The levels of soluble CD137 are increased in tuberculosis patients and associated with disease severity and prognosis.

Tuberculosis (TB) was the leading cause of death from a single infectious agent before the coronavirus pandemic. Therefore, it is important to search for severity biomarkers and devise appropriate therapies. A total of 139 pulmonary TB (PTB) patients and 80 healthy controls (HCs) were recruited for plasma soluble CD137 (sCD137) detection through ELISA. Moreover, pleural effusion sCD137 levels were measured in 85 TB patients and 36 untreated lung cancer patients. The plasma cytokine levels in 64 patients with PTB and blood immune cell subpopulations in 68 patients with PTB were analysed via flow cytometry. Blood sCD137 levels were higher in PTB patients (p = 0.012) and correlated with disease severity (p = 0.0056). The level of sCD137 in tuberculous pleurisy effusion (TPE) was markedly higher than that in malignant pleurisy effusion (p = 0.018). Several blood cytokines, such as IL-6 (p = 0.0147), IL-8 (p = 0.0477), IP-10 (p ≤ 0.0001) and MCP-1 (p = 0.0057), and some laboratory indices were significantly elevated in severe PTB (SE) patients, but the percentages of total lymphocytes (p = 0.002) and cytotoxic T cells (p = 0.036) were significantly lower in SE patients than in non-SE patients. In addition, the sCD137 level was negatively correlated with the percentage of total lymphocytes (p = 0.0008) and cytotoxic T cells (p = 0.0021), and PTB patients with higher plasma sCD137 levels had significantly shorter survival times (p = 0.0041). An increase in sCD137 is a potential biomarker for severe TB and indicates a poor prognosis.

Association of novel DNAH11 variants with asthenoteratozoospermia lead to male infertility.

BACKGROUND: Bi-allelic variants in DNAH11 have been identified as causative factors in Primary Ciliary Dyskinesia, leading to abnormal respiratory cilia. Nonetheless, the specific impact of these variants on human sperm flagellar and their involvement in male infertility remain largely unknown. METHODS: A collaborative effort involving two Chinese reproductive centers conducted a study with 975 unrelated infertile men. Whole-exome sequencing was employed for variant screening, and Sanger sequencing confirmed the identified variants. Morphological and ultrastructural analyses of sperm were conducted using Scanning Electron Microscopy and Transmission Electron Microscopy. Western Blot Analysis and Immunofluorescence Analysis were utilized to assess protein levels and localization. ICSI was performed to evaluate its efficacy in achieving favorable pregnancy outcomes for individuals with DNAH11 variants. RESULTS: In this study, we identified seven novel variants in the DNAH11 gene in four asthenoteratozoospermia subjects. These variants led the absence of DNAH11 proteins and ultrastructure defects in sperm flagella, particularly affecting the outer dynein arms (ODAs) and adjacent structures. The levels of ODA protein DNAI2 and axoneme related proteins were down regulated, instead of inner dynein arms (IDA) proteins DNAH1 and DNAH6. Two out of four individuals with DNAH11 variants achieved clinical pregnancies through ICSI. The findings confirm the association between male infertility and bi-allelic deleterious variants in DNAH11, resulting in the aberrant assembly of sperm flagella and contributing to asthenoteratozoospermia. Importantly, ICSI emerges as an effective intervention for overcoming reproductive challenges caused by DNAH11 gene variants.

Application of LAMP coupled with NALF for precise detection of mycoplasma pneumoniae.

Mycoplasma pneumoniae (MP),as the most commonly infected respiratory pathogen in community-acquired pneumonia in preschool children,has becoming a prominent factor affecting children's respiratory health.Currently, there is a lack of easy, rapid, and accurate laboratory testing program for MP infection, which causes comparatively difficulty for clinical diagnostic.Here,we utilize loop-mediated isothermal amplification (LAMP) to amplify and characterize the P1 gene of MP, combined with nucleic acid lateral flow (NALF) for fast and visuallized detection of MP.Furthermore, we evaluated and analyzed the sensitivity, specificity and methodological consistency of the method.The results showed that the limit of detection(LoD) of MP-LAMP-NALF assay was down to 100 copys per reaction and there was no cross-reactivity with other pathogens infected the respiratory system. The concordance rate between MP-LAMP-NALF assay with quantitative real-time PCR was 94.3 %,which exhibiting excellent testing performance.We make superior the turnaround time of the MP-LAMP-NALF assay, which takes only about 50 min. In addition, there is no need for precision instruments and no restriction on the laboratory site.Collectively, LAMP-NALF assay targeting the P1 gene for Mycoplasma pneumoniae detection was a easy, precise and visual test which could be widely applied in outpatient and emergency departments or primary hospitals.When further optimized, it could be used as "point-of-care testing" of pathogens or multiple testing for pathogens.

Visible-Light-Induced Multi-Component Nitrooxylation Reactions of α-Diazoesters, Cyclic Ethers, and Tert-Butyl Nitrite Leading to Organic Nitrate Esters.

A simple and efficient strategy has been developed for the synthesis of organic nitrate esters via visible-light-induced multi-component nitrooxylation reactions of α-diazoesters, cyclic ethers, and tert-butyl nitrite under open air atmosphere. This transformation could be conducted under mild and metal-free conditions to provide a number of organic nitrate esters in moderate to good yields using air as the green oxidant.

FoxG1 as a Potential Therapeutic Target for Alzheimer's Disease: Modulating NLRP3 Inflammasome via AMPK/mTOR Autophagy Pathway.

An increasing body of research suggests that promoting microglial autophagy hinders the neuroinflammation initiated though the NLRP3 inflammasome activation in Alzheimer's disease (AD). The function of FoxG1, a crucial transcription factor involved in cell survival by regulating mitochondrial function, remains unknown during the AD process and neuroinflammation occurs. In the present study, we firstly found that Aß peptides induced AD-like neuroinflammation upregulation and downregulated the level of autophagy. Following low-dose Aß25-35 stimulation, FoxG1 expression and autophagy exhibited a gradual increase. Nevertheless, with high-concentration Aß25-35 treatment, progressive decrease in FoxG1 expression and autophagy levels as the concentration of Aß25-35 escalated. In addition, FoxG1 has a positive effect on cell viability and autophagy in the nervous system. In parallel with the Aß25-35 stimulation, we employed siRNA to decrease the expression of FoxG1 in N2A cells. A substantial reduction in autophagy level (Beclin1, LC3II, SQSTM1/P62) and a notable growth in inflammatory response (NLRP3, TNF-α, and IL-6) were observed. In addition, we found FoxG1 overexpression owned the effect on the activation of AMPK/mTOR autophagy pathway and siRNA-FoxG1 successfully abolished this effect. Lastly, FoxG1 suppressed the NLRP3 inflammasome and enhanced the cognitive function in AD-like mouse model induced by Aß25-35. Confirmed by cellular and animal experiments, FoxG1 suppressed NLRP3-mediated neuroinflammation, which was strongly linked to autophagy regulated by AMPK/mTOR. Taken together, FoxG1 may be a critical node in the pathologic progression of AD and has the potential to serve as therapeutic target.

The Clinical Value of Apparent Diffusion Coefficient of Readout Segmentation of Long Variable Echo Trains and Correlation With Ki-67 Expression in Distal Rectal Cancer.

OBJECTIVE: The aim of the study is to explore the clinical value of the apparent diffusion coefficient (ADC) derived from the readout segmentation of long variable echo trains (RESOLVE) technique for identifying clinicopathologic features of distal rectal cancer and correlations between ADC and Ki-67 expression. METHODS: The data of 112 patients with a proven pathology of distal rectal cancer who underwent preoperative magnetic resonance imaging were retrospectively analyzed. The mean ADC value was measured using the "full-layer and center" method. Differences in ADC values and Ki-67 expression in different clinical stages, pathological types, and tumor differentiation were compared using analysis of variance. Correlations between ADC value and clinicopathologic features were assessed using Spearman correlation analysis. RESULTS: Interobserver agreement of confidence levels from 2 radiologists was excellent for ADC measurement ( k =  0.85). Patients with a lower clinical stage, well-differentiated adenocarcinomas, and a higher possibility of mucinous adenocarcinoma exhibited a positive correlation with higher ADC values, but these factors were negatively correlated with Ki-67 expression (all P < 0.05). We found that ADC value was negatively correlated with Ki-67 expression ( r = -0.62, P < 0.001). CONCLUSIONS: The ADC value generated by RESOLVE sequences was significantly associated with clinicopathologic features and Ki-67 expression in patients with distal rectal cancer in this study. Thus, the ADC value could be considered a new noninvasive imaging biomarker that could be helpful in predicting the biological properties of distal rectal cancer.

Achieving an optimal pregnancy outcome through the combined utilization of micro-TESE and ICSI in cryptorchidism associated with a non-canonical splicing variant in RXFP2.

PURPOSE: To identify the genetic cause of a cryptorchidism patient carrying a non-canonical splicing variant highlighted by SPCards platform in RXFP2 and to provide a comprehensive overview of RXFP2 variants with cryptorchidism correlation. METHODS: We identified a homozygous non-canonical splicing variant by whole-exome sequencing and Sanger sequencing in a case with cryptorchidism and non-obstructive azoospermia (NOA). As the pathogenicity of this non-canonical splicing variant remained unclear, we initially utilized the SPCards platform to predict its pathogenicity. Subsequently, we employed a minigene splicing assay to further evaluate the influence of the identified splicing variant. Microdissection testicular sperm extraction (micro-TESE) combined with intracytoplasmic sperm injection (ICSI) was performed. PubMed and Human Genome Variant Database (HGMD) were queried to search for RXFP2 variants. RESULTS: We identified a homozygous non-canonical splicing variant (NM_130806: c.1376-12A > G) in RXFP2, and confirmed this variant caused aberrant splicing of exons 15 and 16 of the RXFP2 gene: 11 bases were added in front of exon 16, leading to an abnormal transcript initiation and a frameshift. Fortunately, the patient successfully obtained his biological offspring through micro-TESE combined with ICSI. Four cryptorchidism-associated variants in RXFP2 from 90 patients with cryptorchidism were identified through a literature search in PubMed and HGMD, with different inheritance patterns. CONCLUSION: This is the first cryptorchidism case carrying a novel causative non-canonical splicing RXFP2 variant. The combined approach of micro-TESE and ICSI contributed to an optimal pregnancy outcome. Our literature review demonstrated that RXFP2 variants caused cryptorchidism in a recessive inheritance pattern, rather than a dominant pattern.

Sphingomonas bacteria could serve as an early bioindicator for the development of chlorantraniliprole resistance in Spodoptera frugiperda.

The fall armyworm (Spodoptera frugiperda) was found to have invaded China in December 2018, and in just one year, crops in 26 provinces were heavily affected. Currently, the most effective method for emergency control of fulminant pests is to use of chemical pesticides. Recently, most fall armyworm populations in China were begining to exhibite low level resistance to chlorantraniliprole. At present, it is not possible to sensitively reflect the low level resistance of S. frugiperda by detecting target mutation and detoxification enzyme activity. In this study we found that 12 successive generations of screening with chlorantraniliprole caused S. frugiperda to develop low level resistance to this insecticide, and this phenotype was not attribute to genetic mutations in S. frugiperda, but rather to a marked increase in the relative amount of the symbiotic bacteria Sphingomonas. Using FISH and qPCR assays, we determined the amount of Sphingomonas in the gut of S. frugiperda and found Sphingomonas accumulation to be highest in the 3rd-instar larvae. Additionally, Sphingomonas was observed to provide a protective effect to against chlorantraniliprole stress to S. frugiperda. With the increase of the resistance to chlorantraniliprole, the abundance of bacteria also increased, we propose Sphingomonas monitoring could be adapted into an early warning index for the development of chlorantraniliprole resistance in S. frugiperda populations, such that timely measures can be taken to delay or prevent the widespread propagation of resistance to this highly useful agricultural chemical in S. frugiperda field populations.

Cu-Doped Iron Oxide for the Efficient Electrocatalytic Nitrate Reduction Reaction.

The electrochemical nitrate reduction reaction (NO3RR) is a promising alternative synthetic route for sustainable ammonia (NH3) production, because it not only eliminates nitrate (NO3-) from water but also produces NH3 under mild operating conditions. However, owing to the complicated eight-electron reaction and the competition from the hydrogen evolution reaction, developing catalysts with high activities and Faradaic efficiencies (FEs) is highly imperative to improve the reaction performance. In this study, Cu-doped Fe3O4 flakes are fabricated and demonstrated to be excellent catalysts for electrochemical conversion of NO3- to NH3, with a maximum FE of ∼100% and an NH3 yield of 179.55 ± 16.37 mg h-1 mgcat-1 at -0.6 V vs RHE. Theoretical calculations reveal that doping the catalyst surface with Cu results in a more thermodynamically facile reaction. These results highlight the feasibility of promoting the NO3RR activity using heteroatom doping strategies.

Antibiotic Alternatives: Multifunctional Ultra-Small Metal Nanoclusters for Bacterial Infectious Therapy Application.

The prevalence of major bacterial infections has emerged as a significant menace to human health and life. Conventional treatment methods primarily rely on antibiotic therapy, but the overuse of these drugs has led to a decline in their efficacy. Moreover, bacteria have developed resistance towards antibiotics, giving rise to the emergence of superbugs. Consequently, there is an urgent need for novel antibacterial agents or alternative strategies to combat bacterial infections. Nanoantibiotics encompass a class of nano-antibacterial materials that possess inherent antimicrobial activity or can serve as carriers to enhance drug delivery efficiency and safety. In recent years, metal nanoclusters (M NCs) have gained prominence in the field of nanoantibiotics due to their ultra-small size (less than 3 nm) and distinctive electronic and optical properties, as well as their biosafety features. In this review, we discuss the recent progress of M NCs as a new generation of antibacterial agents. First, the main synthesis methods and characteristics of M NCs are presented. Then, we focus on reviewing various strategies for detecting and treating pathogenic bacterial infections using M NCs, summarizing the antibacterial effects of these nanoantibiotics on wound infections, biofilms, and oral infections. Finally, we propose a perspective on the remaining challenges and future developments of M NCs for bacterial infectious therapy.

Macrocycle-Based Charge Transfer Cocrystals with Dynamically Reversible Chiral Self-Sorting Display Chain Length-Selective Vapochromism to Alkyl Ketones.

Chirality-driven self-sorting plays an essential role in controlling the biofunction of biosystems, such as the chiral double-helix structure of DNA from self-recognition by hydrogen bonding. However, achieving precise control over the chiral self-sorted structures and their functional properties for the bioinspired supramolecular systems still remains a challenge, not to mention realizing dynamically reversible regulation. Herein, we report an unprecedented saucer[4]arene-based charge transfer (CT) cocrystal system with dynamically reversible chiral self-sorting synergistically induced by chiral triangular macrocycle and organic vapors. It displays efficient chain length-selective vapochromism toward alkyl ketones due to precise modulation of optical properties by vapor-induced diverse structural transformations. Experimental and theoretical studies reveal that the unique vapochromic behavior is mainly attributed to the formation of homo- or heterochiral self-sorted assemblies with different alkyl ketone guests, which differ dramatically in solid-state superstructures and CT interactions, thus influencing their optical properties. This work highlights the essential role of chiral self-sorting in controlling the functional properties of synthetic supramolecular systems, and the rarely seen controllable chiral self-sorting at the solid-vapor interface deepens the understanding of efficient vapochromic sensors.

Enrooted-Type Metal-Support Interaction Boosting Oxygen Evolution Reaction in Acidic Media.

Supported metal catalysts with appropriate metal-support interactions (MSIs) hold a great promise for heterogeneous catalysis. However, ensuring tight immobilization of metal clusters/nanoparticles on the support while maximizing the exposure of surface active sites remains a huge challenge. Herein, we report an Ir/WO3 catalyst with a new enrooted-type MSI in which Ir clusters are, unprecedentedly, atomically enrooted into the WO3 lattice. The enrooted Ir atoms decrease the electron density of the constructed interface compared to the adhered (root-free) type, thereby achieving appropriate adsorption toward oxygen intermediates, ultimately leading to high activity and stability for oxygen evolution in acidic media. Importantly, this work provides a new enrooted-type supported metal catalyst, which endows suitable MSI and maximizes the exposure of surface active sites in contrast to the conventional adhered, embedded, and encapsulated types.

Crystal Engineering of MOF-Derived Bimetallic Oxide Solid Solution Anchored with Au Nanoparticles for Photocatalytic CO2 Reduction to Syngas and C2 Hydrocarbons.

Considering that CO2 reduction is mostly a multielectron reaction, it is necessary for the photocatalysts to integrate multiple catalytic sites and cooperate synergistically to achieve efficient photocatalytic CO2 reduction to various products, such as C2 hydrocarbons. Herein, through crystal engineering, we designed and constructed a metal-organic framework-derived Zr/Ti bimetallic oxide solid solution support, which was confirmed by X-ray diffraction, electron microscopy and X-ray absorption spectroscopy. After anchoring Au nanoparticles, the composite photocatalyst exhibited excellent performances toward photocatalytic CO2 reduction to syngas (H2 and CO production rates of 271.6 and 260.6 µmol g-1 h-1) and even C2 hydrocarbons (C2H4 and C2H6 production rates of 6.80 and 4.05 µmol g-1 h-1). According to the control experiments and theoretical calculations, the strong interaction between bimetallic oxide solid solution support and Au nanoparticles was found to be beneficial for binding intermediates and reducing CO2 reduction, highlighting the synergy effect of the catalytic system with multiple active sites.

Superionic Conducting Halide Frameworks Enabled by Interface-Bonded Halides.

The revival of ternary halides Li-M-X (M = Y, In, Zr, etc.; X = F, Cl, Br) as solid-state electrolytes (SSEs) shows promise in realizing practical solid-state batteries due to their direct compatibility toward high-voltage cathodes and favorable room-temperature ionic conductivities. Most of the reported superionic halide SSEs have a structural pattern of [MCl6]x- octahedra and generate a tetrahedron-assisted Li+ ion diffusion pathway. Here, we report a new class of zeolite-like halide frameworks, SmCl3, for example, in which 1-dimensional channels are enclosed by [SmCl9]6- tricapped trigonal prisms to provide a short jumping distance of 2.08 Å between two octahedra for Li+ ion hopping. The fast Li+ diffusion along the channels is verified through ab initio molecular dynamics simulations. Similar to zeolites, the SmCl3 framework can be grafted with halide species to obtain mobile ions without altering the base structure, achieving an ionic conductivity over 10-4 S cm-1 at 30 °C with LiCl as the adsorbent. Moreover, the universality of the interface-bonding behavior and ionic diffusion in a class of framework materials is demonstrated. It is suggested that the ionic conductivity of the MCl3/halide composite (M = La-Gd) is likely in correlation with the ionic conductivity of the grafted halide species, interfacial bonding, and framework composition/dimensions. This work reveals a potential class of halide structures for superionic conductors and opens up a new frontier for constructing zeolite-like frameworks in halide-based materials, which will promote the innovation of superionic conductor design and contribute to a broader selection of halide SSEs.

Revealing Structural Insights of Solid Electrolyte Interphase in High-Concentrated Non-Flammable Electrolyte for Li Metal Batteries by Cryo-TEM.

High-concentrated non-flammable electrolytes (HCNFE) in lithium metal batteries prevent thermal runaway accidents, but the microstructure of their solid electrolyte interphase (SEI) remains largely unexplored, due to the lack of direct imaging tools. Herein, cryo-HRTEM is applied to directly visualize the native state of SEI at the atomic scale. In HCNFE, SEI has a uniform laminated crystalline-amorphous structure that can prevent further reaction between the electrolyte and lithium. The inorganic SEI component, Li2 S2 O7 , is precisely identified by cryo-HRTEM. Density functional theory (DFT) calculations demonstrate that the final Li2 S2 O7 phase has suitable natural transmission channels for Li-ion diffusion and excellent ionic conductivity of 1.2 × 10-5 S cm-1 .

Microbial production of trans-aconitic acid.

Trans-aconitic acid (TAA) is a promising bio-based chemical with the structure of unsaturated tricarboxylic acid, and also has the potential to be a non-toxic nematicide as a potent inhibitor of aconitase. However, TAA has not been commercialized because the traditional production processes of plant extraction and chemical synthesis cannot achieve large-scale production at a low cost. The availability of TAA is a serious obstacle to its widespread application. In this study, we developed an efficient microbial synthesis and fermentation production process for TAA. An engineered Aspergillus terreus strain producing cis-aconitic acid and TAA was constructed by blocking itaconic acid biosynthesis in the industrial itaconic acid-producing strain. Through heterologous expression of exogenous aconitate isomerase, we further designed a more efficient cell factory to specifically produce TAA. Subsequently, the fermentation process was developed and scaled up step-by-step, achieving a TAA titer of 60 g L-1 at the demonstration scale of a 20 m3 fermenter. Finally, the field evaluation of the produced TAA for control of the root-knot nematodes was performed in a field trial, effectively reducing the damage of the root-knot nematode. Our work provides a commercially viable solution for the green manufacturing of TAA, which will significantly facilitate biopesticide development and promote its widespread application as a bio-based chemical.

The discovery of cyclic γ-AApeptides as the promising ligands targeting EP2.

EP2 is a G protein-coupled receptor for prostaglandin E2 (PGE2) derived from cell membrane-released arachidonic acid upon various harmful and injurious stimuli. It is commomly upregulated in tumors and injured brain tissues, as its activation by PGE2 is widely believed to be involved in the pathophysiological mechanisms underlying these conditions via promoting pro-inflammatory reactions. Herein, we report the discovery of two novel macrocyclic peptidomimetics based on the screening of a cyclic γ-AApeptides combinatorial library. These two cyclic γ-AApeptides showed excellent binding affinity with the EP2 protein, and they may lead to the development of novel therapeutic agents and/or molecular probes to modulate the PGE2/EP2 signaling.

Na-K Alloy Anode for High-Performance Solid-State Sodium Metal Batteries.

Rechargeable solid-state Na metal batteries (SSNMB) can offer high operational safety and energy density. However, poor solid-solid contact between the electrodes and the electrolyte can dramatically increase interfacial resistance and Na dendrite formation, even at low current rates. Therefore, we developed a carbon-fiber-supported liquid Na-K alloy anode that ensures close anode-electrolyte contact, enabling superior cycle stability and rate capability. We then demonstrated the first cryogenic transmission electron microscopy (cryo-TEM) characterization of an SSNMB, capturing the evolution of solid-electrolyte interphase (SEI) and revealing both crystalline and amorphous phases, which could facilitate ion transport and prevent continuous side reactions. By enhancing contact between the Na-K alloy and solid-state electrolyte, these symmetric cells are capable of cycling for over 800 h without notable increased polarization and enable an unprecedented critical current density (CCD) at 40 mA cm-2. Our liquid Na-K alloy approach offers a promising strategic avenue toward commercial SSNMBs.

Bismuth Ferrite as an Electrocatalyst for the Electrochemical Nitrate Reduction.

Electrochemical nitrate reduction has become an appealing "waste-to-wealth" approach for sustainable NH3 synthesis owing to its mild operating conditions. However, developing catalysts with high activities and Faradaic efficiencies for this complicated eight-electron reaction is a great challenge. Herein, bismuth ferrite (BiFeO3) flakes, with a distorted perovskite-type structure, are demonstrated to be excellent catalysts for electrochemical NH3 synthesis via nitrate reduction, with a maximum Faradaic efficiency of 96.85%, NH3 yield of 90.45 mg h-1 mgcat-1, at -0.6 V vs. reversible hydrogen electrode. During the nitrate reduction reaction, the crystalline BiFeO3 rapidly converts into an amorphous phase, which is stable in the long term reaction. These results open a new window for rational design of more active and durable electrocatalysts.

Enabling Ultrastable Alkali Metal Anodes by Artificial Solid Electrolyte Interphase Fluorination.

The high specific capacity of alkalic metal (Li, Na, and K) anodes has drawn widespread interest; however, the practical applications of alkalic metal anodes have been hampered by dendrite growth and interfacial instability, resulting in performance deterioration and even safety issues. Here, we describe a simple method for building tunable fluoride-based artificial solid-electrolyte interphase (SEI) from the fluorination reaction of alkali metals with a mild organic fluorinating reagent. Comprehensive characterization by advanced electron microscopes shows that the LiF-based artificial SEI adopts a crystal-glass structure, which enables efficient Li ion transport and improves structural integrity against the volume changes that occur during Li plating/stripping. Compared with bare Li anode, the ones with artificial SEI exhibit decreased voltage hysteresis, enhanced rate capability, and prolonged cycle life. This method is also applied to generate fluoride-based artificial SEI on Na and K metal anodes that brings significant improvement in battery performance.