (OR) and associated 95% confidence intervals (95% CIs). RESULTS: Seven studies with 218 female patients were included. The ovarian function was preserved in 125/132 (94.6%) of women who received GnRHa concurrently with CYC compared to 50/86 (58%) of women who did not receive GnRHa (OR = 10.3, CI = 4.83-36.29). The OR for pregnancy with GnRHa use = 2.94 (CI = 1.04-9.89). CONCLUSION: Our results based on limited published studies suggest that concurrent GnRHa use preserves ovarian function and increase odds of pregnancy. It can be considered for premenopausal SLE females receiving CYC. Long-term follow-up studies are needed to establish the efficacy and safety of GnRHa use for ovarian preservation.

Mesenchymal Stem Cell-Derived Extracellular Vesicles Therapy for Pulmonary Hypertension: A Comprehensive Review of Preclinical Studies.

Pulmonary hypertension (PH) is a type of clinical pathophysiological syndrome characterized by a progressive increase in pulmonary vascular resistance and subsequent progressive failure of the right heart function, and is a common complication of many diseases. Mesenchymal stem cells (MSCs) autonomously home to sites damaged by disease, repair damaged tissues, and participate in the regulation of systemic inflammation and immune responses, which have good clinical application prospects. Extracellular vesicles (EVs), such as exosomes and microvesicles, participate in various biological activities by regulating intercellular communication. Exosomes secreted into the extracellular environment also affect the host immune system. MSC-derived extracellular vesicles (MSC-EVs), as a mediator in the paracrine processes of MSCs, carry biologically active substances such as proteins, lipids, mRNA, and micro-RNA. MSC-EVs therapies, safer than cell-based treatments, have been shown to be effective in modulating macrophages to support anti-inflammatory phenotypes, which are strongly related to histological and functional benefits in preclinical models of pulmonary hypertension. The main effects of active substances and their potential medical value have attracted wide attention from researchers. This article reviews the role and relevant mechanisms of MSC-EVs in the treatment of pulmonary hypertension in recent studies and provides a basis for their future clinical applications.

Meconium-Stained Amniotic Fluid: Impact on Prognosis of Neonatal Bacterial Meningitis.

OBJECTIVES: Clinical data with respect to the impact of meconium on the prognosis of neonatal bacterial meningitis are scarce. Therefore, in this study, we aimed to determine whether meconium-stained amniotic fluid (MSAF) represents a risk factor for poor prognosis of neonatal bacterial meningitis in a confirmed case population. METHODS: This was a retrospective cohort study of 256 neonates diagnosed with bacterial meningitis hospitalized at one of three hospitals in Shantou, China, between October 2013 and September 2018. Clinical manifestation, laboratory test results and treatment were compared between the two groups, with outcomes dichotomized into 'good' or 'poor' prognosis. Multivariate analysis and follow-up logistic regression analysis were used to identify predictive factors of a poor outcome. RESULTS: Of the 256 neonates with BM, 95 (37.1%) had a good prognosis at discharge and 161 (62.9%) had a poor prognosis. In the poor prognosis group, 131/161 (79.4%) neonates had a permanent neurological sequelae and 19 (11.8%) had ≥2 sequelae. Of note, 11 neonates died. The rate of poor prognosis of BM was significantly higher among neonates with than without MSAF (26.1% vs. 12.6%, respectively; p < 0.05). A logistic multivariate analysis to evaluate the prognostic effect of MSAF to BM showed that neonatal with MSAF is more likely to have a worse prognosis of BM [unadjusted odds ratio (OR), 2.44, 95% confidence interval (CI), 1.24-5.10; adjusted OR, 2.31; 95% CI, 1.09-5.17]. CONCLUSION: MSAF is significantly associated with poor prognosis of neonatal bacterial meningitis. Therefore, in case of MSAF, more attention should be paid to neonatal bacterial meningitis.

The clinical value of dual-energy computed tomography and diffusion-weighted imaging in the context of liver cancer: A narrative review.

The dual-energy computed tomography (DECT) and diffusion-weighted magnetic resonance imaging (DWI-MRI) are used to diagnose liver cancer. The clinical value of these two examination methods needs to be further summarized. We collected and summarized relevant literature published from 2011 to 2021. The diagnostic performance of DECT was assessed between conventional computed tomography and DWI-MRI. DWI-MRI had a 69% sensitivity for detecting small hepatocellular carcinoma (HCC) lesions and a 60% diagnostic specificity for differentiating between types of HCC lesions. DECT had a sensitivity to small liver lesions (<1 cm) of 69%, and the diagnostic specificity for HCC and metastasis was about 60%. DWI was more sensitive (90.3% vs. 74.9%) and accurate (91.9% vs. 76.9%) in diagnosing HCC compared with conventional MRI sequencing. With the aid of contrast media, DWI-MRI had 90.0% specificity for detecting small HCCs (smaller than 1 cm). Furthermore, DWI-MRI not only provided physicians with valuable diagnostic information but also delivered histological grading information, with 78% accuracy for all benign lesions and 71% for solid lesions. DECT had relatively high sensitivity and required a lower contrast medium dose. With standardized quantitative parameters, it can be an extremely useful tool for HCC surveillance. DWI-MRI is the preferred imaging process as it produces high-contrast images for supporting an early diagnosis (high sensitivity and specificity) and provides histological information using non-ionizing radiation.

Simultaneous Real-Time Three-Dimensional Localization and FRET Measurement of Two Distinct Particles.

Many biological processes employ mechanisms involving the locations and interactions of multiple components. Given that most biological processes occur in three dimensions, the simultaneous measurement of three-dimensional locations and interactions is necessary. However, the simultaneous three-dimensional precise localization and measurement of interactions in real time remains challenging. Here, we report a new microscopy technique to localize two spectrally distinct particles in three dimensions with an accuracy (2.35σ) of tens of nanometers with an exposure time of 100 ms and to measure their real-time interactions using fluorescence resonance energy transfer (FRET) simultaneously. Using this microscope, we tracked two distinct vesicles containing t-SNAREs or v-SNARE in three dimensions and observed FRET simultaneously during single-vesicle fusion in real time, revealing the nanoscale motion and interactions of single vesicles in vesicle fusion. Thus, this study demonstrates that our microscope can provide detailed information about real-time three-dimensional nanoscale locations, motion, and interactions in biological processes.

Role of B Lymphocytes in the Pathogenesis of NAFLD: A 2022 Update.

Non-alcoholic fatty liver disease and its related complications are becoming one of the most important health problems globally. The liver functions as both a metabolic and an immune organ. The crosstalk between hepatocytes and intrahepatic immune cells plays a key role in coordinating a dual function of the liver in terms of the protection of the host from antigenic overload as a result of receiving nutrients and gut microbiota antigenic stimulation via facilitating immunologic tolerance. B cells are the most abundant lymphocytes in the liver. The crucial role of intrahepatic B cells in energy metabolism under different immune conditions is now emerging in the literature. The accumulating evidence has demonstrated that the antibodies and cytokines produced by B cells in the microenvironment play key and distinct roles in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Herein, we have aimed to consolidate and update the current knowledge about the pathophysiological roles of B cells as well as the underlying mechanisms in energy metabolism. Understanding how B cells can exacerbate and suppress liver damage by exploiting the antibodies and cytokines they produce will be of great importance for designing B-cell targeting therapies to treat various liver diseases.

Effects of Extraction Technique on the Content and Antioxidant Activity of Flavonoids from Gossypium Hirsutum linn. Flowers.

Cotton is one of the Uyghur medical materials in China and is rich in flavonoids. Flavonoids have important pharmacological effects. The yield of flavonoids in traditional extraction methods is low, which affects the development of flavonoids. Therefore, it is urgent to optimize the extraction techniques. The yield of flavonoids in cotton flowers was effectively improved by response surface methodology, and the highest yield of flavonoids reached 5.66%, and the optimal extraction process conditions were obtained. The DPPH free radical scavenging rate, hydroxyl free radical scavenging rate, superoxide anion free radical scavenging rate, and reducing ability were tested to reflect the antioxidant capacity of flavonoids. The flavonoids had an excellent antioxidant effect. Cell experiments suggested that the flavonoids had the effect of protecting glutamate-induced damage to HT-22 cells. The results of this study provide a theoretical basis for the extraction of cotton flowers flavonoids and the comprehensive evaluation of antioxidant products, as well as the extraction of other plant flavonoids.