SARS-CoV-2-specific T-cell responses are induced in people living with human immunodeficiency virus after booster vaccination.

BACKGROUND: T-cell-mediated immunity is crucial for the effective clearance of viral infection, but the T-cell-mediated immune responses that are induced by booster doses of inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines in people living with human immunodeficiency virus (PLWH) remain unclear. METHODS: Forty-five PLWH who had received antiretroviral therapy (ART) for more than two years and 29 healthy controls (HCs) at Beijing Youan Hospital were enrolled to assess the dynamic changes in T-cell responses between the day before the third vaccine dose (week 0) and 4 or 12 weeks (week 4 or week 12) after receiving the third dose of inactivated SARS-CoV-2 vaccine. Flow cytometry, enzyme-linked immunospot (ELISpot), and multiplex cytokines profiling were used to assess T-cell responses at the three timepoints in this study. RESULTS: The results of the ELISpot and activation-induced marker (AIM) assays showed that SARS-CoV-2-specific T-cell responses were increased in both PLWH and HCs after the third dose of the inactivated SARS-CoV-2 vaccine, and a similar magnitude of immune response was induced against the Omicron (B.1.1.529) variant compared to the wild-type strain. In detail, spike-specific T-cell responses (measured by the ELISpot assay for interferon γ [IFN-γ] release) in both PLWH and HCs significantly increased in week 4, and the spike-specific T-cell responses in HCs were significantly stronger than those in PLWH 4 weeks after the third vaccination. In the AIM assay, spike-specific CD4+ T-cell responses peaked in both PLWH and HCs in week 12. Additionally, significantly higher spike-specific CD8+ T-cell responses were induced in PLWH than in HCs in week 12. In PLWH, the release of the cytokines interleukin-2 (IL-2), tumour necrosis factor-alpha (TNF-α), and IL-22 by peripheral blood mononuclear cells (PBMCs) that were stimulated with spike peptides increased in week 12. In addition, the levels of IL-4 and IL-5 were higher in PLWH than in HCs in week 12. Interestingly, the magnitude of SARS-CoV-2-specific T-cell responses in PLWH was negatively associated with the extent of CD8+ T-cell activation and exhaustion. In addition, positive correlations were observed between the magnitude of spike-specific T-cell responses (determined by measuring IFN-γ release by ELISpot) and the amounts of IL-4, IL-5, IL-2 and IL-17F. CONCLUSIONS: Our findings suggested that SARS-CoV-2-specific T-cell responses could be enhanced by the booster dose of inactivated COVID-19 vaccines and further illustrate the importance of additional vaccination for PLWH.

Acupuncture combined with mirror therapy for post-stroke dyskinesia: A meta-analysis and systematic review.

BACKGROUND: Dyskinesia is one of the most common complications of stroke. Acupuncture therapy (AT) and mirror therapy (MT) are promising rehabilitation measures for the treatment of post-stroke dyskinesia. Although some studies suggested that AT and MT are effective and safe for dyskinesia, the effects, and safety remain uncertain due to lacking strong evidence. The purpose of this study is to investigate the efficacy and safety of AT combined with MT in the treatment of post-stroke dyskinesia. METHODS: We searched the following databases: PubMed, Web of Science, Cochrane Library, EMBASE, Medline, China Knowledge Network, WANFANG, and China Biomedical Literature Database, from inception to 1 January 2023 to identify eligible studies. Total effective rate, the Fugl-Meyer assessment scale (FMA) upper and lower limb scores, modified Barthel index scores, Berg balance scale, modified Ashworth scale, and adverse reactions were adopted as outcome indicators. The Grading of Recommendations Assessment Development and Evaluation system was used by 2 independent reviewers to assess the quality of evidence for the outcome indicators included in the study. The statistical analysis was conducted by RevMan V.5.4 software. RESULTS: A total of 24 randomized controlled studies included 2133 patients with post-stroke dyskinesia were included. The total effective rate of AT combined with MT was more advantageous in the treatment of post-stroke dyskinesia (relative risk = 1.31, 95% confidence interval [CI] [1.22-1.42], Z = 6.96, P < .0001). AT combined with MT was more advantageous for FMA upper limb score (mean difference [MD] = 6.67, 95% CI [5.21-8.13], Z = 8.97, P < .00001) and FMA lower limb score (MD = 3.72, 95% CI [2.81-4.63], Z = 7.98, P < .00001). Meta-analysis showed that AT combined with MT for post-stroke dyskinesia had a more advantageous modified Barthel index score (MD = 9.51, 95% CI [7.44-11.58], Z = 9.01, P < .00001). CONCLUSION: AT combined with MT is effective in improving motor function and daily living ability of patients, especially in improving muscle spasms. However, these results should be regarded with caution given the low quality of evidence for the evaluation results.

Characterization of prostatic cancer lesion and gleason grade using a continuous-time random-walk diffusion model at high b-values.

Background: Distinguishing between prostatic cancer (PCa) and chronic prostatitis (CP) is sometimes challenging, and Gleason grading is strongly associated with prognosis in PCa. The continuous-time random-walk diffusion (CTRW) model has shown potential in distinguishing between PCa and CP as well as predicting Gleason grading. Purpose: This study aimed to quantify the CTRW parameters (α, ß & Dm) and apparent diffusion coefficient (ADC) of PCa and CP tissues; and then assess the diagnostic value of CTRW and ADC parameters in differentiating CP from PCa and low-grade PCa from high-grade PCa lesions. Study type: Retrospective (retrospective analysis using prospective designed data). Population: Thirty-one PCa patients undergoing prostatectomy (mean age 74 years, range 64-91 years), and thirty CP patients undergoing prostate needle biopsies (mean age 68 years, range 46-79 years). Field strength/Sequence: MRI scans on a 3.0T scanner (uMR790, United Imaging Healthcare, Shanghai, China). DWI were acquired with 12 b-values (0, 50, 100, 150, 200, 500, 800, 1200, 1500, 2000, 2500, 3000 s/mm2). Assessment: CTRW parameters and ADC were quantified in PCa and CP lesions. Statistical tests: The Mann-Whitney U test was used to evaluate the differences in CTRW parameters and ADC between PCa and CP, high-grade PCa, and low-grade PCa. Spearman's correlation of the pathologic grading group (GG) with CTRW parameters and ADC was evaluated. The usefulness of CTRW parameters, ADC, and their combinations (Dm, α and ß; Dm, α, ß, and ADC) to differentiate PCa from CP and high-grade PCa from low-grade PCa was determined by logistic regression and receiver operating characteristic curve (ROC) analysis. Delong test was used to compare the differences among AUCs. Results: Significant differences were found for the CTRW parameters (α, Dm) between CP and PCa (all P<0.001), high-grade PCa, and low-grade PCa (α:P=0.024, Dm:P=0.021). GG is correlated with certain CTRW parameters and ADC(α:P<0.001,r=-0.795; Dm:P<0.001,r=-0.762;ADC:P<0.001,r=-0.790). Moreover, CTRW parameters (α, ß, Dm) combined with ADC showed the best diagnostic efficacy for distinguishing between PCa and CP as well as predicting Gleason grading. The differences among AUCs of ADC, CTRW parameters and their combinations were not statistically significant (P=0.051-0.526). Conclusion: CTRW parameters α and Dm, as well as their combination were beneficial to distinguish between CA and PCa, low-grade PCa and high-grade PCa lesions, and CTRW parameters and ADC had comparable diagnostic performance.

The role of triglyceride-glucose index in the differential diagnosis of atherosclerotic stroke and cardiogenic stroke.

OBJECTIVE: This study aims to investigate the role of the triglyceride glucose (TyG) index in differentiating cardiogenic stroke (CE) from large atherosclerotic stroke (LAA). METHOD: In this retrospective study, patients with acute ischemic stroke were recruited from the First Affiliated Hospital of Soochow University, Lianyungang Second People's Hospital and Lianyungang First People's Hospital. Their general data, medical history and laboratory indicators were collected and TyG index was calculated. Groups were classified by the TyG index quartile to compare the differences between groups. Logistic regression was utilized to assess the relationship between the TyG index and LAA. The receiver operating characteristic curve (ROC) curve was used to evaluate the diagnostic efficiency of the TyG index in differentiating LAA from CE. RESULT: The study recruited 1149 patients. After adjusting for several identified risk factors, groups TyG-Q2, TyG-Q3, and TyG-Q4 had a higher risk of developing LAA compared to group TyG-Q1(odds ratio (OR) = 1.63,95% confidence interval (CI) = 1.11-2.39, OR = 1.72,95%CI = 1.16-2.55, OR = 2.06,95%CI = 1.36-3.09). TyG has certain diagnostic value in distinguishing LAA from CE(AUC = 0.595, 95%CI0.566-0.623;P<0.001). CONCLUSION: Summarily, the TyG index has slight significance in the identification of LAA and CE; it is particularly a marker for their preliminary identification.

Genome-wide profiling of WRKY genes involved in flavonoid biosynthesis in Erigeron breviscapus.

The transcription factors of WRKY genes play essential roles in plant growth, stress responses, and metabolite biosynthesis. Erigeron breviscapus, a traditional Chinese herb, is abundant in flavonoids and has been used for centuries to treat cardiovascular and cerebrovascular diseases. However, the WRKY transcription factors that regulate flavonoid biosynthesis in E. breviscapus remain unknown. In this study, a total of 75 EbWRKY transcription factors were predicted through comprehensive genome-wide characterization of E. breviscapus and the chromosomal localization of each EbWRKY gene was investigated. RNA sequencing revealed transient responses of 74 predicted EbWRKY genes to exogenous abscisic acid (ABA), salicylic acid (SA), and gibberellin 3 (GA3) after 4 h of treatment. In contrast, the expression of key structural genes involved in flavonoid biosynthesis increased after 4 h in GA3 treatment. However, the content of flavonoid metabolites in leaves significantly increased at 12 h. The qRT-PCR results showed that the expression patterns of EbWRKY11, EbWRKY30, EbWRKY31, EbWRKY36, and EbWRKY44 transcription factors exhibited a high degree of similarity to the 11 structural genes involved in flavonoid biosynthesis. Protein-DNA interactions were performed between the key genes involved in scutellarin biosynthesis and candidate WRKYs. The result showed that F7GAT interacts with EbWRKY11, EbWRKY36, and EbWRKY44, while EbF6H has a self-activation function. This study provides comprehensive information on the regulatory control network of flavonoid accumulation mechanisms, offering valuable insights for breeding E. breviscapus varieties with enhanced scutellarin content.

Examining the impact of permissibility hypercapnia on postoperative delirium among elderly patients undergoing thoracoscopic-laparoscopic esophagectomy: A single-center investigative study.

OBJECTIVE: This study explores how permissive hypercapnia, a key aspect of lung protective ventilation, impacts postoperative delirium in elderly patients following thoracic surgery. METHODS: A single-center trial at The Second Hospital of Anhui Medical University involved 136 elderly patients undergoing thoracoscopic esophageal cancer resection. Randomly assigned to maintain PaCO2 35-45 mmHg (group N) or 46-55 mmHg (group H). Primary outcome: postoperative delirium (POD) incidence 1-3 days post-surgery. Secondary endpoints included monitoring rSO2, cardiovascular parameters (MAP, HR), pH, OI, and respiratory parameters (VT, RR, Cdyn, PIP) at specific time points. Perioperative tests assessed CRP/ALB ratio (CAR) and systemic inflammatory index (SII). VAS scores were documented for three postoperative days. RESULTS: Postoperatively, group H showed significantly lower POD incidence than group N (7.4% vs. 19.1%, P = 0.043). Group H exhibited higher PaCO2 and rSO2 during surgery (P < 0.05). Patients in group H maintained better cardiovascular stability with higher blood pressure and lower heart rate on T2-4 (P < 0.05). Respiratory parameters were more stable in group H with lower TV, RR, and PIP, and higher Cdyn during OLV (P < 0.05). Group H had lower pH and OI at T2-4 (P < 0.05). CRP and CAR levels rose less in group H on the first day and one week later (P < 0.05). CONCLUSIONS: Maintaining PaCO2 at 46-55 mmHg reduces POD incidence, possibly by enhancing rSO2 levels and stabilizing intraoperative respiration/circulation.

Lung-intestinal axis, Shuangshen granules attenuate lung metastasis by regulating the intestinal microbiota and related metabolites.

BACKGROUND: Based on the proposed lung-intestinal axis, there is a significant correlation between the microbiota and lung metastasis. Targeting the microbial composition is valuable in modulating the host response to cancer therapeutics. As a traditional Chinese medicine (TCM) formula, Shuangshen granules (SSG) are clinically useful in delaying lung metastasis, but its underlying mechanisms remain unknown. METHODS: The C57BL/6N mice were chosen to establish the Lewis lung cancer models. The broad-spectrum antibiotics (ABX) group was set up to estimate the effect of microbiota composition on metastasis. The therapeutic effects of different doses of SSG in treating lung metastasis were investigated through histopathology, immunohistochemistry, and Western blot analysis methods. Additionally, the phenotype of tumor-associated macrophages (TAMs) in the lung and blood was evaluated by flow cytometry. The fecal microbiota transplantation (FMT) and negative control (ABX plus high dose SSG group) experiments were also designed to assess intestinal microbiota's role in SSG intervention's outcome in lung metastasis. The 16S rRNA amplicon sequencing and Untargeted metabolomic analysis were used to analyze intestinal microbiota and metabolite changes mediated by SSG in tumor-bearing mice with lung metastasis. RESULT: ABX could observably lead to intestinal microbiota dysbiosis and enhance metastasis. SSG showed a significant chemopreventive effect in lung metastasis, reduced metastatic nodules and the expression levels of pre-metastatic niche biomarkers, and enriched the ratio of CD86+F4/80+CD11b+ cells, while FMT delayed metastasis similarly. The analysis of microbiota and metabolites revealed that SSG significantly enriched probiotics in feces, including Akkermansia muciniphila, Lachnoclostridium sp YL32, Limosilactobacillus reuteri, and potential anti-cancer serum metabolites, including Ginsenoside Rb1, Isoquinoline, Betulin and so on. We also investigated the mechanism of SSG protection against lung metastasis and showed that SSG regulated microbiota, improved TAMs polarization, and inhibited the expression of the NF-κB pathway. CONCLUSION: The results presented in our article demonstrated that SSG improved TAMs polarization and inhibited the NF-κB pathway by alleviating intestinal microbiota imbalance and metabolic disorders in tumor-bearing mice, resulting in delayed lung metastasis.

Genomic analysis based on chromosome-level genome assembly reveals Myrtaceae evolution and terpene biosynthesis of rose myrtle.

BACKGROUND: Rose myrtle (Rhodomyrtus tomentosa (Ait.) Hassk), is an evergreen shrub species belonging to the family Myrtaceae, which is enriched with bioactive volatiles (α-pinene and ß-caryophyllene) with medicinal and industrial applications. However, the mechanism underlying the volatile accumulation in the rose myrtle is still unclear. RESULTS: Here, we present a chromosome-level genomic assembly of rose myrtle (genome size = 466 Mb, scaffold N50 = 43.7 Mb) with 35,554 protein-coding genes predicted. Through comparative genomic analysis, we found that gene expansion and duplication had a potential contribution to the accumulation of volatile substances. We proposed that the action of positive selection was significantly involved in volatile accumulation. We identified 43 TPS genes in R. tomentosa. Further transcriptomic and TPS gene family analyses demonstrated that the distinct gene subgroups of TPS may contribute greatly to the biosynthesis and accumulation of different volatiles in the Myrtle family of shrubs and trees. The results suggested that the diversity of TPS-a subgroups led to the accumulation of special sesquiterpenes in different plants of the Myrtaceae family. CONCLUSIONS: The high quality chromosome-level rose myrtle genome and the comparative analysis of TPS gene family open new avenues for obtaining a higher commercial value of essential oils in medical plants.

Efficacy of Voluntary Medical Male Circumcision to Prevent HIV Infection Among Men Who Have Sex With Men : A Randomized Controlled Trial.

BACKGROUND: Observational studies suggest that voluntary medical male circumcision (VMMC) may lower HIV risk among men who have sex with men (MSM). A randomized controlled trial (RCT) is needed to confirm this. OBJECTIVE: To assess the efficacy of VMMC in preventing incident HIV infection among MSM. DESIGN: An RCT with up to 12 months of follow-up. (Chinese Clinical Trial Registry: ChiCTR2000039436). SETTING: 8 cities in China. PARTICIPANTS: Uncircumcised, HIV-seronegative men aged 18 to 49 years who self-reported predominantly practicing insertive anal intercourse and had 2 or more male sex partners in the past 6 months. INTERVENTION: VMMC. MEASUREMENTS: Rapid testing for HIV was done at baseline and at 3, 6, 9, and 12 months. Behavioral questionnaires and other tests for sexually transmitted infections were done at baseline, 6 months, and 12 months. The primary outcome was HIV seroconversion using an intention-to-treat analysis. RESULTS: The study enrolled 124 men in the intervention group and 123 in the control group, who contributed 120.7 and 123.1 person-years of observation, respectively. There were 0 seroconversions in the intervention group (0 infections [95% CI, 0.0 to 3.1 infections] per 100 person-years) and 5 seroconversions in the control group (4.1 infections [CI, 1.3 to 9.5 infections] per 100 person-years). The HIV hazard ratio was 0.09 (CI, 0.00 to 0.81; P = 0.029), and the HIV incidence was lower in the intervention group (log-rank P = 0.025). The incidence rates of syphilis, herpes simplex virus type 2, and penile human papillomavirus were not statistically significantly different between the 2 groups. There was no evidence of HIV risk compensation. LIMITATION: Few HIV seroconversions and limited follow-up period. CONCLUSION: Among MSM who predominantly practice insertive anal intercourse, VMMC is efficacious in preventing incident HIV infection; MSM should be included in VMMC guidelines. PRIMARY FUNDING SOURCE: The National Science and Technology Major Project of China.

Magnetic FNS/MILs nanofibers for highly efficient removal of norfloxacin via adsorption and Fenton-like reaction.

Iron-containing MOFs have attracted extensive interest as promising Fenton-like catalysts. In this work, magnetic Fe3O4 nanofiber (FNS)/MOFs composites with stable structure, included FNS/MIL-88B, FNS/MIL-88A and FNS/MIL-100, were prepared via the in-situ solvothermal method. The surface of the obtained fibers was covered by a dense and continuous MOFs layer, which could effectively solve the agglomeration problem of MOFs powder and improved the catalytic performance. The adsorption and catalytic properties of FNS/MOFs composites were evaluated by removal of norfloxacin. FNS/MIL-88B showed the best performance with a maximum adsorption capacity up to 214.09 mg/g, and could degrade 99% of NRF in 60 min. Meanwhile, FNS/MIL-88B had a saturation magnetization of 20 emu/g, and could be rapidly separated by an applied magnetic field. The self-supported nanofibers allowed the adequate contact between MOFs and pollutants, and promoted the catalytic activity and high stability. We believe that this work provided a new idea for the design and preparation of Fenton-like catalysts especially MOFs composites.

Assessing the effectiveness of spatial PCA on SVM-based decoding of EEG data.

Principal component analysis (PCA) has been widely employed for dimensionality reduction prior to multivariate pattern classification (decoding) in EEG research. The goal of the present study was to provide an evaluation of the effectiveness of PCA on decoding accuracy (using support vector machines) across a broad range of experimental paradigms. We evaluated several different PCA variations, including group-based and subject-based component decomposition and the application of Varimax rotation or no rotation. We also varied the numbers of PCs that were retained for the decoding analysis. We evaluated the resulting decoding accuracy for seven common event-related potential components (N170, mismatch negativity, N2pc, P3b, N400, lateralized readiness potential, and error-related negativity). We also examined more challenging decoding tasks, including decoding of face identity, facial expression, stimulus location, and stimulus orientation. The datasets also varied in the number and density of electrode sites. Our findings indicated that none of the PCA approaches consistently improved decoding performance related to no PCA, and the application of PCA frequently reduced decoding performance. Researchers should therefore be cautious about using PCA prior to decoding EEG data from similar experimental paradigms, populations, and recording setups.

Multifunctional Self-Signaling nanoMIP and Its Application for a Washing-Free Assay of Human Angiotensin-Converting Enzyme 2.

Molecular imprinting techniques have attracted a lot of attention as a potential biomimetic technology, but there are still challenges in protein imprinting. Herein, multifunctional nanosized molecularly imprinted polymers (nanoMIPs) for human angiotensin-converting enzyme 2 (ACE2) were prepared by epitope imprinting of magnetic nanoparticles-anchored peptide (magNP-P) templates, which were further applied to construct a competitive displacement fluorescence assay toward ACE2. A cysteine-flanked dodecapeptide sequence was elaborately selected as an epitope for ACE2, which was immobilized onto the surface of magnetic nanoparticles and served as a magNP-P template for imprinting. During polymerization, fluorescent monomers were introduced to endow fluorescence responsiveness to the prepared self-signaling nanoMIPs. A competitive displacement fluorescence assay based on the nanoMIPs was established and operated in a washing-free manner, yielding a wide range for ACE2 (0.1-6.0 pg/mL) and a low detection limit (0.081 pg/mL). This approach offers a promising avenue in the preparation of nanoMIPs for macromolecule recognition and expands potential application of an MIP in the detection of proteins as well as peptides.

Promiscuous Oxidosqualene Cyclases from Neoalsomitra integrifoliola Catalyzing the Formation of Tetracyclic, Pentacyclic, and Heterocyclic Triterpenes.

Six oxidosqualene cyclases (NiOSC1-NiOSC6) from Neoalsomitra integrifoliola were characterized for the biosynthesis of diverse triterpene scaffolds, including tetracyclic and pentacyclic triterpenes from the 2,3-oxidosqualene (1) and oxacyclic triterpenes from the 2,3:22,23-dioxidosqualene (2). NiOSC1 showed high efficiency in the production of naturally rare (20R)-epimers of oxacyclic triterpenes. Mutagenesis results revealed that the NiOSC1-F731G mutant significantly increased the yields of (20R)-epimers compared to the wild type. Homology modeling and molecular docking elucidated the origin of the (20R)-configuration in the epoxide addition step.

Chemical composition and antioxidant activity of Polygonatum kingianum processed by the traditional method of "Nine Cycles of Steaming and Sun-Drying".

Polygonatum kingianum Coll. et (Hemsl) is a famous Chinese traditional food and medicine analogous plant. The rhizome of P. kingianum showed a decrease in levels of alkaloids, amino acids and derivatives, terpenoids, and an increase in organic acid and saccharides when it was processed by the traditional method of "Nine Cycles of Steaming and Sun-Drying". The relative content of 341 metabolites were increased (fold change, FC > 2; variable importance in projection, VIP > 1 and P-value, P < 0.05); while 456 metabolites were decreased (FC < 0.5, VIP > 1, and P < 0.05). The changes in chemical components result in a decrease in numb taste and an increase in sweetness. The increased antioxidant activity was observed in the processed samples. Together, this work has advanced the mechanism of reducing numb taste and enhancing antioxidant activity in the resource plants, such as P. kingianum, processed by the traditional method.

Response of soil erosion resistance to straw incorporation amount in the black soil region of Northeast China.

Straw incorporation has been considered as an effective environmental management application to improve soil erosion resistance (SER) and organic carbon sequestration. SER is useful to evaluate soil erosion subjected to concentrated flow. Nevertheless, few studies have been performed to examine how SER varied with the amount of straw incorporation on sloping croplands in high latitude and cool regions. In the current study, the fixed bed scouring tests were conducted in a large hydraulic flume using undisturbed soil samples taken from Hebei small watershed in the black soil region of Northeast China. The response of SER to different straw incorporation amounts (0, 1.125, 2.25, 4.5, 6.75, 9.0 and 13.5 t ha-1) was quantified after three months of straw decomposition. The major influencing factors and the corresponding mechanisms were determined. The findings demonstrated that rill erodibility firstly decreased exponentially with straw incorporation amount (R2 = 0.93), while it slightly increased when straw incorporation amount was more than 9.0 t ha-1. Critical shear stress firstly increased logarithmically (R2 = 0.90) and then slightly decreased when the amount exceeded 9.0 t ha-1. Compared to the treatment of 0 t ha-1, rill erodibility reduced by 17.0%-92.8% and critical shear stress increased by 59.6%-127.2% across different treatments of straw incorporation. Rill erodibility had significant and negative correlations with soil organic matter content, aggregate stability, cohesion, root mass density, straw mass density and straw decomposition amount. The key mechanisms for promoting SER were derived by the direct and indirect effects of straw incorporation and its decomposition on soil physicochemical properties and crop roots. The amount of 9.0 t ha-1 was recommended as the optimum amount of straw incorporation in croplands in Northeast China. These findings are useful to understand how soil erosion resistance responds to the amount of straw incorporation and make rational environmental management policy for semi-humid and cool regions.

ALDH2 as an immunological and prognostic biomarker: Insights from pan-cancer analysis.

Aldehyde dehydrogenase 2 (ALDH2) plays a critical role in safeguarding cells against acetaldehyde toxicity and is closely linked to human metabolism. Nevertheless, the involvement of ALDH2 in cancer remains enigmatic. This investigation seeks to comprehensively assess ALDH2's significance in pan-cancer. We conducted an all-encompassing analysis of pan-cancer utilizing multiple databases, including TCGA, linkedomicshs, UALCAN, and Kaplan-Meier plotter. We employed diverse algorithms such as EPIC, MCPCOUNTER, TIDTIMER, xCell, MCP-counter, CIBERSORT, quanTIseq, and EPIC to examine the connection between ALDH2 expression and immune cell infiltration. Single-cell sequencing analysis furnished insights into ALDH2's functional status in pan-cancer. Immunohistochemical staining was performed to validate ALDH2 expression in cancer tissues. In a comprehensive assessment, we observed that tumor tissues demonstrated diminished ALDH2 expression levels compared to normal tissues across 16 different cancer types. ALDH2 expression exhibited a significant positive correlation with the infiltration of immune cells, including CD4 + T cells, CD8 + T cells, neutrophils, B cells, and macrophages, in various tumor types. Moreover, this study explored the association between ALDH2 and patient survival, examined the methylation patterns of ALDH2 in normal and primary tumor tissues, and delved into genetic variations and mutations of ALDH2 in tumors. The findings suggest that ALDH2 could serve as a valuable prognostic biomarker in pan-cancer, closely linked to the tumor's immune microenvironment.

Biosynthetic pathway of prescription cucurbitacin IIa and high-level production of key triterpenoid intermediates in engineered yeast and tobacco.

Cucurbitacin IIa is a triterpenoid isolated exclusively from Hemsleya plants and a non-steroidal anti-inflammatory drug that functions as the main ingredient of prescription Hemslecin capsules and tablets in China. Synthetic biology provides new strategies for production of such valuable cucurbitacins at a large scale; however, the biosynthetic pathway of cucurbitacin IIa has been unknown, and the heterologous production of cucurbitacins in galactose medium has been expensive and low yielding. In this study, we characterized the functions of genes encoding two squalene epoxidases (HcSE1-2), six oxidosqualene cyclases (HcOSC1-6), two CYP450s (HcCYP87D20 and HcCYP81Q59), and an acyltransferase (HcAT1) in cucurbitacin IIa biosynthesis by heterologous expression in Saccharomyces cerevisiae and Nicotiana benthamiana. We achieved high-level production of the key cucurbitacin precursor 11-carbonyl-20ß-hydroxy-Cuol from glucose in yeast via modular engineering of the mevalonate pathway and optimization of P450 expression levels. The resulting yields of 46.41 mg/l 11-carbonyl-20ß-hydroxy-Cuol and 126.47 mg/l total cucurbitacin triterpenoids in shake flasks are the highest yields yet reported from engineered microbes. Subsequently, production of 11-carbonyl-20ß-hydroxy-Cuol by transient gene expression in tobacco resulted in yields of 1.28 mg/g dry weight in leaves. This work reveals the key genes involved in biosynthesis of prescription cucurbitacin IIa and demonstrates that engineered yeast cultivated with glucose can produce high yields of key triterpenoid intermediates. We describe a low-cost and highly efficient platform for rapid screening of candidate genes and high-yield production of pharmacological triterpenoids.

Immune modulation in malignant pleural effusion: from microenvironment to therapeutic implications.

Immune microenvironment and immunotherapy have become the focus and frontier of tumor research, and the immune checkpoint inhibitors has provided novel strategies for tumor treatment. Malignant pleural effusion (MPE) is a common end-stage manifestation of lung cancer, malignant pleural mesothelioma and other thoracic malignancies, which is invasive and often accompanied by poor prognosis, affecting the quality of life of affected patients. Currently, clinical therapy for MPE is limited to pleural puncture, pleural fixation, catheter drainage, and other palliative therapies. Immunization is a new direction for rehabilitation and treatment of MPE. The effusion caused by cancer cells establishes its own immune microenvironment during its formation. Immune cells, cytokines, signal pathways of microenvironment affect the MPE progress and prognosis of patients. The interaction between them have been proved. The relevant studies were obtained through a systematic search of PubMed database according to keywords search method. Then through screening and sorting and reading full-text, 300 literatures were screened out. Exclude irrelevant and poor quality articles, 238 literatures were cited in the references. In this study, the mechanism of immune microenvironment affecting malignant pleural effusion was discussed from the perspectives of adaptive immune cells, innate immune cells, cytokines and molecular targets. Meanwhile, this study focused on the clinical value of microenvironmental components in the immunotherapy and prognosis of malignant pleural effusion.