Structure and distinct supramolecular organization of a PSII-ACPII dimer from a cryptophyte alga Chroomonas placoidea.

Cryptophyte algae are an evolutionarily distinct and ecologically important group of photosynthetic unicellular eukaryotes. Photosystem II (PSII) of cryptophyte algae associates with alloxanthin chlorophyll a/c-binding proteins (ACPs) to act as the peripheral light-harvesting system, whose supramolecular organization is unknown. Here, we purify the PSII-ACPII supercomplex from a cryptophyte alga Chroomonas placoidea (C. placoidea), and analyze its structure at a resolution of 2.47 Å using cryo-electron microscopy. This structure reveals a dimeric organization of PSII-ACPII containing two PSII core monomers flanked by six symmetrically arranged ACPII subunits. The PSII core is conserved whereas the organization of ACPII subunits exhibits a distinct pattern, different from those observed so far in PSII of other algae and higher plants. Furthermore, we find a Chl a-binding antenna subunit, CCPII-S, which mediates interaction of ACPII with the PSII core. These results provide a structural basis for the assembly of antennas within the supercomplex and possible excitation energy transfer pathways in cryptophyte algal PSII, shedding light on the diversity of supramolecular organization of photosynthetic machinery.

Zwitterion-Modified MXene Quantum Dot as a Nanocarrier for Traditional Chinese Medicine Sanguinarine Delivery and Its Application for Photothermal-Chemotherapy Synergistic Antibacterial and Wound Healing.

The nanomaterialization of traditional Chinese medicine (TCM) has aroused widespread interest among researchers. Sanguinarine (SAN) is a kind of TCM with good antibacterial properties, which has important applications in anti-infection of wounds. Additionally, the combination of photothermal therapy and chemotherapy can overcome bacterial resistance, further improving bactericidal and wound healing efficiency. In this paper, we prepared an antibacterial agent by loading SAN on the zwitterion-modified MXene quantum dot nanocarrier (SAN@AHEP@Ta4C3), realizing pH/NIR controlled drug release and photothermal/chemotherapy synergistic antibacterial and wound healing. The particle size of SAN@AHEP@Ta4C3 is about 120 nm, and it has a good water solubility and stability. In addition, it also has excellent photothermal conversion performance (η = 39.2%), which can effectively convert light energy into heat energy under near-infrared (NIR) laser irradiation, further promoting drug release and achieving bactericidal effects by synergistic chemotherapy and photothermal therapy. The in vitro and in vivo experiments show that SAN@AHEP@Ta4C3 exhibits an excellent antibacterial effect against Staphylococcus aureus and Escherichia coli, and it can effectively promote the wound healing of mice. Moreover, the SAN@AHEP@Ta4C3 also has good biocompatibility and has no side effects on normal tissue and organs. This work introduces a multifunctional antibacterial agent based on TCM and hot-spot material MXene, which will have considerable application prospects in biomedical fields.

Efficient Solvent-Free Synthesis of Indolizines Using CuBr Catalyst from Pyridine, Acetophenone, and Electron-Deficient Alkenes.

Herein, we have developed a new approach for the synthesis of indolizine via Cu-catalyzed reaction of pyridine, acetophenone, and nitroolefin under mild conditions in high yields. This reaction involved the formation of C-N and C-C bonds and new indolizine compounds with high stereoselectivity and excellent functional group tolerance.

Quantitative proteomic analysis reveals functional alterations of the peripheral immune system in colorectal cancer.

Colorectal cancer (CRC) is characterized by high morbidity, high mortality, and limited response to immunotherapies. The peripheral immune system is an important component of tumor immunity, and enhancements of peripheral immunity help to suppress tumor progression. However, the functional alterations of the peripheral immune system in CRC are unclear. Here, we used mass spectrometry-based quantitative proteomics to establish a protein expression atlas for the peripheral immune system in CRC, including plasma and five types of immune cells (CD4+ T cells, CD8+ T cells, monocytes, natural killer cells, and B cells). Synthesizing the results of the multidimensional analysis, we observed an enhanced inflammatory phenotype in CRC, including elevated expression of plasma inflammatory proteins, activation of the inflammatory pathway in monocytes, and increased inflammation-related ligand-receptor interactions. Notably, we observed tumor effects on peripheral T cells, including altered cell subpopulation ratios and suppression of cell function. Suppression of CD4+ T cell function is mainly mediated by high expression levels of protein tyrosine phosphatases. Among them, the expression of protein tyrosine phosphatase receptor type J (PTPRJ) gradually increased with CRC progression; knockdown of PTPRJ in vitro could promote T cell activation, thereby enhancing peripheral immunity. We also found that the combination of leucine-rich α-2 glycoprotein 1 (LRG1) and apolipoprotein A4 (APOA4) had the best predictive ability for colorectal cancer and has the potential to be a biomarker. Overall, this study provides a comprehensive understanding of the peripheral immune system in CRC. It also offers insights regarding the potential clinical utilities of these peripheral immune characteristics as diagnostic indicators and therapeutic targets.

Impact of intraoperative dexmedetomidine on postoperative delirium and pro-inflammatory cytokine levels in elderly patients undergoing thoracolumbar compression fracture surgery: A prospective, randomized, placebo-controlled clinical trial.

BACKGROUND: This study evaluates the efficacy of dexmedetomidine (DEX) in reducing postoperative delirium (POD) and modulating pro-inflammatory cytokines in elderly patients undergoing thoracolumbar compression fracture surgery. METHODS: In this randomized, double-blind, placebo-controlled trial conducted from October 2022 to January 2023 at Anting Hospital in Shanghai, 218 elderly patients were randomized into DEX (n = 110) and normal saline (NS, n = 108) groups. The DEX group received 0.5 µg/kg/h DEX, and delirium incidence was assessed using the Confusion Assessment Method (CAM) on days 1 to 3 post-surgery. Levels of interleukins IL-1ß, IL-6, and tumor necrosis factor-α (TNF-α) were measured pre-operation (T0) and on postoperative days 1 (T1) and 3 (T3). Preoperative (T0) and postoperative day 1 (T1) cerebrospinal fluid (CSF) samples were treated with varying concentrations of olanzapine or DEX to observe their regulatory effects on the expression of Phospho-ERK1/2 and Phospho-JNK. RESULTS: Dexmedetomidine significantly lowered the incidence of POD to 18.2%, compared to 30.6% in the NS group (P = .033). While all patients showed an initial increase in cytokine levels after surgery, by T3, IL-6 and TNF-α levels notably decreased in the DEX group, with no significant change in IL-1ß levels across groups. The adverse events rate was similar between groups, demonstrating the safety of DEX in this population. In postoperative CSF samples, treatment with 0.5 mM DEX significantly downregulated Phospho-JNK and upregulated Phospho-ERK1/2 expression, demonstrating a dose-dependent modulation of inflammatory responses. CONCLUSION: Dexmedetomidine is effective in reducing early POD in elderly patients post-thoracolumbar compression fracture surgery. It also decreases IL-6 and TNF-α levels, indicating its potential in managing postoperative inflammatory responses. Treatment with 0.5 mM DEX significantly modulated Phospho-ERK1/2 and Phospho-JNK expressions in postoperative CSF samples, indicating a dose-dependent effect on reducing inflammation. This study contributes to understanding DEX's role in improving postoperative outcomes in elderly patients.

Nanoarchitectonic Engineering of Thermal-Responsive Magnetic Nanorobot Collectives for Intracranial Aneurysm Therapy.

Stent-assisted coiling is a main treatment modality for intracranial aneurysms (IAs) in clinics, but critical challenges remain to be overcome, such as exogenous implant-induced stenosis and reliance on antiplatelet agents. Herein, an endovascular approach is reported for IA therapy without stent grafting or microcatheter shaping, enabled by active delivery of thrombin (Th) to target aneurysms using innovative phase-change material (PCM)-coated magnetite-thrombin (Fe3O4-Th@PCM) FTP nanorobots. The nanorobots are controlled by an integrated actuation system of dynamic torque-force hybrid magnetic fields. With robust intravascular navigation guided by real-time ultrasound imaging, nanorobotic collectives can effectively accumulate and retain in model aneurysms constructed in vivo, followed by controlled release of the encapsulated Th for rapid occlusion of the aneurysm upon melting the protective PCM (thermally responsive in a tunable manner) through focused magnetic hyperthermia. Complete and stable aneurysm embolization is confirmed by postoperative examination and 2-week postembolization follow-up using digital subtraction angiography (DSA), contrast-enhanced ultrasound (CEUS), and histological analysis. The safety of the embolization therapy is assessed through biocompatibility evaluation and histopathology assays. This strategy, seamlessly integrating secure drug packaging, agile magnetic actuation, and clinical interventional imaging, avoids possible exogenous implant rejection, circumvents cumbersome microcatheter shaping, and offers a promising option for IA therapy.

Developing a Cost-Effective Surgical Scheduling System Applying Lean Thinking and Toyota's Methods for Surgery-Related Big Data for Improved Data Use in Hospitals: User-Centered Design Approach.

BACKGROUND: Surgical scheduling is pivotal in managing daily surgical sequences, impacting patient experience and hospital resources significantly. With operating rooms costing approximately US $36 per minute, efficient scheduling is vital. However, global practices in surgical scheduling vary, largely due to challenges in predicting individual surgeon times for diverse patient conditions. Inspired by the Toyota Production System's efficiency in addressing similar logistical challenges, we applied its principles as detailed in the book "Lean Thinking" by Womack and Jones, which identifies processes that do not meet customer needs as wasteful. This insight is critical in health care, where waste can compromise patient safety and medical quality. OBJECTIVE: This study aims to use lean thinking and Toyota methods to develop a more efficient surgical scheduling system that better aligns with user needs without additional financial burdens. METHODS: We implemented the 5 principles of the Toyota system: specifying value, identifying the value stream, enabling flow, establishing pull, and pursuing perfection. Value was defined in terms of meeting the customer's needs, which in this context involved developing a responsive and efficient scheduling system. Our approach included 2 subsystems: one handling presurgery patient data and another for intraoperative and postoperative data. We identified inefficiencies in the presurgery data subsystem and responded by creating a comprehensive value stream map of the surgical process. We developed 2 Excel (Microsoft Corporation) macros using Visual Basic for Applications. The first calculated average surgery times from intra- or postoperative historic data, while the second estimated surgery durations and generated concise, visually engaging scheduling reports from presurgery data. We assessed the effectiveness of the new system by comparing task completion times and user satisfaction between the old and new systems. RESULTS: The implementation of the revised scheduling system significantly reduced the overall scheduling time from 301 seconds to 261 seconds (P=.02), with significant time reductions in the revised process from 99 seconds to 62 seconds (P<.001). Despite these improvements, approximately 21% of nurses preferred the older system for its familiarity. The new system protects patient data privacy and streamlines schedule dissemination through a secure LINE group (LY Corp), ensuring seamless flow. The design of the system allows for real-time updates and has been effectively monitoring surgical durations daily for over 3 years. The "pull" principle was demonstrated when an unplanned software issue prompted immediate, user-led troubleshooting, enhancing system reliability. Continuous improvement efforts are ongoing, except for the preoperative patient confirmation step, which requires further enhancement to ensure optimal patient safety. CONCLUSIONS: Lean principles and Toyota's methods, combined with computer programming, can revitalize surgical scheduling processes. They offer effective solutions for surgical scheduling challenges and enable the creation of a novel surgical scheduling system without incurring additional costs.

Ultrafast Energy Transfer in a Diatom Photosystem II Supercomplex.

The light-harvesting complexes (LHCs) of diatoms, specifically fucoxanthin-Chl a/c binding proteins (FCPs), exhibit structural and functional diversity, as highlighted by recent structural studies of photosystem II-FCP (PSII-FCPII) supercomplexes from different diatom species. The excitation dynamics of PSII-FCPII supercomplexes isolated from the diatom Thalassiosira pseudonana was explored using time-resolved fluorescence spectroscopy and two-dimensional electronic spectroscopy at room temperature and 77 K. Energy transfer between FCPII and PSII occurred remarkably fast (<5 ps), emphasizing the efficiency of FCPII as a light-harvesting antenna. The presence of long-wavelength chlorophylls may further help concentrate excitations in the core complex and increase the efficiency of light harvesting. Structure-based calculations reveal remarkably strong excitonic couplings between chlorophylls in the FCP antenna and between FCP and the PSII core antenna that are the basis for the rapid energy transfer.

Pollution Characteristics and Risk Assessment of Heavy Metals in the Sediments of the Inflow Rivers of Dianchi Lake, China.

To explore the contamination status and identify the source of the heavy metals in the sediments in the major inflow rivers of Dianchi Lake in China, sediment samples were collected and analyzed. Specifically, the distribution, source, water quality, and health risk assessment of the heavy metals were analyzed using correlation analysis (CA), principal component analysis (PCA), the heavy metal contamination factor (Cf), the pollution load index (PLI), and the potential ecological risk index (PERI). Additionally, the chemical fractions were analyzed for mobility characteristics. The results indicate that the average concentration of the heavy metals in the sediment ranked in the descending order of Zn > Cr > Cu > Pb > As > Ni > Cd > Hg, and most of the elements existed in less-mobile forms. The Cfwas in the order of Hg > Zn > Cd > As > Pb > Cr > Ni; the accumulation of Hg, Zn, Cd, and As was obvious. Although the spatial variability of the heavy metal contents was pronounced, the synthetical evaluation index of the PLI and PERI both reached a high pollution level. The PCA and CA results indicate that industrial, transportation, and agricultural emissions were the dominant factors causing heavy metal pollution. These results provide important data for improving water resource management efficiency and heavy metal pollution prevention in Dianchi Lake.

Responses to phytoplankton community succession and expression of key functional genes in plateau lakes under 17ß-estradiol interference.

Steroid estrogens (SEs) have garnered global attention because of their potential hazards to human health and aquatic organisms at low concentrations (ng/L). The ecosystems of plateau freshwater lakes are fragile, the water lag time is long, and pollutants easily accumulate, making them more vulnerable to the impact of SEs. However, the knowledge of the impact of SEs on the growth and decomposition of phytoplankton communities in plateau lakes and the eutrophication process is limited. This study investigated the effects and mechanisms of SEs exposure on dominant algal communities and the expression of typical algal functional genes in Erhai Lake using indoor simulations and molecular biological methods. The results showed that phytoplankton were sensitive to 17ß-estradiol (E2ß) pollution, with a concentration of 50, and 100 ng/L E2ß exposure promoting the growth of cyanophyta and chlorophyta in the short term; this poses an ecological risk of inducing algal blooms. E2ß of 1000 ng/L exposure led to cross-effects of estrogenic effects and toxicity, with most phytoplankton being inhibited. However, small filamentous cyanobacteria and diatoms exhibited greater tolerance; Melosira sp. even exhibited "low inhibition, high promotion" behavior. Exposure to E2ß reduced the Shannon-Wiener diversity index (H'), Pielou index (J), and the number of dominant algal species (S) in phytoplankton communities, leading to instability in community succession. E2ß of 50 ng/L enhanced the expression levels of relevant functional genes, such as ftsH, psaB, atpB, and prx, related to Microcystis aeruginosa. E2ß of 50 ng/L and 5 mg/L can promote the transcription of Microcystis toxins (MC) related genes (mcyA), leading to more MC production by algal cells.

Oral mitochondrial transplantation using nanomotors to treat ischaemic heart disease.

Mitochondrial transplantation is an important therapeutic strategy for restoring energy supply in patients with ischaemic heart disease (IHD); however, it is limited by the invasiveness of the transplantation method and loss of mitochondrial activity. Here we report successful mitochondrial transplantation by oral administration for IHD therapy. A nitric-oxide-releasing nanomotor is modified on the mitochondria surface to obtain nanomotorized mitochondria with chemotactic targeting ability towards damaged heart tissue due to nanomotor action. The nanomotorized mitochondria are packaged in enteric capsules to protect them from gastric acid erosion. After oral delivery the mitochondria are released in the intestine, where they are quickly absorbed by intestinal cells and secreted into the bloodstream, allowing delivery to the damaged heart tissue. The regulation of disease microenvironment by the nanomotorized mitochondria can not only achieve rapid uptake and high retention of mitochondria by damaged cardiomyocytes but also maintains high activity of the transplanted mitochondria. Furthermore, results from animal models of IHD indicate that the accumulated nanomotorized mitochondria in the damaged heart tissue can regulate cardiac metabolism at the transcriptional level, thus preventing IHD progression. This strategy has the potential to change the therapeutic strategy used to treat IHD.

HEMAsNet: A Hemisphere Asymmetry Network Inspired by the Brain for Depression Recognition From Electroencephalogram Signals.

Depression is a prevalent mental disorder that affects a significant portion of the global population. Despite recent advancements in EEG-based depression recognition models rooted in machine learning and deep learning approaches, many lack comprehensive consideration of depression's pathogenesis, leading to limited neuroscientific interpretability. To address these issues, we propose a hemisphere asymmetry network (HEMAsNet) inspired by the brain for depression recognition from EEG signals. HEMAsNet employs a combination of multi-scale Convolutional Neural Network (CNN) and Long Short-Term Memory (LSTM) blocks to extract temporal features from both hemispheres of the brain. Moreover, the model introduces a unique 'Callosum- like' block, inspired by the corpus callosum's pivotal role in facilitating inter-hemispheric information transfer within the brain. This block enhances information exchange between hemispheres, potentially improving depression recognition accuracy. To validate the performance of HEMAsNet, we first confirmed the asymmetric features of frontal lobe EEG in the MODMA dataset. Subsequently, our method achieved a depression recognition accuracy of 0.8067, indicating its effectiveness in increasing classification performance. Furthermore, we conducted a comprehensive investigation from spatial and frequency perspectives, demonstrating HEMAsNet's innovation in explaining model decisions. The advantages of HEMAsNet lie in its ability to achieve more accurate and interpretable recognition of depression through the simulation of physiological processes, integration of spatial information, and incorporation of the Callosum- like block.

Engineered Nanoporous Frameworks for Adsorption Cooling Applications.

The energy demand for traditional vapor-compressed technology for space cooling continues to soar year after year due to global warming and the increasing human population's need to improve living and working conditions. Thus, there is a growing demand for eco-friendly technologies that use sustainable or waste energy resources. This review discusses the properties of various refrigerants used for adsorption cooling applications followed by a brief discussion on the thermodynamic cycle. Next, sorbents traditionally used for cooling are reviewed to emphasize the need for advanced capture materials with superior properties to improve refrigerant sorption. The remainder of the review focus on studies using engineered nanoporous frameworks (ENFs) with various refrigerants for adsorption cooling applications. The effects of the various factors that play a role in ENF-refrigerant pair selection, including pore structure/dimension/shape, morphology, open-metal sites, pore chemistry and possible presence of defects, are reviewed. Next, in-depth insights into the sorbent-refrigerant interaction, and pore filling mechanism gained through a combination of characterization techniques and computational modeling are discussed. Finally, we outline the challenges and opportunities related to using ENFs for adsorption cooling applications and provide our views on the future of this technology.

Gastric Cancer Immune Subtypes and Prognostic Modeling: Insights from Aging-Related Gene Analysis.

Gastric cancer (GC) is highly heterogeneous and influenced by aging-related factors. This study aimed to improve individualized prognostic assessment of GC by identifying aging-related genes and subtypes. Immune scores of GC samples from GEO and TCGA databases were calculated using ESTIMATE and scored as high immune (IS_high) and low immune (IS_low). ssGSEA was used to analyze immune cell infiltration. Univariate Cox regression was employed to identify prognosis-related genes. LASSO regression analysis was used to construct a prognostic model. GSVA enrichment analysis was applied to determine pathways. CCK-8, wound healing, and Transwell assays tested the proliferation, migration, and invasion of the GC cell line (AGS). Cell cycle and aging were examined using flow cytometry, ß-galactosidase staining, and Western blotting. Two aging-related GC subtypes were identified. Subtype 2 was characterized as lower survival probability and higher risk, along with a more immune-responsive tumor microenvironment. Three genes (IGFBP5, BCL11B, and AKR1B1) screened from aging-related genes were used to establish a prognosis model. The AUC values of the model were greater than 0.669, exhibiting strong prognostic value. In vitro, IGFBP5 overexpression in AGS cells was found to decrease viability, migration, and invasion, alter the cell cycle, and increase aging biomarkers (SA-ß-galactosidase, p53, and p21). This analysis uncovered the immune characteristics of two subtypes and aging-related prognosis genes in GC. The prognostic model established for three aging-related genes (IGFBP5, BCL11B, and AKR1B1) demonstrated good prognosis performance, providing a foundation for personalized treatment strategies aimed at GC.

A magnetic calcium phosphate for selective capture of multi-phosphopeptides.

The specific enrichment of multi-phosphopeptides in the presence of non-phosphopeptides and mono-phosphopeptides was still a challenge for phosphoproteomics research. Most of these enrichment materials relied on Zn, Ti, Sn, and other rare precious metals as the bonding center to enrich multi-phosphopeptides while ignoring the use of common metal elements. The addition of rare metals increased the cost of the experiment, which was not conducive to their large-scale application in biomedical proteomics laboratories. In addition, multiple high-speed centrifugation steps also resulted in the loss of low-abundance multi-phosphopeptides in the treatment procedure of biological samples. This study proposed the use of calcium, a common element, as the central bonding agent for synthesizing magnetic calcium phosphate materials (designated as CaP-Fe3O4). These materials aim to capture multi-phosphopeptides and identifying phosphorylation sites. The current results demonstrate that CaP-Fe3O4 exhibited excellent selection specificity, high sensitivity, and stability in the enrichment of multi-phosphopeptides and the identification of phosphorylation sites. Additionally, the introduction of magnetic separation not only reduced the time required for multi-phosphopeptides enrichment but also prevented the loss of these peptides during high-speed centrifugation. These findings contribute to the widespread application and advancement of phosphoproteomics research.

Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: A multicenter, double-blind, placebo-controlled, randomized trial.

BACKGROUND: Yiqi Peiyuan (YQPY) prescription, a composite prescription of traditional Chinese medicine, has been used to prevent or delay the continued deterioration of renal function after acute kidney injury (AKI) in some institutions and has shown considerable efficacy. OBJECTIVE: This is the first randomized controlled trial to assess efficacy and safety of YQPY for improving short-term prognosis in adult patients with AKI. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: This is a prospective, double-blind, multicenter, randomized, and placebo-controlled clinical trial. A total of 144 enrolled participants were randomly allocated to two groups according to a randomization schedule. Participants, caregivers and investigators assessing the outcomes were blinded to group assignment. Patients in the YQPY group received 36 g YQPY granules twice a day for 28 days. Patients in the placebo group received a placebo in the same dose as the YQPY granules. MAIN OUTCOME MEASURES: The primary outcome was the change in the estimated glomerular filtration rate (eGFR) between baseline and after 4 and 24 weeks of treatment. The secondary outcomes were the change of serum creatinine (Scr) level between baseline and after treatment, and the incidence of endpoint events, defined as eGFR increasing by more than 25% above baseline, eGFR >75 mL/min per 1.73 m2 or the composite endpoint, which was defined as the sum of patients meeting either of the above criteria. RESULTS: Data from a total of 114 patients (59 in the YQPY group and 55 in the control group) were analyzed. The mean changes in eGFR and Scr in weeks 4 and 24 had no difference between the two groups. In further subgroup analysis (22 in the YQPY group and 31 in the control group), the mean change in eGFR after treatment for 4 weeks was 27.39 mL/min per 1.73 m2 in the YQPY group and 5.78 mL/min per 1.73 m2 in the placebo group, and the mean difference between groups was 21.61 mL/min per 1.73 m2 (P < 0.001). Thirteen (59.1%) patients in the YQPY group and 5 (16.1%) in the placebo group reached the composite endpoints (P = 0.002). During the intervention, 2 and 4 severe adverse events were reported in the YQPY and placebo groups, respectively. CONCLUSION: The YQPY granules can effectively improve the renal function of patients 4 weeks after the onset of AKI, indicating that it has good efficacy for improving short-term renal outcomes in patients with AKI. The YQPY granules may be a promising therapy for adults with AKI. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100051723. Please cite this article as: Wu JJ, Zhang TY, Qi YH, Zhu MY, Fang Y, Qi CJ, Cao LO, Lu JF, Lu BH, Tang LM, Shen JX, Mou S. Efficacy and safety of Yiqi Peiyuan granules for improving the short-term prognosis of patients with acute kidney injury: a multicenter, double-blind, placebo-controlled, randomized trial. J Integr Med. 2024; 22(3): 279-285.

Bhlhe40 Promotes CD4+ T Helper 1 Cell and Suppresses T Follicular Helper Cell Differentiation during Viral Infection.

In response to acute infection, naive CD4+ T cells primarily differentiate into T helper 1 (Th1) or T follicular helper (Tfh) cells that play critical roles in orchestrating cellular or humoral arms of immunity, respectively. However, despite the well established role of T-bet and BCL-6 in driving Th1 and Tfh cell lineage commitment, respectively, whether additional transcriptional circuits also underlie the fate bifurcation of Th1 and Tfh cell subsets is not fully understood. In this article, we study how the transcriptional regulator Bhlhe40 dictates the Th1/Tfh differentiation axis in mice. CD4+ T cell-specific deletion of Bhlhe40 abrogates Th1 but augments Tfh differentiation. We also assessed an increase in germinal center B cells and Ab production, suggesting that deletion of Bhlhe40 in CD4+ T cells not only alters Tfh differentiation but also their capacity to provide help to B cells. To identify molecular mechanisms by which Bhlhe40 regulates Th1 versus Tfh lineage choice, we first performed epigenetic profiling in the virus specific Th1 and Tfh cells following LCMV infection, which revealed distinct promoter and enhancer activities between the two helper cell lineages. Furthermore, we identified that Bhlhe40 directly binds to cis-regulatory elements of Th1-related genes such as Tbx21 and Cxcr6 to activate their expression while simultaneously binding to regions of Tfh-related genes such as Bcl6 and Cxcr5 to repress their expression. Collectively, our data suggest that Bhlhe40 functions as a transcription activator to promote Th1 cell differentiation and a transcription repressor to suppress Tfh cell differentiation.

Effectiveness of fecal DNA syndecan-2 methylation testing for detection of colorectal cancer in a high-risk Chinese population.

BACKGROUND: Colorectal cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. Syndecan-2 methylation (mSDC2) testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. Cancer (CRC) is among the most prevalent and life-threatening malignancies worldwide. mSDC2 testing has emerged as a widely used biomarker for early detection of CRC in stool and serum samples. AIM: To validate the effectiveness of fecal DNA mSDC2 testing in the detection of CRC among a high-risk Chinese population to provide evidence-based data for the development of diagnostic and/or screening guidelines for CRC in China. METHODS: A high-risk Chinese cohort consisting of 1130 individuals aged 40-79 years was selected for evaluation via fecal mSDC2 testing. Sensitivity and specificity for CRC, advanced adenoma (AA) and advanced colorectal neoplasia (ACN) were determined. High-risk factors for the incidence of colorectal lesions were determined and a logistic regression model was constructed to reflect the efficacy of the test. RESULTS: A total of 1035 high-risk individuals were included in this study according to established criteria. Among them, 16 suffered from CRC (1.55%), 65 from AA (6.28%) and 189 from non-AAs (18.26%); 150 patients were diagnosed with polyps (14.49%). Diagnoses were established based upon colonoscopic and pathological examinations. Sensitivities of the mSDC2 test for CRC and AA were 87.50% and 40.00%, respectively; specificities were 95.61% for other groups. Positive predictive values of the mSDC2 test for CRC, AA and ACN were 16.09%, 29.89% and 45.98%, respectively; the negative predictive value for CRC was 99.79%. After adjusting for other high-risk covariates, mSDC2 test positivity was found to be a significant risk factor for the occurrence of ACN (P < 0.001). CONCLUSION: Our findings confirmed that offering fecal mSDC2 testing and colonoscopy in combination for CRC screening is effective for earlier detection of malignant colorectal lesions in a high-risk Chinese population.

Voxel-Wise Fusion of 3T and 7T Diffusion MRI Data to Extract more Accurate Fiber Orientations.

While 7T diffusion magnetic resonance imaging (dMRI) has high spatial resolution, its diffusion imaging quality is usually affected by signal loss due to B1 inhomogeneity, T2 decay, susceptibility, and chemical shift. In contrast, 3T dMRI has relative higher diffusion angular resolution, but lower spatial resolution. Combination of 3T and 7T dMRI, thus, may provide more detailed and accurate information about the voxel-wise fiber orientations to better understand the structural brain connectivity. However, this topic has not yet been thoroughly explored until now. In this study, we explored the feasibility of fusing 3T and 7T dMRI data to extract voxel-wise quantitative parameters at higher spatial resolution. After 3T and 7T dMRI data was preprocessed, respectively, 3T dMRI volumes were coregistered into 7T dMRI space. Then, 7T dMRI data was harmonized to the coregistered 3T dMRI B0 (b = 0) images. Last, harmonized 7T dMRI data was fused with 3T dMRI data according to four fusion rules proposed in this study. We employed high-quality 3T and 7T dMRI datasets (N = 24) from the Human Connectome Project to test our algorithms. The diffusion tensors (DTs) and orientation distribution functions (ODFs) estimated from the 3T-7T fused dMRI volumes were statistically analyzed. More voxels containing multiple fiber populations were found from the fused dMRI data than from 7T dMRI data set. Moreover, extra fiber directions were extracted in temporal brain regions from the fused dMRI data at Otsu's thresholds of quantitative anisotropy, but could not be extracted from 7T dMRI dataset. This study provides novel algorithms to fuse intra-subject 3T and 7T dMRI data for extracting more detailed information of voxel-wise quantitative parameters, and a new perspective to build more accurate structural brain networks.

Reconstruction of the genome-scale metabolic network model of Sinorhizobium fredii CCBAU45436 for free-living and symbiotic states.

Sinorhizobium fredii CCBAU45436 is an excellent rhizobium that plays an important role in agricultural production. However, there still needs more comprehensive understanding of the metabolic system of S. fredii CCBAU45436, which hinders its application in agriculture. Therefore, based on the first-generation metabolic model iCC541 we developed a new genome-scale metabolic model iAQY970, which contains 970 genes, 1,052 reactions, 942 metabolites and is scored 89% in the MEMOTE test. Cell growth phenotype predicted by iAQY970 is 81.7% consistent with the experimental data. The results of mapping the proteome data under free-living and symbiosis conditions to the model showed that the biomass production rate in the logarithmic phase was faster than that in the stable phase, and the nitrogen fixation efficiency of rhizobia parasitized in cultivated soybean was higher than that in wild-type soybean, which was consistent with the actual situation. In the symbiotic condition, there are 184 genes that would affect growth, of which 94 are essential; In the free-living condition, there are 143 genes that influence growth, of which 78 are essential. Among them, 86 of the 94 essential genes in the symbiotic condition were consistent with the prediction of iCC541, and 44 essential genes were confirmed by literature information; meanwhile, 30 genes were identified by DEG and 33 genes were identified by Geptop. In addition, we extracted four key nitrogen fixation modules from the model and predicted that sulfite reductase (EC 1.8.7.1) and nitrogenase (EC 1.18.6.1) as the target enzymes to enhance nitrogen fixation by MOMA, which provided a potential focus for strain optimization. Through the comprehensive metabolic model, we can better understand the metabolic capabilities of S. fredii CCBAU45436 and make full use of it in the future.