A light-driven enzymatic enantioselective radical acylation.

Enzymes are recognized as exceptional catalysts for achieving high stereoselectivities1-3, but their ability to control the reactivity and stereoinduction of free radicals lags behind that of chemical catalysts4. Thiamine diphosphate (ThDP)-dependent enzymes5 are well-characterized systems that inspired the development of N-heterocyclic carbenes (NHCs)6-8 but have not yet been proved viable in asymmetric radical transformations. There is a lack of a biocompatible and general radical-generation mechanism, as nature prefers to avoid radicals that may be harmful to biological systems9. Here we repurpose a ThDP-dependent lyase as a stereoselective radical acyl transferase (RAT) through protein engineering and combination with organophotoredox catalysis10. Enzyme-bound ThDP-derived ketyl radicals are selectively generated through single-electron oxidation by a photoexcited organic dye and then cross-coupled with prochiral alkyl radicals with high enantioselectivity. Diverse chiral ketones are prepared from aldehydes and redox-active esters (35 examples, up to 97% enantiomeric excess (e.e.)) by this method. Mechanistic studies reveal that this previously elusive dual-enzyme catalysis/photocatalysis directs radicals with the unique ThDP cofactor and evolvable active site. This work not only expands the repertoire of biocatalysis but also provides a unique strategy for controlling radicals with enzymes, complementing existing chemical tools.

AdaPPI: identification of novel protein functional modules via adaptive graph convolution networks in a protein-protein interaction network.

Identifying unknown protein functional modules, such as protein complexes and biological pathways, from protein-protein interaction (PPI) networks, provides biologists with an opportunity to efficiently understand cellular function and organization. Finding complex nonlinear relationships in underlying functional modules may involve a long-chain of PPI and pose great challenges in a PPI network with an unevenly sparse and dense node distribution. To overcome these challenges, we propose AdaPPI, an adaptive convolution graph network in PPI networks to predict protein functional modules. We first suggest an attributed graph node presentation algorithm. It can effectively integrate protein gene ontology attributes and network topology, and adaptively aggregates low- or high-order graph structural information according to the node distribution by considering graph node smoothness. Based on the obtained node representations, core cliques and expansion algorithms are applied to find functional modules in PPI networks. Comprehensive performance evaluations and case studies indicate that the framework significantly outperforms state-of-the-art methods. We also presented potential functional modules based on their confidence.

The Highly Conserved Stem-Loop II Motif Is Dispensable for SARS-CoV-2.

The stem-loop II motif (s2m) is an RNA structural element that is found in the 3' untranslated region (UTR) of many RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Though the motif was discovered over 25 years ago, its functional significance is unknown. In order to understand the importance of s2m, we created viruses with deletions or mutations of the s2m by reverse genetics and also evaluated a clinical isolate harboring a unique s2m deletion. Deletion or mutation of the s2m had no effect on growth in vitro or on growth and viral fitness in Syrian hamsters in vivo. We also compared the secondary structure of the 3' UTR of wild-type and s2m deletion viruses using selective 2'-hydroxyl acylation analyzed by primer extension and mutational profiling (SHAPE-MaP) and dimethyl sulfate mutational profiling and sequencing (DMS-MaPseq). These experiments demonstrate that the s2m forms an independent structure and that its deletion does not alter the overall remaining 3'-UTR RNA structure. Together, these findings suggest that s2m is dispensable for SARS-CoV-2. IMPORTANCE RNA viruses, including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), contain functional structures to support virus replication, translation, and evasion of the host antiviral immune response. The 3' untranslated region of early isolates of SARS-CoV-2 contained a stem-loop II motif (s2m), which is an RNA structural element that is found in many RNA viruses. This motif was discovered over 25 years ago, but its functional significance is unknown. We created SARS-CoV-2 with deletions or mutations of the s2m and determined the effect of these changes on viral growth in tissue culture and in rodent models of infection. Deletion or mutation of the s2m element had no effect on growth in vitro or on growth and viral fitness in Syrian hamsters in vivo. We also observed no impact of the deletion on other known RNA structures in the same region of the genome. These experiments demonstrate that s2m is dispensable for SARS-CoV-2.

Reconfigurable multi-channel microwave photonic receiver for a multi-band signal based on cascaded microring resonator banks.

What we believe to be a novel reconfigurable multi-channel microwave photonic (MWP) receiver for multi-band RF signal is demonstrated for the first time, to the best of our knowledge. A reconfigurable MWP signal processing chip based on two cascaded microring filter banks is employed in the proposed receiver, which slices the multi-band RF input into several narrow band signals and selects optical frequency comb lines for frequency converting of each channel. Due to the significant reconfigurability of the signal processing chip, the proposed receiver can flexibly choose the output frequency band of each channel, and thus different frequency components of the multi-band RF input can be down converted to the intermediate frequency (IF) band for receiving or converted to other frequency band for forwarding. A multi-band RF signal composed of a linear frequency modulation (LFM) signal with 2 GHz bandwidth and a quad-phase shift keyed (QPSK) signal with 100 Mbit/s rate is experimentally received and reconstructed by the proposed receiver, where the reconstructed LFM component exhibits a signal to noise ratio (SNR) of 10.2 dB, and the reconstructed QPSK component reaches a high SNR of 26.1 dB and a great error vector magnitude (EVM) of 11.73%. On the other hand, the QPSK component of the multi-band RF signal centered at 13.5 GHz is successfully converted to 3.1 GHz.

High expression of TBRG4 in relation to unfavorable outcome and cell ferroptosis in hepatocellular carcinoma.

BACKGROUND: Hepatocellular carcinoma (HCC) is the most common type of malignant liver tumor with poor prognosis. In this study, we investigated the expression of transforming growth factor beta regulator 4 (TBRG4) in HCC and its effects on the proliferation, invasion, and metastasis of HCC cells, and analyzed the possible molecular mechanisms. METHOD: Downloading the expression and clinical information of HCC samples in the TCGA database, analyzing the expression differences of TBRG4 by bioinformatics methods, analyzing the clinical relevance and prognostic significance. Performing GO, KEGG and GSEA enrichment analysis on the TBRG4-related gene set in patient HCC tissues. Applying cell counting, scratch test and Transwell experiment to study the biological function of TBRG4 in HCC. Mitochondrial membrane potential, apoptosis and ROS levels were evaluated to assess cell iron death. Western blot, RT-PCR, laser confocal microscopy and co-immunoprecipitation were used to detect and analyze the downstream signaling pathways and interacting molecules of TBRG4. RESULTS: Bioinformatics analysis revealed that TBRG4 was abnormally highly expressed in HCC tumor tissues and was associated with poor prognosis and metastasis in HCC patients. GO and KEGG functional enrichment analysis showed that TBRG4 was related to oxidative stress and NADH dehydrogenase (ubiquinone) activity. GSEA enrichment analysis showed that TBRG4 was associated with Beta catenin independent wnt signaling and B cell receptor. Functional experiments confirmed that knocking down TBRG4 could inhibit the proliferation, migration, and invasion of HCC cells. Mechanistically, TBRG4 inhibited the function of HCC cells through the DDX56/p-AKT/GSK3ß signaling pathway. In addition, interference with TBRG4 expression could reduce the mitochondrial membrane potential and accumulate ROS in HCC cells, leading to increased ferroptosis. Co-IP analysis showed that TBRG4 specifically bound to Beclin1. CONCLUSION: TBRG4 is highly expressed in HCC tumor tissues and is associated with poor prognosis. It may regulate the proliferation, invasion, and metastasis of HCC cells through the DDX56/p-AKT/GSK3ß signaling pathway. TBRG4 may interact with Beclin1 to regulate the ferroptosis of HCC cells.

UHPLC-HRMS-based Multiomics to Explore the Potential Mechanisms and Biomarkers for Colorectal Cancer.

BACKGROUND: Understanding the metabolic changes in colorectal cancer (CRC) and exploring potential diagnostic biomarkers is crucial for elucidating its pathogenesis and reducing mortality. Cancer cells are typically derived from cancer tissues and can be easily obtained and cultured. Systematic studies on CRC cells at different stages are still lacking. Additionally, there is a need to validate our previous findings from human serum. METHODS: Ultrahigh-performance liquid chromatography tandem high-resolution mass spectrometry (UHPLC-HRMS)-based metabolomics and lipidomics were employed to comprehensively measure metabolites and lipids in CRC cells at four different stages and serum samples from normal control (NR) and CRC subjects. Univariate and multivariate statistical analyses were applied to select the differential metabolites and lipids between groups. Biomarkers with good diagnostic efficacy for CRC that existed in both cells and serum were screened by the receiver operating characteristic curve (ROC) analysis. Furthermore, potential biomarkers were validated using metabolite standards. RESULTS: Metabolite and lipid profiles differed significantly among CRC cells at stages A, B, C, and D. Dysregulation of glycerophospholipid (GPL), fatty acid (FA), and amino acid (AA) metabolism played a crucial role in the CRC progression, particularly GPL metabolism dominated by phosphatidylcholine (PC). A total of 46 differential metabolites and 29 differential lipids common to the four stages of CRC cells were discovered. Eight metabolites showed the same trends in CRC cells and serum from CRC patients compared to the control groups. Among them, palmitoylcarnitine and sphingosine could serve as potential biomarkers with the values of area under the curve (AUC) more than 0.80 in the serum and cells. Their panel exhibited excellent performance in discriminating CRC cells at different stages from normal cells (AUC = 1.00). CONCLUSIONS: To our knowledge, this is the first research to attempt to validate the results of metabolism studies of serum from CRC patients using cell models. The metabolic disorders of PC, FA, and AA were closely related to the tumorigenesis of CRC, with PC being the more critical factor. The panel composed of palmitoylcarnitine and sphingosine may act as a potential biomarker for the diagnosis of CRC, aiding in its prevention.

Effect of baicalin on eradicating biofilms of bovine milk derived Acinetobacter lwoffii.

BACKGROUND: Acinetobacter lwoffii (A.lwoffii) is a serious zoonotic pathogen that has been identified as a cause of infections such as meningitis, bacteremia and pneumonia. In recent years, the infection rate and detection rate of A.lwoffii is increasing, especially in the breeding industry. Due to the presence of biofilms, it is difficult to eradicate and has become a potential super drug-resistant bacteria. Therefore, eradication of preformed biofilm is an alternative therapeutic action to control A.lwoffii infection. The present study aimed to clarify that baicalin could eradicate A.lwoffii biofilm in dairy cows, and to explore the mechanism of baicalin eradicating A.lwoffii. RESULTS: The results showed that compared to the control group, the 4 MIC of baicalin significantly eradicated the preformed biofilm, and the effect was stable at this concentration, the number of viable bacteria in the biofilm was decreased by 0.67 Log10CFU/mL. The total fluorescence intensity of biofilm bacteria decreased significantly, with a reduction rate of 67.0%. There were 833 differentially expressed genes (367 up-regulated and 466 down-regulated), whose functions mainly focused on oxidative phosphorylation, biofilm regulation system and trehalose synthesis. Molecular docking analysis predicted 11 groups of target proteins that were well combined with baicalin, and the content of trehalose decreased significantly after the biofilm of A.lwoffii was treated with baicalin. CONCLUSIONS: The present study evaluated the antibiofilm potential of baicalin against A.lwoffii. Baicalin revealed strong antibiofilm potential against A.lwoffii. Baicalin induced biofilm eradication may be related to oxidative phosphorylation and TCSs. Moreover, the decrease of trehalose content may be related to biofilm eradication.

The body mass index and the risk of ectopic pregnancy: a 5-year retrospective case-control study.

PURPOSE: Acknowledging the associated risk factors may have a positive impact on reducing the incidence of ectopic pregnancy (EP). In recent years, body mass index (BMI) has been mentioned in research. However, few studies are available and controversial on the relationship between EP and BMI. METHODS: We retrospectively studied the EP women as a case group and the deliveries as a control group in the central hospital of Wuhan during 2017 ~ 2021. χ2 test of variables associated with ectopic pregnancy was performed to find differences. Univariate and multivariate binary logistic regression analysis was conducted to analyze the association of the variables of age, parity, history of induced abortion, history of ectopic pregnancy, history of spontaneous abortion, history of appendectomy surgery and BMI (< 18.5 kg/m2, 18.5 ~ 24.9 kg/m2, 25 kg/m2 ~ 29.9 kg/m2, ≥ 30 kg /m2) with EP. RESULTS: They were 659 EP and 1460 deliveries. The variables of age, parity, history of induced abortion, history of ectopic pregnancy and BMI were different significantly(P < 0.05). Multivariate analysis showed that the variables of age > 35 years old [(OR (Odds Ratio), 5.415; 95%CI (Confidence Interval), 4.006 ~ 7.320, P < 0.001], history of ectopic pregnancy (OR, 3.944; 95%CI, 2.405 ~ 6.467; P < 0.001), history of induced abortion(OR, 3.365; 95%CI, 2.724 ~ 4.158, P < 0.001) and low BMI (< 18.5 kg/m2) (OR, 1.929; 95%CI, 1.416 ~ 2.628, P < 0.001])increased the risk of EP. CONCLUSION: The history of ectopic pregnancy, history of induced abortion and age > 35 years old were the risk factors with EP. In addition to these traditional factors, we found low BMI (< 18.5 kg/m2) with women may increase the risk to EP.

Evaluation of the Optimal Duration of Thumb Cupping Therapy for Frozen Shoulder by Thermal Metabolic Imaging.

Objective: To evaluate the optimal duration of thumb cupping therapy for frozen shoulder (FS) by thermal metabolic imaging (TMI) and to provide clinical evidence. Methods: From April 2022 to August 2023, 120 patients with FS who received thumb cupping therapy at our hospital were randomized into groups A, B, and C for 5, 10, and 15 minutes of cupping, respectively. The clinical efficacy, Visual Analogue Scale (VAS) score, and shoulder range of motion (ROM) of the three groups were compared, and the skin blood flow and the incidence of adverse reactions during treatment were analyzed. Finally, the temperature difference improvement efficiency (i.e., higher TMI after treatment than before treatment) was compared among the three groups. Results: Groups B and C showed higher overall clinical efficacy than group A (P < .05). After treatment, lower VAS scores were determined in groups B and C compared with group A, whereas the ROM values of groups A and C were smaller than those of group B Group C had the greatest skin blood flow and the highest incidence of adverse reactions (P < .05), while group B had the highest temperature difference improvement efficiency (P < .05). Conclusions: Through TMI, it is confirmed that thumb cupping therapy with a duration of 10 min contributes to the highest efficacy and safety for patients with FS.

Using MXene as a Chemically Induced Initiator to Construct High-Performance Cathodes for Aqueous Zinc-Ion Batteries.

MXene usually exhibits weak pseudo-capacitance behavior in aqueous zinc-ion batteries, which cannot provide sufficient reversible capacity, resulting in the decline of overall capacity when used as the cathode materials. Taking inspiration from polymer electrolyte engineering, we have conceptualized an in-situ induced growth strategy based on MXene materials. Herein, 5.25 % MXene was introduced into the nucleation and growth process of vanadium oxide (HVO), providing the heterogeneous nucleation site and serving as an initiator to regulate the morphology and structural of vanadium oxide (T-HVO). The resulted materials can significantly improve the capacity and rate performance of zinc-ion batteries. The growth mechanism of T-HVO was demonstrated by both characterizations and DFT simulations, and the improved performance was systematically investigated through a series of in-situ experiments related to dynamic analysis steps. Finally, the evaluation and comparison of various defect introduction strategies revealed the efficient, safety, and high production output characteristics of the in-situ induced growth strategy. This work proposes the concept of in-situ induced growth strategy and discloses the induced chemical mechanism of MXene materials, which will aid the understanding, development, and application of cathode in aqueous zinc-ion batteries.

Immobilization of the Polar Group into an Ultramicroporous Metal-Organic Framework Enabling Benchmark Inverse Selective CO2/C2H2 Separation with Record C2H2 Production.

One-step harvest of high-purity light hydrocarbons without the desorption process represents an advanced and highly efficient strategy for the purification of target substances. The separation and purification of acetylene (C2H2) from carbon dioxide (CO2) by CO2-selective adsorbents are urgently demanded yet are very challenging owing to their similar physicochemical properties. Here, we employ the pore chemistry strategy to adjust the pore environment by immobilizing polar groups into an ultramicroporous metal-organic framework (MOF), achieving one-step manufacture of high-purity C2H2 from CO2/C2H2 mixtures. Embedding methyl groups into prototype stable MOF (Zn-ox-trz) not only changes the pore environment but also improves the discrimination of guest molecules. The methyl-functionalized Zn-ox-mtz thus exhibits the benchmark reverse CO2/C2H2 uptake ratio of 12.6 (123.32/9.79 cm3 cm-3) and an exceptionally high equimolar CO2/C2H2 selectivity of 1064.9 at ambient conditions. Molecular simulations reveal that the synergetic effect of pore confinement and surfaces decorated with methyl groups provides high recognition of CO2 molecules through multiple van der Waals interactions. The column breakthrough experiments suggest that Zn-ox-mtz dramatically achieved the one-step purification capacity of C2H2 from the CO2/C2H2 mixture with a record C2H2 productivity of 2091 mmol kg-1, surpassing all of the CO2-selective adsorbents reported so far. In addition, Zn-ox-mtz exhibits excellent chemical stability under different pH values of aqueous solutions (pH = 1-12). Moreover, the highly stable framework and excellent inverse selective CO2/C2H2 separation performance showcase its promising application as a C2H2 splitter for industrial manufacture. This work paves the way to developing reverse-selective adsorbents for the challenging gas separation process.

Pocket-Size Wireless Nanoelectrospray Ionization Mass Spectrometry for Metabolic Analysis of Salty Biofluids and Single Cells.

Analysis of volume-limited biological samples such as single cells and biofluids not only benefits clinical purposes but also promotes fundamental research in life sciences. Detection of these samples, however, imposes strict requirements on measurement performance because of the minimal volume and concentrated salts of the samples. Herein, we developed a self-cleaning nanoelectrospray ionization device powered by a pocket-size "MasSpec Pointer" (MSP-nanoESI) for metabolic analysis of salty biological samples with limited volume. The self-cleaning effect induced by Maxwell-Wagner electric stress helps with keeping the borosilicate glass capillary tip free from clogging and thus increasing salt tolerance. This device possesses a high sample economy (about 0.1 µL per test) due to its pulsed high voltage supply, sampling method (dipping the nanoESI tip into analyte solution), and contact-free electrospray ionization (ESI) (the electrode does not touch the analyte solution during ESI). High repeatable results could be acquired by the device with a relative standard deviation (RSD) of 1.02% for voltage output and 12.94% for MS signals of caffeine standard. Single MCF-7 cells were metabolically analyzed directly from phosphate buffered saline, and two types of untreated cerebrospinal fluid from hydrocephalus patients were distinguished with 84% accuracy. MSP-nanoESI gets rid of the bulky apparatus and could be held in hand or put into one's pocket for transportation, and it could operate for more than 4 h without recharge. We believe this device will boost scientific research and clinical usage of volume-limited biological samples with high-concentration salts in a low-cost, convenient, and rapid manner.

Mesenchymal stem cells inhibit MRP-8/14 expression and neutrophil migration via TSG-6 in the treatment of lupus nephritis.

Abnormal infiltration and activation of neutrophils play a pathogenic role in the development of lupus nephritis (LN). Myeloid-related proteins (MRPs), MRP-8 and -14, also known as the damage-associated molecular patterns (DAMPs), are mainly secreted by activated neutrophils in systemic lupus erythematosus (SLE). Mesenchymal stem cells (MSCs) regulate a variety of immune cells to treat LN, but it is not clear whether MSCs can regulate neutrophils and the expression of MRP-8/14 in LN. Here, we demonstrated that neutrophil infiltration and MRP-8/14 expression were increased in the kidney of MRL/lpr mice and both decreased after MSCs transplantation. Further, the results showed that tumor necrosis factor- (TNF) stimulated gene-6 (TSG-6) in MSCs is necessary for MSCs to inhibit MRP-8/14 expression in neutrophils and neutrophil migration. In addition, small-molecule immunosuppressant had no significant effect on the expression of MRP-8/14 in neutrophils. Therefore, our results suggest that MSCs inhibited MRP-8/14 expression and neutrophil migration by secreting TSG-6 in the treatment of LN.

A natural variation in the promoter of GRA117 affects carbon assimilation in rice.

MAIN CONCLUSION: GRA117 is crucial in the process of carbon assimilation in rice as it regulates the development of chloroplasts, which in turn facilitates the Calvin-Benson cycle. Carbon assimilation is a critical process for plant growth, and despite numerous relevant studies, there are still unknown constraints. In this study, we isolated a rice mutant, gra117, which exhibited seedling albinism, delayed chloroplast development, decreased chlorophyll content, reduced yield, and seedling stress susceptibility, as compared to WT. Our further investigations revealed that gra117 had a significantly lower net photosynthetic carbon assimilation rate, as well as reduced levels of Rubisco enzyme activity, RUBP, PGA, carbohydrate, protein content, and dry matter accumulation. These findings provide evidence for decreased carbon assimilation in gra117. By mapping cloning, we discovered a 665 bp insertion in the GRA117 promoter region that decreases GRA117 transcriptional activity and causes the gra117 phenotype. GRA117 encodes PfkB-type fructokinase-like 2, which is subcellularly localized in chloroplasts and is widely expressed in various rice tissues, particularly at high levels in leaf tissues. GRA117 transcription is regulated by the core region 1029 bp before the start codon. Our quantitative RT-PCR and Western blot assays showed that GRA117 promotes the expression and translation of photosynthetic genes. RNA-Seq analysis revealed that GRA117 plays a significant role in photosynthetic carbon fixation, carbon metabolism, and chloroplast ribosome-related pathways. Our study supports that GRA117 promotes the Calvin-Benson cycle by regulating chloroplast development, ultimately leading to enhanced carbon assimilation in rice.

Cucurbitacin E reduces IL-1ß-induced inflammation and cartilage degeneration by inhibiting the PI3K/Akt pathway in osteoarthritic chondrocytes.

BACKGROUND: Osteoarthritis is a degenerative joint disease. Cartilage degeneration is the earliest and most important pathological change in osteoarthritis, and persistent inflammation is one of the driving factors of cartilage degeneration. Cucurbitacin E, an isolated compound in the Cucurbitacin family, has been shown to have anti-inflammatory effects, but its role and mechanism in osteoarthritic chondrocytes are unclear. METHODS: For in vitro experiments, human chondrocytes were stimulated with IL-1ß, and the expression of inflammatory genes was measured by Western blotting and qPCR. The expression of extracellular matrix proteins was evaluated by immunofluorescence staining, Western blotting and saffron staining. Differences in gene expression between cartilage from osteoarthritis patients and normal cartilage were analysed by bioinformatics methods, and the relationship between Cucurbitacin E and its target was analysed by a cellular thermal shift assay, molecular docking analysis and molecular dynamics simulation. For in vivo experiments, knee osteoarthritis was induced by DMM in C57BL/6 mouse knee joints, and the effect of Cucurbitacin E on knee joint degeneration was evaluated. RESULTS: The in vitro experiments confirmed that Cucurbitacin E effectively inhibited the production of the inflammatory cytokine interleukin-1ß(IL-1ß) and cyclooxygenase-2 (COX-2) by IL-1ß-stimulated chondrocytes and alleviates extracellular matrix degradation. The in vivo experiments demonstrated that Cucurbitacin E had a protective effect on the knee cartilage of C57BL/6 mice with medial meniscal instability in the osteoarthritis model. Mechanistically, bioinformatic analysis of the GSE114007 and GSE117999 datasets showed that the PI3K/AKT pathway was highly activated in osteoarthritis. Immunohistochemical analysis of PI3K/Akt signalling pathway proteins in pathological slices of human cartilage showed that the level of p-PI3K in patients with osteoarthritis was higher than that in the normal group. PI3K/Akt were upregulated in IL-1ß-stimulated chondrocytes, and Cucurbitacin E intervention reversed this phenomenon. The cellular thermal shift assay, molecular docking analysis and molecular dynamics experiment showed that Cucurbitacin E had a strong binding affinity for the inhibitory target PI3K. SC79 activated Akt phosphorylation and reversed the effect of Cucurbitacin E on IL-1ß-induced chondrocyte degeneration, demonstrating that Cucurbitacin E inhibits IL-1ß-induced chondrocyte inflammation and degeneration by inhibiting the PI3K/AKT pathway. CONCLUSION: Cucurbitacin E inhibits the activation of the PI3K/AKT pathway, thereby alleviating the progression of OA. In summary, we believe that Cucurbitacin E is a potential drug for the treatment of OA.

Microbiota profiles in the saliva, cancerous tissues and its companion paracancerous tissues among Chinese patients with lung cancer.

BACKGROUND: Despite the growing interest in the impact of the gut microbiome on cancer, the relationship between the lung microbiome and lung cancer has received limited investigation. Additionally, the composition of the oral microbiome was found to differ from that of individuals with lung cancer, indicating that these microorganisms may serve as potential biomarkers for the detection of lung cancer. METHODS: Forty-three Chinese lung cancer patients were enrolled in the current retrospective study and 16 S rRNA sequencing was performed on saliva, cancerous tissue (CT) and paracancerous tissue (PT) samples. RESULTS: Diversity and species richness were significantly different between the oral and lung microbiota. Lung microbiota were largely composed of the phyla Proteobacteria, Firmicutes, Bacteroidetes and Actinobacteria. The relative abundance of Promicromonosporacea and Chloroflexi increased in CT, while Enterococcaceae and Enterococcus were enriched in PT (p<0.05). A cancer-related microbiota model was constructed and produced an area under the curve of 0.74 in the training set, indicating discrimination between subjects with and without cancer. CONCLUSIONS: Characterization of microbiota in saliva, CT and PT from Chinese lung cancer patients revealed little difference between CT and PT, indicating that the tumor and its microenvironment might influence the local microbiome. A model to distinguish between CT and PT was constructed, which has the potential to enhance our comprehension of the involvement of microbiota in the pathogenesis of lung cancer and identify novel therapeutic targets.

Symptom profiles and vaccination status for COVID-19 after the adjustment of the dynamic zero-COVID policy in China: An observational study.

There has been a substantial rise in coronavirus disease 2019 (COVID-19) cases after adjusting the dynamic zero-COVID policy in China. We conducted a survey to investigate the self-perceived symptom profile and its association with vaccination status during this outbreak. There were 552 individuals in this survey. The infected individuals displayed various symptoms associated with different factors. The three most common symptoms were fatigue (92.21%), phlegm (91.49%), and cough (89.31%). Two typical clusters of COVID-19 symptoms were identified through hierarchical clustering: one was the symptoms with a high probability of co-occurrence that primarily involved the upper respiratory tract, and the other was the symptoms with a high prevalence of severe cases that affected multiple systems. Symptoms exhibited distinct across regions. Hebei Province reported the most severe respiratory symptoms, and Chongqing City reported the worst neurological and digestive symptoms. Cough and fatigue occurred together in most regions. Nevertheless, the cough severity of Zhejiang, Liaoning, and Yunnan provinces was lower than in other areas (t-test p < 0.001). Regression analysis suggested a potential protective effect of recent vaccination on some symptoms. Compared with people who had been vaccinated within half a year, those for more than 1 year had a higher risk of developing phlegm, cough, vertigo, and nausea (all p < 0.05). Our study illustrated the characteristics and symptom profiles of COVID-19 during this wave and provided data supporting its relationship with multiple factors. These findings offered new insights into the recent COVID-19 pandemic in China.

Mendelian randomization suggests a potential causal effect of eosinophil count on influenza vaccination responsiveness.

Currently, the clinical factors affecting immune responses to influenza vaccines have not been systematically explored. The mechanism of low responsiveness to influenza vaccination (LRIV) is complicated and not thoroughly elucidated. Thus, we integrate our in-house genome-wide association studies (GWAS) analysis result of LRIV (N = 111, Ncase [Low Responders] = 34, Ncontrol [Responders] = 77) with the GWAS summary of 10 blood-based biomarkers (sample size ranging from 62 076-108 794) deposited in BioBank Japan (BBJ) to comprehensively explore the shared genetics between LRIV and blood-based biomarkers to investigate the causal relationships between blood-based biomarkers and LRIV by Mendelian randomization (MR). The applications of four MR approaches (inverse-variance-weighted [IVW], weighted median, weighted mode, and generalized summary-data-based MR [GSMR]) suggested that the genetically instrumented LRIV was associated with decreased eosinophil count (ß = -5.517 to -4.422, p = 0.004-0.039). Finally, we conclude that the low level of eosinophil count is a suggestive risk factor for LRIV.

C-DONN: compact diffractive optical neural network with deep learning regression.

A new method to improve the integration level of an on-chip diffractive optical neural network (DONN) is proposed based on a standard silicon-on-insulator (SOI) platform. The metaline, which represents a hidden layer in the integrated on-chip DONN, is composed of subwavelength silica slots, providing a large computation capacity. However, the physical propagation process of light in the subwavelength metalinses generally requires an approximate characterization using slot groups and extra length between adjacent layers, which limits further improvements of the integration of on-chip DONN. In this work, a deep mapping regression model (DMRM) is proposed to characterize the process of light propagation in the metalines. This method improves the integration level of on-chip DONN to over 60,000 and elimnates the need for approximate conditions. Based on this theory, a compact-DONN (C-DONN) is exploited and benchmarked on the Iris plants dataset to verify the performance, yielding a testing accuracy of 93.3%. This method provides a potential solution for future large-scale on-chip integration.

WSL214 negatively regulates ROS accumulation and pathogen defense response in rice.

KEY MESSAGE: WSL214 plays an important role in promoting cellular ROS homeostasis by enhancing catalase activity and reducing photosynthetic ROS production. ROS are the important regulator of cellular homeostasis, and balancing ROS production and clearance contributes to cellular activity. Although many genes associated with ROS have been cloned, the mechanism of this balance is not fully understood. In this study, we obtained the rice mutant wsl214 that arose from a natural mutation. Compared to WT, wsl214 exhibited white-striped leaves, defective chloroplast development, reduced net photosynthetic rate, and overexcitation of photosynthetically active reaction centers. In addition, the ROS accumulation level was significantly elevated, and the ROS scavenging enzyme activity was significantly decreased in wsl214 leaf tissue. As a result of elevated ROS levels, wsl214 leaf cells underwent DNA damage and programmed cell death. However, wsl214 defense response to exogenous pathogens was also enhanced by high ROS levels. Based on the mapping cloning, we discovered that WSL214 had a single base mutation (C to T) in the third exon, resulting in decreased expression of wsl214. The WSL214 encodes an HD domain phosphohydrolase and is widely expressed in various tissues of rice, especially at the highest level in leaf tissue. Further research showed that WSL214 promoted the homeostasis of rice leaf cellular ROS in two ways. First, WSL214 increased the expression of the catalase gene OsCATC, making the intracellular ROS scavenging enzyme more active. Second, WSL214 promoted chloroplast development, kept photosynthesis working properly, and reduced ROS produced by photosynthesis. In conclusion, our report emphasizes that WSL214 is a key part of balancing ROS levels in cells.