CRISPR/Cas13a-based rapid detection method for porcine deltacoronavirus.

Background: Porcine deltacoronavirus (PDCoV) is a newly discovered porcine intestinal pathogenic coronavirus with a single-stranded positive-sense RNA genome and an envelope. PDCoV infects pigs of different ages and causes acute diarrhea and vomiting in newborn piglets. In severe cases, infection leads to dehydration, exhaustion, and death in sick piglets, entailing great economic losses on pig farms. The clinical symptoms of PDCoV infection are very similar to those of other porcine enteroviruses. Although it is difficult to distinguish these viral infections without testing, monitoring PDCoV is very important because it can spread in populations. The most commonly used methods for the detection of PDCoV is qPCR, which is time-consuming and require skilled personnel and equipment. Many farms cannot meet the conditions required for detection. Therefore, it is necessary to establish a faster and more convenient method for detecting PDCoV. Aims: To establish a rapid and convenient detection method for PDCoV by combining RPA (Recombinase Polymerase Isothermal Amplification) with CRISPR/Cas13a. Methods: Specific RPA primers and crRNA for PDCoV were designed, and the nucleic acids in the samples were amplified with RPA. Fluorescent CRISPR/Cas13a detection was performed. We evaluated the sensitivity and specificity of the RPA-CRISPR/Cas13a assay using qPCR as the control method. Results: CRISPR/Cas13a-assisted detection was completed within 90 min. The minimum detection limit of PDCoV was 5.7 × 101 copies/µL. A specificity analysis showed that the assay did not cross-react with three other porcine enteroviruses. Conclusion: The RPA-CRISPR/Cas13a method has the advantages of high sensitivity, strong specificity, fast response, and readily accessible results, and can be used for the detection of PDCoV.

DeepBAM: a high-accuracy single-molecule CpG methylation detection tool for Oxford nanopore sequencing.

Recent nanopore sequencing system (R10.4) has enhanced base calling accuracy and is being increasingly utilized for detecting CpG methylation state. However, the robustness and universality of the methylation calling model in officially supplied Dorado remains poorly tested. In this study, we obtained heterogeneous datasets from human and plant sources to carry out comprehensive evaluations, which showed that Dorado performed significantly different across datasets. We therefore developed deep neural networks and implemented several optimizations in training a new model called DeepBAM. DeepBAM achieved superior and more stable performances compared with Dorado, including higher area under the ROC curves (98.47% on average and up to 7.36% improvement) and F1 scores (94.97% on average and up to 16.24% improvement) across the datasets. DeepBAM-based whole genome methylation frequencies have achieved >0.95 correlations with BS-seq on four of five datasets, outperforming Dorado in all instances. It enables unraveling allele-specific methylation patterns, including regions of transposable elements. The enhanced performance of DeepBAM paves the way for broader applications of nanopore sequencing in CpG methylation studies.

RPA-CRISPR-Cas13a-assisted detection method of transmissible gastroenteritis virus.

Background and aim: Transmissible gastroenteritis virus (TGEV) is a highly contagious gastrointestinal virus that causes diarrhea, vomiting, anorexia, dehydration, and weight loss in piglets. In clinical practice, it often occurs in mixed infections with other pathogens, and is therefore difficult to diagnose and prevent. It mainly harms piglets of about 2 weeks old, causing huge losses on farms. The clinical confirmation of TGEV usually requires a laboratory diagnosis, but traditional PCR and immunofluorescence assays have some limitations. Moreover, most farms in China are ill-equipped to accurately diagnose the disease. Therefore, a new detection method with high sensitivity and specificity and less dependence on instrumentation is required. Methods: We used recombinase polymerase amplification (RPA), combined with the nuclease characteristics of the activated Cas13a protein to establish a visual CRISPR-Cas13a-assisted detection method for TGEV by adding a reporter RNA with fluorescent and quenching moieties to the system. Result: We selected the optimal RPA primer and best CRISPR RNA (crRNA). The reaction system was optimized and its repeatability, specificity, and sensitivity verified. The TGEV detection system did not cross-react with other common diarrhea viruses, and its detection limit was 101 copies, which is similar with the sensitivity of qPCR. We successfully established an RPA-CRISPR-Cas13a-assisted detection method, and used this detection system to analyze 123 pig blood samples. qPCR was used as the gold standard method. The sensitivity, specificity, positive coincidence rate, and negative coincidence rate of the new method were 100, 98.93, 96.66, and 100%, respectively.

Decoding connections in the European population: serum uric acid, sex hormone-binding globulin, total testosterone, estradiol, and female infertility - advanced bidirectional and mediative Mendelian randomization.

Background: Despite observational links between serum uric acid (SUA), sex hormone-related phenotypes, and female infertility, the causality behind these associations remains uncertain. Objective: This study utilizes Bidirectional Two-Sample and Mediation Mendelian Randomization to explore the causal relationships and mediation effects of sex hormone-binding globulin (SHBG), total testosterone (TT), and estradiol on these associations. Methods: We analyzed single-nucleotide polymorphisms (SNPs) associated with SUA and sex hormone levels using data from large-scale GWAS of European populations. Female infertility data were sourced from 6,481 cases and 75,450 controls in the FinnGen Consortium. We employed methods including Inverse Variance Weighted (IVW), Weighted Median, and MR-Egger regression to assess causality. Results: We found that elevated SUA levels causally increase the risk of female infertility (IVW OR: 1.13, P=0.047). Elevated SUA levels significantly decrease SHBG levels (ß=-0.261; P=2.177e-04), with SHBG mediating 27.93% of the effect of SUA on infertility (OR=0.854; 95%CI, 0.793-0.920; P=2.853e-05). Additionally, elevated TT levels, which were associated with decreased SUA levels (ß=-0.127), showed an indirect effect on infertility mediated by SUA (ß=-0.0187; 95% CI, -0.041 to -0.003; P=0.046). Conclusion: Our findings demonstrate causal links between high SUA and increased risk of female infertility mediated by hormonal factors such as SHBG and TT. These insights suggest new avenues for infertility treatment and highlight the need for further research into these mechanisms.

Choline consumption reduces CVD risk via body composition modification.

Despite extensive research on the relationship between choline and cardiovascular disease (CVD), conflicting findings have been reported. We aim to investigate the relationship between choline and CVD. Our analysis screened a retrospective cohort study of 14,663 participants from the National Health and Nutrition Examination Survey conducted between 2013 and 2018. Propensity score matching and restricted cubic splines was used to access the association between choline intake and the risk of CVD. A two-sample Mendelian randomization (MR) analysis was conducted to examine the potential causality. Additionally, sets of single cell RNA-sequencing data were extracted and analyzed, in order to explore the role of choline metabolism pathway in the progression and severity of the CVD and the underlying potential mechanisms involved. The adjusted odds ratios and 95% confidence intervals for stroke were 0.72 (0.53-0.98; p = 0.035) for quartile 3 and 0.54 (0.39-0.75; p < 0.001) for quartile 4. A stratified analysis revealed that the relationship between choline intake and stroke varied among different body mass index and waist circumference groups. The results of MR analysis showed that choline and phosphatidylcholine had a predominantly negative causal effect on fat percentage, fat mass, and fat-free mass, while glycine had opposite effects. Results from bioinformatics analysis revealed that alterations in the choline metabolism pathway following stroke may be associated with the prognosis. Our study indicated that the consumption of an appropriate quantity of choline in the diet may help to protect against CVD and the effect may be choline-mediated, resulting in a healthier body composition. Furthermore, the regulation of the choline metabolism pathway following stroke may be a promising therapeutic target.

Molecular characteristics and systemic treatment options of liposarcoma: A systematic review.

Liposarcoma (LPS) is a rare soft tissue sarcoma that develops from the differentiation of fat cells, typically occurring in the lower extremities and retroperitoneal space. Depending on its histological morphology and molecular changes, LPS can be divided into various subtypes, each exhibiting distinct biological behaviors. During treatment, especially for LPS arising in the retroperitoneum, the extent and quality of the initial surgery are critically important. Treatment strategies must be tailored to the specific type of LPS. Over the past few decades, the treatment of LPS has undergone numerous advancements, with new therapeutic approaches such as targeted drugs and immunotherapies continually emerging. This paper reviews the biological characteristics, molecular alterations, as well as surgical and pharmacological treatments of various LPS subtypes, with the aim of enhancing clinicians' understanding and emphasizing the importance of individualized precision therapy. With a deeper understanding of the biological characteristics and molecular alterations of LPS, future treatment trends are likely to focus more on developing personalized treatment plans to better address the various types of LPS.

[Ergosterol peroxide inducing apoptosis of human hepatocellular carcinoma by regulating mitochondrial apoptosis pathway].

This study aims to investigate the effect of ergosterol peroxide(EP) on the apoptosis of human hepatocellular carcinoma and its mechanism of action. The cell viability of HepG2 and SK-Hep-1 cells with 0(blank control), 2.5, 5, 10, 20, 40, and 80 µmol·L~(-1) of EP after 24, 48, and 72 h of action was detected by using CCK-8 assay, and the half inhibitory concentrations(IC_(50)) at 24, 48, and 72 h were calculated. Formal experiments were performed to detect the effect of EP on intracellular reactive oxygen species(ROS) using DCFH-DA staining, the effect of EP on intracellular mitochondrial membrane potential using JC-1 staining, the number of apoptotic cells using Annexin V-FITC/PI double-staining after HepG2 cells were co-cultured with 0(blank control), 10, 20, 40 µmol·L~(-1) EP for 48 h. The effects of EP at different concentrations on apoptotic morphology were detected using AO/EB staining. The effects of different concentrations of EP on the protein expression of mitochondrial apoptosis pathway-related proteins B cell lymphoma 2(Bcl-2), cytochrome C(Cyt-C), Bcl-2-related X protein(Bax), caspase-3, cleaved caspase-3, caspase-9, and cleaved caspase-9 were examined by using Western blot. The results showed that different concentrations of EP could inhibit the proliferation of hepatocellular carcinoma with concentration-and time-dependent trends. Compared with the blank control group, the ROS level in the EP-treated group increased significantly(P<0.05). The mitochondrial membrane potential decreased significantly(P<0.05). The total apoptosis rate increased significantly(P<0.05). The expression of Bcl-2 protein was significantly down-regulated, and the expression of Cyt-C, Bax, cleaved caspase-9, and cleaved caspase-3 were significantly up-regulated(P<0.05). In summary, EP may inhibit the proliferation of hepatocellular carcinoma by modulating the mitochondria-mediated apoptosis pathway and induce apoptosis.

[Mechanism of ergosterol peroxide on MCF-7 breast cancer cells based on network pharmacology and in vitro experiments].

This study investigated the effects of ergosterol peroxide(EP) on the proliferation and apoptosis of MCF-7 breast cancer cells, explored its possible mechanisms of action, and verified the effects and mechanisms by in vitro experiments. Network pharmaco-logy was used to screen the target proteins of EP and construct target networks and protein-protein interaction(PPI) networks to predict the potential target proteins and related pathways involved in EP anti-breast cancer effects. The MTT assay was performed to measure the inhibitory effect of EP on MCF-7 cell proliferation, and the colony formation assay was used to assess the cell cloning ability. Flow cytometry and laser confocal microscopy were employed to evaluate cell apoptosis, mitochondrial membrane potential and reactive oxygen species(ROS) levels. Western blot analysis was conducted to examine the expression levels of B-cell lymphoma 2(Bcl-2), Bcl-2-associated X protein(Bax), cytochrome C(Cyt C), caspase-7, cleaved caspase-7, phosphatidylinositol 3-kinase(PI3K), and se-rine/threonine kinase B(AKT) in MCF-7 cells treated with EP. The results of network pharmacology prediction yielded 173 common targets between EP and breast cancer; the results of Kyoto Encyclopedia of Genes and Genomes(KEGG) enrichment analysis showed that EP treatment for breast cancer mainly affected the signaling pathways such as cancer pathway, PI3K-AKT signaling pathway, cellular senescence signaling pathway, and viral carcinogenesis pathway; and the MTT assay results showed that the viability of MCF-7 cells in the EP group was significantly lower than that in the control group, exhibiting a time-and concentration-dependent trend, and EP can inhibit colony formation of MCF-7 breast cancer cells. Treatment with 10, 20, and 40 µmol·L~(-1) EP for 24 h resulted in a significant increase in the total apoptosis rate of MCF-7 cells, a significant decrease in mitochondrial membrane potential, and a significant increase in ROS levels. In addition, treatment with EP led to an upregulation of Cyt C, Bax, and cleaved caspase-7 protein expression, and a downregulation of p-PI3K, p-AKT, and Bcl-2 protein expression in MCF-7 cells. Studies have shown that EP inhibits MCF-7 breast cancer cell proliferation and reduces colony formation by a mechanism that may be related to the PI3K-AKT pathway mediating the mitochondrial apoptotic pathway.

Neuroendoscopic Parafascicular Evacuation of Spontaneous Intracerebral Hemorrhage (NESICH Technique): A Multicenter Technical Experience with Preliminary Findings.

INTRODUCTION: Intracerebral hemorrhage (ICH) is a severe manifestation of stroke, demonstrating notably elevated global mortality and morbidity. Thus far, effective therapeutic strategies for ICH have proven elusive. Currently, minimally invasive techniques are widely employed for ICH management, particularly using endoscopic hematoma evacuation in cases of deep ICH. Exploration of strategies to achieve meticulous surgery and diminish iatrogenic harm, especially to the corticospinal tract, with the objective of enhancing the neurological prognosis of patients, needs further efforts. METHODS: We comprehensively collected detailed demographic, clinical, radiographic, surgical, and postoperative treatment and recovery data for patients who underwent endoscopic hematoma removal. This thorough inclusion of data intends to offer a comprehensive overview of our technical experience in this study. RESULTS: One hundred fifty-four eligible patients with deep supratentorial intracerebral hemorrhage who underwent endoscopic hematoma removal were included in this study. The mean hematoma volume was 42 ml, with 74 instances of left-sided hematoma and 80 cases of right-sided hematoma. The median Glasgow Coma Scale (GCS) score at admission was 10 (range from 4 to 15), and the median time from symptom onset to surgery was 18 (range 2 to 96) h. The mean hematoma clearance rate was 89%. The rebleeding and mortality rates within 1 month after surgery were 3.2% and 7.8%, respectively. At the 6-month mark, the proportion of patients with modified Rankin Scale (mRS) scores of 0-3 was 58.4%. CONCLUSION: Both the reduction of surgery-related injury and the protection of the residual corticospinal tract through endoscopic hematoma removal may potentially enhance neurological functional outcomes in patients with deep ICH, warranting validation in a forthcoming multicenter clinical study.

The efficacy and safety of Bazi Bushen Capsule in treating premature aging: A randomized, double blind, multicenter, placebo-controlled clinical trial.

PURPOSE: It is unclear whether traditional Chinese patent medicines can resist premature aging. This prospective study investigated the effects of Bazi Bushen Capsule (BZBS) which is a traditional Chinese patent medicine for tonifying the kidney essence on premature senility symptoms and quality of life, telomerase activity and telomere length. STUDY DESIGN AND METHODS: It was a parallel, multicenter, double-blind, randomized, and placebo-controlled trial. Subjects (n = 530) aged 30-78 years were randomized to receive BZBS or placebo capsules 12 weeks. The primary outcome was the clinical feature of change in kidney deficiency for aging evaluation scale (CFCKD-AES) and tilburg frailty indicator (TFI). The secondary outcomes were SF-36, serum sex hormone level, five times sit-to-stand time (FTSST), 6MWT, motor function test-grip strength, balance test, walking speed, muscle mass measurement, telomerase and telomere length. RESULTS: After 12 weeks of treatment, the CFCKD-AES and TFI scores in the BZBS group decreased by 13.79 and 1.50 respectively (6.42 and 0.58 in the placebo group, respectively); The SF-36 in the BZBS group increased by 98.38 (23.79 in the placebo group). The FTSST, motor function test grip strength, balance test, walking speed, and muscle mass in the elderly subgroup were all improved in the BZBS group. The telomerase content in the BZBS group increased by 150.04 ng/ml compared to the placebo group. The fever led one patient in the placebo group to discontinue the trial. One patient in the placebo group withdrew from the trial due to pregnancy. None of the serious AEs led to treatment discontinuation, and 3 AEs (1.14%) were assessed as related to BZBS by the primary investigator. CONCLUSIONS: BZBS can improve premature aging symptoms, frailty scores, and quality of life, as well as improve FTSST, motor function: grip strength, balance test, walking speed, and muscle mass in elderly subgroups of patients, and enhance telomerase activity, but it is not significantly associated with increasing telomere length which is important for healthy aging. TRIAL REGISTRY: https://www.chictr.org.cn/showproj.html?proj=166181.

A Four-Week High-Fat Diet Induces Anxiolytic-like Behaviors through Mature BDNF in the mPFC of Mice.

The effect of a high-fat diet (HFD) on mood is a widely debated topic, with the underlying mechanisms being poorly understood. This study explores the anxiolytic effects of a four-week HFD in C57BL/6 mice. Five-week-old mice were exposed to either an HFD (60% calories from fat) or standard chow diet (CD) for four weeks, followed by cannula implantation, virus infusion, behavioral tests, and biochemical assays. Results revealed that four weeks of an HFD induced anxiolytic-like behaviors and increased the protein levels of mature brain-derived neurotrophic factor (mBDNF) and phosphorylated tyrosine kinase receptor B (p-TrkB) in the medial prefrontal cortex (mPFC). Administration of a BDNF-neutralizing antibody to the mPFC reversed HFD-induced anxiolytic-like behaviors. Elevated BDNF levels were observed in both neurons and astrocytes in the mPFC of HFD mice. Additionally, these mice exhibited a higher number of dendritic spines in the mPFC, as well as upregulation of postsynaptic density protein 95 (PSD95). Furthermore, mRNA levels of the N6-methyladenosine (m6A) demethylase, fat mass and obesity-associated protein (FTO), and the hydrolase matrix metalloproteinase-9 (MMP9), also increased in the mPFC. These findings suggest that an HFD may induce FTO and MMP9, which could potentially regulate BDNF processing, contributing to anxiolytic-like behaviors. This study proposes potential molecular mechanisms that may underlie HFD-induced anxiolytic behaviors.

Identification and validation of anoikis-related genes to clarify the prognosis and immune mechanisms of patients with low-grade glioma.

BACKGROUND: Low-grade glioma (LGG) has an extremely poor prognosis, and the mechanism leading to malignant development has not been determined. The aim of our study was to clarify the function and mechanism of anoikis and TIMP1 in the malignant progression of LGG. METHODS: We screened 7 anoikis-related genes from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases to construct a prognostic-predicting model. The study assessed the clinical prognosis, pathological characteristics, and immune cell infiltration in both high- and low-risk groups. Additionally, the potential modulatory effects of TIMP1 on proliferation, migration, and anoikis in LGG were investigated both in vivo and in vitro. RESULTS: In this study, we identified seven critical genes, namely, PTGS2, CCND1, TIMP1, PDK4, LGALS3, CDKN1A, and CDKN2A. Kaplan‒Meier (K‒M) curves demonstrated a significant correlation between clinical features and overall survival (OS), and single-cell analysis and mutation examination emphasized the heterogeneity and pivotal role of hub gene expression imbalances in LGG development. Immune cell infiltration and microenvironment analysis further elucidated the relationships between key genes and immune cells. In addition, TIMP1 promoted the malignant progression of LGG in both in vitro and in vivo models. CONCLUSIONS: This study confirmed that TIMP1 promoted the malignant progression of LGG by inhibiting anoikis, providing insights into LGG pathogenesis and potential therapeutic targets.

Triple-junction solar cells with cyanate in ultrawide-bandgap perovskites.

Perovskite bandgap tuning without quality loss makes perovskites unique among solar absorbers, offering promising avenues for tandem solar cells1,2. However, minimizing the voltage loss when their bandgap is increased to above 1.90 eV for triple-junction tandem use is challenging3-5. Here we present a previously unknown pseudohalide, cyanate (OCN-), with a comparable effective ionic radius (1.97 Å) to bromide (1.95 Å) as a bromide substitute. Electron microscopy and X-ray scattering confirm OCN incorporation into the perovskite lattice. This contributes to notable lattice distortion, ranging from 90.5° to 96.6°, a uniform iodide-bromide distribution and consistent microstrain. Owing to these effects, OCN-based perovskite exhibits enhanced defect formation energy and substantially decreased non-radiative recombination. We achieved an inverted perovskite (1.93 eV) single-junction device with an open-circuit voltage (VOC) of 1.422 V, a VOC × FF (fill factor) product exceeding 80% of the Shockley-Queisser limit and stable performance under maximum power point tracking, culminating in a 27.62% efficiency (27.10% certified efficiency) perovskite-perovskite-silicon triple-junction solar cell with 1 cm2 aperture area.

Circulating soluble CD30 is associated with renal tertiary lymphoid structures and the progression of IgA nephropathy.

BACKGROUND: Renal tertiary lymphoid structures (TLSs) are involved in renal pathology and prognosis of IgA nephropathy (IgAN). CD30 and its ligands participate in the formation of renal TLSs. However, the relationship between circulating CD30 and renal prognosis is unclear. The objective of this study was to evaluate the relationship between circulating CD30 and prognosis in patients with IgAN. METHODS: We conducted a retrospective study including 351 patients with biopsy proved IgAN. We collected clinical and pathologic features at the time of biopsy and recorded renal follow-up outcomes. Circulating CD30 levels in IgAN patients at the time of biopsy were measured via enzyme-linked immunosorbent assay (ELISA). The association between elevated CD30 levels and the composite endpoint (defined as a ≥ 50 % decline in eGFR from baseline, end-stage renal disease, or death) was investigated using Cox regression analysis. RESULTS: During a median follow-up period of 5.12 years, 44 (12.5 %) patients in the cohort reached the composite endpoint. Kaplan-Meier survival curve analysis revealed a significant association between higher circulating CD30 levels and a poorer renal prognosis (log-rank P < 0.001). Cox regression analysis showed that high CD30 was an independent factor for the composite endpoints in multivariable-adjusted models (HR 3.397, 95 % CI: 1.230-9.384, P = 0.018). These associations were also observed in a subgroup of patients with concomitant renal TLSs formation (10.443, 95 % CI: 1.680-65.545, P = 0.012), proteinuria > 1 g/d (HR 12.287, 95 % CI: 1.499-100.711, P = 0.019), and female patients (HR 22.372, 95 % CI: 1.797-278.520, P = 0.016). CONCLUSION: Elevated level of circulating CD30 is an independent risk factor for renal disease progression in patients with IgAN.

Alkaline-earth ion stabilized sub-nano-platinum tin clusters for propane dehydrogenation.

The strong promotion effects of alkali/alkaline earth metals are frequently reported for heterogeneous catalytic processes such as propane dehydrogenation (PDH), but their functioning principles remain elusive. This paper describes the effect of the addition of calcium (Ca) on reducing the deactivation rate of platinum-tin (Pt-Sn) catalyzed PDH from 0.04 h-1 to 0.0098 h-1 at 873 K under a WHSV of 16.5 h-1 of propane. The Pt-Sn-Ca catalyst shows a high propylene selectivity of >96% with a propylene production rate of 41 molC3H6 (gPt h)-1 and ∼1% activity loss after regeneration. The combination of characterization and DFT simulations reveals that Ca acts as a structural promoter favoring the transition of Snn+ in the parent catalyst to Sn0 during reduction, and the latter is an electron donor that increases the electron density of Pt. This greatly suppresses coke formation from deep dehydrogenation. Moreover, it was found that Ca promotes the formation of a highly reactive and sintering-resistant sub-nano Pt-Sn alloy with a diameter of approximately 0.8 nm. These lead to high activity and selectivity for the Pt-Sn-Ca catalyst for PDH.

IgG antibody response to SARS-CoV-2 infection and its influencing factors in lymphoma patients.

BACKGROUND: The ability of generating effective humoral immune responses to SARS-CoV-2 infection has not been clarified in lymphoma patients. The study aimed to investigate the antibody (Ab) production after SARS-Cov-2 infection and clarify the factors affecting the Ab generation in these patients. PATIENTS & METHODS: 80 lymphoma patients and 51 healthy controls were included in this prospective observational study. Clinical factors and treatment regimens affecting Ab positive rate (APR) and Ab levels were analyzed by univariate and multivariate methods. RESULTS: The anti-SARS-CoV-2 IgG APR and Ab levels in lymphoma patients were significantly lower than those in healthy controls. Lymphoma patients with COVID-19 vaccination had significantly higher APR and Ab levels compared with those without vaccination. Additionally, the use of dexamethasone for COVID-19 treatment had a negative impact on Ab levels. For the impact of treatment regimens on the APR and Ab levels, the results showed that patients treated with ≥ 6 times CD20 monoclonal Ab (mAb) and patients treated with autologous hematopoietic stem cell transplantation (ASCT) prior to infection produced a statistically lower APR and Ab levels compared with those treated with 1-5 times CD20 mAb and those treated without ASCT, respectively. Furthermore, multiple regression analysis indicated that the number of anti-CD20 treatment was an independent predictor for both APR and Ab levels. CONCLUSIONS: Humoral immune response to SARS-CoV-2 infection was impaired in lymphoma patients partly due to anti-CD20 and ASCT treatment. COVID-19 vaccination may be more needed for these patients.

OX40L-expressing M1-like macrophage exosomes for cancer immunotherapy.

With only limited clinical patient benefit, focusing on new immune checkpoint pathways could be an important complement to current immune checkpoint drugs. In addition, not only does T cell-mediated adaptive immunity play an important role, but also macrophage-mediated innate immunity, due to its abundant presence in solid tumors. Here, we developed an engineered M1-like macrophage exosome, OX40L M1-exos. OX40L M1-exos can activate the adaptive immunity by activating the OX40/OX40L pathway and can reprogram M2-like tumor-associated macrophages into M1-like macrophages, thereby restoring and enhancing macrophage-mediated innate immunity. Our OX40L M1-exos achieved an effective synergistic effect of innate and adaptive immunity and achieved a potent therapeutic effect in a mouse breast cancer model, effectively inhibiting tumor growth and metastasis. These results suggest that OX40L M1-exos are an attractive therapeutic strategy and may be an important complement to current cancer immunotherapies.

Current Status and Progress in Stem Cell Therapy for Intracerebral Hemorrhage.

Intracerebral hemorrhage is a highly prevalent and prognostically poor disease, imposing immeasurable harm on human life and health. However, the treatment options for intracerebral hemorrhage are severely limited, particularly in terms of improving the microenvironment of the lesion, promoting neuronal cell survival, and enhancing neural function. This review comprehensively discussed the application of stem cell therapy for intracerebral hemorrhage, providing a systematic summary of its developmental history, types of transplants, transplantation routes, and transplantation timing. Moreover, this review presented the latest research progress in enhancing the efficacy of stem cell transplantation, including pretransplantation preconditioning, genetic modification, combined therapy, and other diverse strategies. Furthermore, this review pioneeringly elaborated on the barriers to clinical translation for stem cell therapy. These discussions were of significant importance for promoting stem cell therapy for intracerebral hemorrhage, facilitating its clinical translation, and improving patient prognosis.