Clinical Analysis of Inhaled Nitric Oxide Therapy in Preterm Infants at Different Gestational Ages: A National Retrospective Multicenter Study.

OBJECTIVE: This study aimed to investigate clinical features of inhaled nitric oxide (iNO) in preterm infants with a gestational age (GA) < 34 weeks in China. STUDY DESIGN: The clinical data of 434 preterm infants with GA < 34 weeks, treated with iNO in the neonatology departments of eight Class A tertiary hospitals in China over a 10-year period from January 2013 to December 2022, were included in this retrospective multicenter investigation. The infants were divided into three groups based on GA: 24 to 27 weeks (extremely preterm infants), 28 to 31 weeks (very preterm infants), and 32 to 33 weeks (moderate preterm infants). The use of iNO, perinatal data, incidence and mortality of indication for iNO treatment, therapeutic effects of iNO, incidence of short-term complications for iNO treatment, and mortality were compared among these three groups. RESULTS: Over the past 10 years, the proportion of iNO use was highest in extremely preterm infants each year. The lower the GA, the higher the iNO use rate: 4.20% for GA 24 to 27 weeks, 1.54% for GA 28 to 31 weeks, and 0.85% for GA 32 to 33 weeks. There was no significant difference in the therapeutic effect of iNO among the three groups. The incidence of neonatal pulmonary hemorrhage, neonatal shock, late-onset diseases, retinopathy of prematurity requiring intervention, intracranial hemorrhage (grade 3 or 4), periventricular leukomalacia, neonatal necrotizing enterocolitis (≥stage II), and moderate to severe bronchopulmonary dysplasia was highest in extremely preterm infants and increased with decreasing GA. Mortality was negatively correlated with GA and birth weight. The highest rate of iNO treatment in 24 to 27 weeks' preterm infants was due to hypoxic respiratory failure (HRF), whereas the highest rate of iNO treatment in 32 to 33 weeks' preterm infants was due to documented persistent pulmonary hypertension of the newborn (PPHN). The rates of iNO treatment due to HRF and documented PPHN were 54.3 and 60.6%, respectively, in extremely preterm infants, significantly higher than in very preterm and moderate preterm infants (all p < 0.05). Within the same GA group, the proportion of preterm infants treated with iNO for HRF was lower than that for documented PPHN (all p < 0.05), but there was no statistically significant difference in mortality between HRF and documented PPHN treated with iNO (all p > 0.05). CONCLUSION: Among preterm infants with GA < 34 weeks, the rate of iNO usage was highest in extremely preterm infants. However, iNO failed to improve the clinical outcome of extremely preterm infants with refractory hypoxemia, and there was no significant difference in the therapeutic effect of iNO among preterm infants with different GAs.

Engineering the novel azobenzene-based molecular photoswitches for suppressing bacterial infection through dynamic regulation of biofilm formation.

BACKGROUND: Bacterial biofilm is a strong fortress for bacteria to resist harsh external environments, which can enhance their tolerance and exacerbate the drug/pesticide resistance risk. Currently, photopharmacology provides an advanced approach via precise spatiotemporal control for regulating biological activities by light-controlling the molecular configurations, thereby having enormous potential in the development of drug/pesticides. RESULTS: To further expand the photopharmacology application for discovering new antibiofilm agents, we prepared a series of light-controlled azo-active molecules and explored their photo isomerization, fatigue resistance, and anti-biofilm performance. Furthermore, their mechanisms of inhibiting biofilm formation were systematically investigated. Overall, designed azo-derivative A11 featured excellent anti-Xoo activity with an half-maximal effective concentration (EC50) value of 5.45 µg mL-1, and the EC50 value could be further elevated to 2.19 µg mL-1 after ultraviolet irradiation (converted as cis-configuration). The photo-switching behavior showed that A11 had outstanding anti-fatigue properties. An in-depth analysis of the action mechanism showed that A11 could effectively inhibit biofilm formation and the expression of relevant virulence factors. This performance could be dynamically regulated via loading with private light-switch property. CONCLUSION: In this work, designed light-controlled azo molecules provide a new model for resisting bacterial infection via dynamic regulation of bacterial biofilm formation. © 2024 Society of Chemical Industry.

Activity-based protein profiling guided new target identification of quinazoline derivatives for expediting bactericide discovery: Activity-based protein profiling derived new target discovery of antibacterial quinazolines.

INTRODUCTION: The looming antibiotic-resistance problem has imposed an enormous crisis on global public health and agricultural development. Even worse, the evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens have made the resurgence of diseases that were once easily treatable deadly again. The development of antibiotics with novel mechanisms of action is urgently required. OBJECTIVES: Inspired by charming activity-based protein profiling (ABPP) technology and increasing attention to quinazolines in the development of antibacterial agents, this study engineered a series of new quinazoline derivatives, assessed their antibacterial profiles, and first identified the possible target. METHODS: The target identification and their possible binding sites were verified by ABPP technology, molecular docking, and molecular dynamic simulations. The fatty acid synthesis process was analyzed by gas chromatography, propidium iodide staining, and scanning electron microscopy. The physicochemical properties and fungicide-likeness were evaluated using the Fungicide Physicochemical-properties Analysis Database. RESULTS: Compound 7a, an acrylamide-functionalized quinazoline derivative, exhibited excellent antibacterial potency against Xanthomonas oryzae pv. oryzae with an EC50 value of 13.20 µM. More importantly, ABPP technology showed that ß-ketoacyl-ACP-synthase Ⅱ (FabF) was the first identified quinazolines' potential target. Compound 7a could selectively bind to the Cys151 residue of FabF through covalent interaction, suppress fatty acid biosynthesis, and damage the cell membrane integrity, thereby killing the bacteria. The pot experiment results showed that compound 7a demonstrated protective and curative values of 49.55 % and 47.46 %, surpassing controls bismerthiazol and thiodiazole copper. Finally, compound 7a exhibited low toxicity towards non-target organisms. These unprecedented performances contributed to excavating new quinazoline-based bactericidal agents. CONCLUSION: Our research highlights the superiority of ABPP technology, for the first time, identifies the target of engineered quinazolines in pathogenic bacteria, and their potential target fished by ABPP tools holds great promise for the development of quinazoline-based and/or FabF-targeted bactericides.

CTBP1 links metabolic syndrome to polycystic ovary syndrome through interruption of aromatase and SREBP1.

Some patients with polycystic ovarian syndrome (PCOS) suffered from metabolic syndrome (MetS) including dyslipidemia, hyperinsulinism, but the underlying mechanism is unclear. Although C-terminal Binding Protein 1 (CTBP1) is a transcriptional co-repressor frequently involved in hormone secretion disorders and MetS-associated diseases, the role of CTBP1 in PCOS is rarely reported. In the present study, we found that CTBP1 expression was significantly elevated in primary granulosa cells (pGCs) derived from the PCOS with MetS patients and was positively associated with serum triglyceride, but negatively correlated with serum estradiol (E2) or high-density lipoprotein. Mechanistic study suggested that CTBP1 physically bound to the promoter II of cytochrome P450 family 19 subfamily A member 1 (CYP19A1) to inhibit the aromatase gene transcription and expression, resulting in the reduced E2 synthesis. Moreover, CTBP1 interacted with the phosphorylated SREBP1a at S396 in nuclei, leading to the FBXW7-dependent protein degradation, resulting in the reduced lipid droplets formation in pGCs. Therefore, we conclude that CTBP1 in GCs dysregulates the synthesis of steroid hormones and lipids through suppression of aromatase expression and promotion of SREBP1a protein degradation in PCOS patients, which may offer some fresh insights into the potential pathological mechanism for this tough disease.

Rational design of a DNA-launched live attenuated vaccine against human enterovirus 71.

Human Enterovirus 71 (EV71) has emerged as one of the predominant causative agents of hand, foot and mouth disease (HFMD) with global impact. Despite the inactivated vaccine being licensed, other vaccine candidates based on advanced technology platforms are under development. In this report, we rationally designed and constructed two DNA-launched live attenuated vaccine candidates (pDL-EV71) under the control of specific promoters. In vitro and in vivo transfection with pDL-EV71 driven by the CMV promoter successfully yielded fully infectious EV71. More importantly, the administration of pDL-EV71 did not cause clinical symptoms following intracranial or intramuscular inoculation in neonatal and IFNα/ßR-/- mice, demonstrating its safety profile. Moreover, a single-dose or two-dose immunization with pDL-EV71 elicited robust neutralizing antibodies against EV71 as well as an antigen-specific cellular response in mice. A single-dose immunization with 10 â€‹µg of pDL-EV71 conferred complete protection against lethal EV71 infection in neonates born to immunized maternal mice. Overall, our present results demonstrate that pDL-EV71 is a safe and effective vaccine candidate against EV71 for further development.

Wet-dry or freeze-thaw alternation can regulate the impacts of farmland plastic pollution on soil bacterial communities and functions.

The persistence of farmland plastic pollution has raised significant concerns regarding its potential long-term impacts on soil health in the context of global climate change. However, there are still gaps in the understanding of the impacts of plastic residues on soil microbial communities and functions in agricultural environments under unstable and extreme climatic conditions. In this study, the effects of plastic residues (two types and three shapes) on farmland soil bacterial communities and functions across varying environmental conditions were investigated through microscopic experiments. The results revealed that plastic residues subjected to wet-dry or freeze-thaw alternations exhibited greater degradation compared to those under natural conditions. The effects of plastic residue types and shapes on soil bacterial diversity and function were regulated by environmental factors. The plastic residues significantly reduced the stability of the bacterial network under natural condition (P < 0.05), whereas the opposite phenomenon was observed under wet-dry or freeze-thaw alternating conditions. Compared to under natural condition, lower numbers of bacterial functional pathways exhibiting significant differences due to plastic residues were observed under wet-dry or freeze-thaw alternating conditions. Significant associations were observed between soil bacterial communities and functions and various soil physicochemical properties under natural conditions (P < 0.05), and most of these associations were attenuated in the wet-dry or freeze-thaw alternations. This study demonstrated the potential impacts of plastic pollution on farmland soil microbiomes, which could be modulated by both residue characteristics and climatic conditions. Specifically, extreme environments could mitigate plastic-pollution-driven influences on soil microbiomes.

Application of Lactiplantibacillus plantarum hydrogel coating in combination with ice temperature for the preservation of fresh yak meat.

Fresh yak meat is highly nutritious and prone to spoilage, so developing suitable preservation methods is crucial. In this study, hydrogel coatings composed of konjac glucomannan, Lactiplantibacillus plantarum and gallic acid (KGX) were applied to preserve fresh yak meat under ice temperature (-1 °C). After 16 days, KGX group showed lowest total viable count (5.3 ± 0.1 log cfu/g) and total volatile basic nitrogen (13.02 ± 1.40 mg/100 g), which did not exceed the relevant standards of fresh meat. Combined assessments of color, texture, pH, drip loss rate, and thiobarbituric acid reactive substances indicated that KGX coating effectively prolonged yak meat preservation. High-throughput sequencing revealed that KGX coating effectively reduced the abundance of Pseudomonas and Candida. The application of L. plantarum hydrogel coatings in conjunction with ice temperature increased the shelf life of fresh yak meat to 16-20 days, suggesting its potential as a viable preservation method for fresh meat.

Monocyte/macrophage-mediated venous thrombus resolution.

Venous thromboembolism (VTE) poses a notable risk of morbidity and mortality. The natural resolution of the venous thrombus might be a potential alternative treatment strategy for VTE. Monocytes/macrophages merge as pivotal cell types in the gradual resolution of the thrombus. In this review, the vital role of macrophages in inducing inflammatory response, augmenting neovascularization, and facilitating the degradation of fibrin and collagen during thrombus resolution was described. The two phenotypes of macrophages involved in thrombus resolution and their dual functions were discussed. Macrophages expressing various factors, including cytokines and their receptors, adhesion molecules, chemokine receptors, vascular endothelial growth factor receptors, profibrinolytic- or antifibrinolytic-related enzymes, and other elements, are explored for their potential to promote or attenuate thrombus resolution. Furthermore, this review provides a comprehensive summary of new and promising therapeutic candidate drugs associated with monocytes/macrophages that have been demonstrated to promote or impair thrombus resolution. However, further clinical trials are essential to validate their efficacy in VTE therapy.

Simultaneous aerobic nitrogen and phosphorus removal by novel halotolerant fungus Mucor circinelloides SNDM1: Function and metabolism pathway.

Fungi capable of simultaneous nitrogen and phosphorus removal from wastewater is rarely found. Here, a novel fungal strain (SNDM1) performing heterotrophic nitrification, aerobic denitrification, and phosphate removal was isolated and identified as Mucor circinelloides. The favorable nutrient removal conditions by the strain using glucose were C/N ratios of 25-30, salinities of 0 %-3 %, and pH of 7.5. Strain SNDM1 achieved ammonium, nitrite, nitrate, and phosphate removal rates of 5.23, 10.08, 4.88, and 0.97 mg/L/h. Nitrogen balance indicated that gaseous (18.60 %-24.55 %) and intracellular nitrogen (43.76 %-70.63 %) were primary fate of initial nitrogen. Enzyme activity revealed that ammonium removal occurred through heterotrophic nitrification and aerobic denitrification. Removed phosphorus was mainly transformed into cell membranes (56 %-64 %) and extracellular polymeric substances (20 %-26 %). Orthophosphate was the major intracellular phosphorus species, while polyphosphate and pyrophosphate existed extracellularly. These findings highlight the potential of this fungal strain for bioremediating polluted wastewater.

Gut microbiota contributes to high-altitude hypoxia acclimatization of human populations.

BACKGROUND: The relationship between human gut microbiota and high-altitude hypoxia acclimatization remains highly controversial. This stems primarily from uncertainties regarding both the potential temporal changes in the microbiota under such conditions and the existence of any dominant or core bacteria that may assist in host acclimatization. RESULTS: To address these issues, and to control for variables commonly present in previous studies which significantly impact the results obtained, namely genetic background, ethnicity, lifestyle, and diet, we conducted a 108-day longitudinal study on the same cohort comprising 45 healthy Han adults who traveled from lowland Chongqing, 243 masl, to high-altitude plateau Lhasa, Xizang, 3658 masl, and back. Using shotgun metagenomic profiling, we study temporal changes in gut microbiota composition at different timepoints. The results show a significant reduction in the species and functional diversity of the gut microbiota, along with a marked increase in functional redundancy. These changes are primarily driven by the overgrowth of Blautia A, a genus that is also abundant in six independent Han cohorts with long-term duration in lower hypoxia environment in Shigatse, Xizang, at 4700 masl. Further animal experiments indicate that Blautia A-fed mice exhibit enhanced intestinal health and a better acclimatization phenotype to sustained hypoxic stress. CONCLUSIONS: Our study underscores the importance of Blautia A species in the gut microbiota's rapid response to high-altitude hypoxia and its potential role in maintaining intestinal health and aiding host adaptation to extreme environments, likely via anti-inflammation and intestinal barrier protection.

Comparative study of the clinical value of digital subtraction angiography via femoral and radial arterial paths.

OBJECTIVE: To evaluate the clinical efficacy of digital subtraction angiography (DSA) performed via femoral artery and radial artery approaches. METHODS: This retrospective study included 480 patients requiring cerebral vascular angiography at the First People's Hospital of Changde City from March 2020 to February 2022. Patients were divided into the femoral artery group (transfemoral approach, n=400) and the radial artery group (transradial approach, n=80) according to the surgical route. We compared perioperative metrics, success rates of selective angiography and puncture, and complication rates (including pseudoaneurysm, urinary retention, hematoma, vasospasm) between the groups. Multivariate logistic regression was used to analyze factors influencing the failure of angiography by each approach. RESULTS: The radial artery group exhibited shorter durations for puncture, hemostasis, exposure, operation, and postoperative recovery (all P<0.001). The success rate of selective angiography was higher in the radial artery group (93.75%) compared to the femoral artery group (85.25%) (χ2=4.168, P=0.041). No significant difference was found in puncture success rates between the groups (χ2=0.235, P=0.628). The overall complication rate was significantly lower in the radial artery group (2.50%) compared to the femoral artery group (9.25%) (χ2=4.069, P=0.044). Gender and low-density lipoprotein cholesterol levels were significant predictors of angiography failure in both approaches (both P<0.05). CONCLUSION: The transradial approach for DSA is safe and feasible, offering advantages in terms of operational time and complication rates, making it the preferred method in clinical settings.

Pterostilbene improves neurological dysfunction and neuroinflammation after ischaemic stroke via HDAC3/Nrf1-mediated microglial activation.

BACKGROUND: Stroke is a type of acute brain damage that can lead to a series of serious public health challenges. Demonstrating the molecular mechanism of stroke-related neural cell degeneration could help identify a more efficient treatment for stroke patients. Further elucidation of factors that regulate microglia and nuclear factor (erythroid-derived 2)-like 1 (Nrf1) may lead to a promising strategy for treating neuroinflammation after ischaemic stroke. In this study, we investigated the possible role of pterostilbene (PTS) in Nrf1 regulation in cell and animal models of ischaemia stroke. METHODS: We administered PTS, ITSA1 (an HDAC activator) and RGFP966 (a selective HDAC3 inhibitor) in a mouse model of middle cerebral artery occlusion-reperfusion (MCAO/R) and a model of microglial oxygen‒glucose deprivation/reperfusion (OGD/R). The brain infarct size, neuroinflammation and microglial availability were also determined. Dual-luciferase reporter, Nrf1 protein stability and co-immunoprecipitation assays were conducted to analyse histone deacetylase 3 (HDAC3)/Nrf1-regulated Nrf1 in an OGD/R-induced microglial injury model. RESULTS: We found that PTS decreased HDAC3 expression and activity, increased Nrf1 acetylation in the cell nucleus and inhibited the interaction of Nrf1 with p65 and p65 accumulation, which reduced infarct volume and neuroinflammation (iNOS/Arg1, TNF-α and IL-1ß levels) after ischaemic stroke. Furthermore, the CSF1R inhibitor PLX5622 induced elimination of microglia and attenuated the therapeutic effect of PTS following MCAO/R. In the OGD/R model, PTS relieved OGD/R-induced microglial injury and TNF-α and IL-1ß release, which were dependent on Nrf1 acetylation through the upregulation of HDAC3/Nrf1 signalling in microglia. However, the K105R or/and K139R mutants of Nrf1 counteracted the impact of PTS in the OGD/R-induced microglial injury model, which indicates that PTS treatment might be a promising strategy for ischaemia stroke therapy. CONCLUSION: The HDAC3/Nrf1 pathway regulates the stability and function of Nrf1 in microglial activation and neuroinflammation, which may depend on the acetylation of the lysine 105 and 139 residues in Nrf1. This mechanism was first identified as a potential regulatory mechanism of PTS-based neuroprotection in our research, which may provide new insight into further translational applications of natural products such as PTS.

FXR activation remodels hepatic and intestinal transcriptional landscapes in metabolic dysfunction-associated steatohepatitis.

The escalating obesity epidemic and aging population have propelled metabolic dysfunction-associated steatohepatitis (MASH) to the forefront of public health concerns. The activation of FXR shows promise to combat MASH and its detrimental consequences. However, the specific alterations within the MASH-related transcriptional network remain elusive, hindering the development of more precise and effective therapeutic strategies. Through a comprehensive analysis of liver RNA-seq data from human and mouse MASH samples, we identified central perturbations within the MASH-associated transcriptional network, including disrupted cellular metabolism and mitochondrial function, decreased tissue repair capability, and increased inflammation and fibrosis. By employing integrated transcriptome profiling of diverse FXR agonists-treated mice, FXR liver-specific knockout mice, and open-source human datasets, we determined that hepatic FXR activation effectively ameliorated MASH by reversing the dysregulated metabolic and inflammatory networks implicated in MASH pathogenesis. This mitigation encompassed resolving fibrosis and reducing immune infiltration. By understanding the core regulatory network of FXR, which is directly correlated with disease severity and treatment response, we identified approximately one-third of the patients who could potentially benefit from FXR agonist therapy. A similar analysis involving intestinal RNA-seq data from FXR agonists-treated mice and FXR intestine-specific knockout mice revealed that intestinal FXR activation attenuates intestinal inflammation, and has promise in attenuating hepatic inflammation and fibrosis. Collectively, our study uncovers the intricate pathophysiological features of MASH at a transcriptional level and highlights the complex interplay between FXR activation and both MASH progression and regression. These findings contribute to precise drug development, utilization, and efficacy evaluation, ultimately aiming to improve patient outcomes.

Effect of dapagliflozin on uric acid in patients with chronic heart failure and hyperuricemia.

BACKGROUND: Patients with chronic heart failure (CHF) frequently develop hyperuricemia, an elevated serum uric acid level, associated with adverse outcomes. Dapagliflozin, a sodium-glucose cotransporter-2 inhibitor, demonstrates reduction in cardiovascular mortality and hospitalization in patients with CHF and ejection fraction (HFrEF), irrespective of diabetes. However, dapagliflozin's effect on the uric acid levels in patients with CHF and hyperuricemia remain unclear. AIM: To investigate the effects of dapagliflozin on uric acid levels in CHF patients with hyperuricemia. METHODS: We conducted a randomized, double-blind, placebo-controlled trial in 200 patients with CHF and hyperuricemia, with HFrEF and serum uric acid levels ≥ 7 mg/dL (≥ 416 µmol/L). The participants were randomly assigned to receive a daily dose of 10 mg dapagliflozin or placebo for 24 months. The primary endpoint was the change in serum uric acid level from baseline to 24 months. Secondary endpoints included changes in left ventricular ejection fraction (LVEF), N-terminal pro-B-type natriuretic peptide (NT-proBNP), and quality of life (QoL) scores, as well as the incidence of cardiovascular death and hospitalization for heart failure. RESULTS: At 24 months, dapagliflozin significantly reduced serum uric acid levels by 1.2 mg/dL (71 µmol/L) compared with placebo (95%CI: -1.5 to -0.9; P < 0.001). Dapagliflozin also significantly improved LVEF by 3.5% (95%CI: 2.1-4.9; P < 0.001), NT-proBNP by 25% (95%CI: 18-32; P < 0.001), and QoL scores by 10 points (95%CI: 7-13; P < 0.001) and reduced the risk of cardiovascular death and hospitalization for heart failure by 35% (95%CI: 15-50; P = 0.002) compared with the placebo. Adverse events were similar between the two groups, except for a higher rate of genital infections in the dapagliflozin group (10% vs 2%, P = 0.01). CONCLUSION: Dapagliflozin significantly lowered serum uric acid levels and improved the clinical outcomes in patients with CHF and hyperuricemia. Therefore, dapagliflozin may be a useful therapeutic option for this high-risk population.

Breaking the barrier: Nanoparticle-enhanced radiotherapy as the new vanguard in brain tumor treatment.

The pursuit of effective treatments for brain tumors has increasingly focused on the promising area of nanoparticle-enhanced radiotherapy (NERT). This review elucidates the context and significance of NERT, with a particular emphasis on its application in brain tumor therapy-a field where traditional treatments often encounter obstacles due to the blood-brain barrier (BBB) and tumor cells' inherent resistance. The aims of this review include synthesizing recent advancements, analyzing action mechanisms, and assessing the clinical potential and challenges associated with nanoparticle (NP) use in radiotherapy enhancement. Preliminary preclinical studies have established a foundation for NERT, demonstrating that nanoparticles (NPs) can serve as radiosensitizers, thereby intensifying radiotherapy's efficacy. Investigations into various NP types, such as metallic, magnetic, and polymeric, have each unveiled distinct interactions with ionizing radiation, leading to an augmented destruction of tumor cells. These interactions, encompassing physical dose enhancement and biological and chemical radio sensitization, are crucial to the NERT strategy. Although clinical studies are in their early phases, initial trials have shown promising results in terms of tumor response rates and survival, albeit with mindful consideration of toxicity profiles. This review examines pivotal studies affirming NERT's efficacy and safety. NPs have the potential to revolutionize radiotherapy by overcoming challenges in targeted delivery, reducing off-target effects, and harmonizing with other modalities. Future directions include refining NP formulations, personalizing therapies, and navigating regulatory pathways. NERT holds promise to transform brain tumor treatment and provide hope for patients.

Electrolyte Composition-Dependent Product Selectivity in CO2 Reduction with a Porphyrinic Metal-Organic Framework Catalyst.

A copper porphyrin-derived metal-organic framework electrocatalyst, FICN-8, was synthesized and its catalytic activity for CO2 reduction reaction (CO2RR) was investigated. FICN-8 selectively catalyzed electrochemical reduction of CO2 to CO in anhydrous acetonitrile electrolyte. However, formic acid became the dominant CO2RR product with the addition of a proton source to the system. Mechanistic studies revealed the change of major reduction pathway upon proton source addition, while catalyst-bound hydride (*H) species was proposed as the key intermediate for formic acid production. This work highlights the importance of electrolyte composition on CO2RR product selectivity.

Activity-based protein profiling in drug/pesticide discovery: Recent advances in target identification of antibacterial compounds.

Given the escalating incidence of bacterial diseases and the challenge posed by pathogenic bacterial resistance, it is imperative to identify appropriate methodologies for conducting proteomic investigations on bacteria, and thereby promoting the target-based drug/pesticide discovery. Interestingly, a novel technology termed "activity-based protein profiling" (ABPP) has been developed to identify the target proteins of active molecules. However, few studies have summarized advancements in ABPP for identifying the target proteins in antibacterial-active compounds. In order to accelerate the discovery and development of new drug/agrochemical discovery, we provide a concise overview of ABPP and its recent applications in antibacterial agent discovery. Diversiform cases were cited to demonstrate the potential of ABPP for target identification though highlighting the design strategies and summarizing the reported target protein of antibacterial compounds. Overall, this review is an excellent reference for probe design towards antibacterial compounds, and offers a new perspective of ABPP in bactericide development.

Application of natural-products repurposing strategy to discover novel FtsZ inhibitors: Bactericidal evaluation and the structure-activity relationship of sanguinarine and its analogs.

The novel bactericidal target-filamentous temperature-sensitive protein Z (FtsZ)-has drawn the attention of pharmacologists to address the emerging issues with drug/pesticide resistance caused by pathogenic bacteria. To enrich the structural diversity of FtsZ inhibitors, the antibacterial activity and structure-activity relationship (SAR) of natural sanguinarine and its analogs were investigated by using natural-products repurposing strategy. Notably, sanguinarine and chelerythrine exerted potent anti-Xanthomonas oryzae pv. oryzae (Xoo) activity, with EC50 values of 0.96 and 0.93 mg L-1, respectively, among these molecules. Furthermore, these two compounds could inhibit the GTPase activity of XooFtsZ, with IC50 values of 241.49 µM and 283.14 µM, respectively. An array of bioassays including transmission electron microscopy (TEM), fluorescence titration, and Fourier transform infrared spectroscopy (FT-IR) co-verified that sanguinarine and chelerythrine were potential XooFtsZ inhibitors that could interfere with the assembly of FtsZ filaments by inhibiting the GTPase hydrolytic ability of XooFtsZ protein. Additionally, the pot experiment suggested that chelerythrine and sanguinarine demonstrated excellent curative activity with values of 59.52% and 54.76%, respectively. Excitedly, these two natural compounds also showed outstanding druggability, validated by acceptable drug-like properties and low toxicity on rice. Overall, the results suggested that chelerythrine was a new and potential XooFtsZ inhibitor to develop new bactericide and provided important guiding values for rational drug design of FtsZ inhibitors. Notably, our findings provide a novel strategy to discover novel, promising and green bacterial compounds for the management of plant bacterial diseases.

Research Progress of Biosensor Based on Organic Photoelectrochemical Transistor.

In order to solve the food safety problem better, it is very important to develop a rapid and sensitive technology for detecting food contamination residues. Organic photoelectrochemical transistor (OPECT) biosensor rely on the photovoltage generated by a semiconductor upon excitation by light to regulate the conductivity of the polymer channels and realize biosensor analysis under zero gate bias. This technology integrates the excellent characteristics of photoelectrochemical (PEC) bioanalysis and the high sensitivity and inherent amplification ability of organic electrochemical transistor (OECT). Based on this, OPECT biosensor detection has been proven to be superior to traditional biosensor detection methods. In this review, we summarize the research status of OPECT biosensor in disease markers and food residue analysis, the basic principle, classification, and biosensing mechanism of OPECT biosensor analysis are briefly introduced, and the recent applications of biosensor analysis are discussed according to the signal strategy. We mainly introduced the OPECT biosensor analysis methods applied in different fields, including the detection of disease markers and food hazard residues such as prostate-specific antigen, heart-type fatty acid binding protein, T-2 toxin detection in milk samples, fat mass and objectivity related protein, ciprofloxacin in milk. The OPECT biosensor provides considerable development potential for the construction of safety analysis and detection platforms in many fields, such as agriculture and food, and hopes to provide some reference for the future development of biosensing analysis methods with higher selectivity, faster analysis speed and higher sensitivity.

The chemokine CCL14 is a potential biomarker associated with immune cell infiltration in lung adenocarcinoma.

BACKGROUND: Chemokine ligand 14, which has a C-C motif (CCL14), mediates the immunological milieu around tumors. However, its role in the progression of lung adenocarcinoma (LUAD) is still unknown. Our objectives were to study the association between CCL14 and tumor-infiltrating immune cells (TIICs) as well as the predictive significance of CCL14 in LUAD. METHODS: The expression of CCL14 in LUAD was examined by using the Oncomine, The Cancer Genome Atlas (TCGA), The University of Alabama at Birmingham CANcer data analysis Portal (UALCAN), and Human Protein Atlas databases. To determine the prognostic significance of CCL14 in LUAD, researchers used the Kaplan‒Meier plotter and Gene Expression Profiling Interactive Analysis (GEPIA, version 2). We utilized TIMER and GEPIA2 to investigate the connection between CCL14 and TIICs. Gene set enrichment analysis (GSEA) was used to test for functional enrichment of genes. We used RT‒qPCR to measure CCL14 expression and Cell Counting Kit-8, Transwell, and wound healing assays to investigate the biological role of CCL14. RESULTS: The prognosis of patients with LUAD was worse when CCL14 expression was low. Statistical analysis revealed that CCL14 mRNA expression was significantly greater in lung epithelial cells than in LUAD cell lines in vitro. Enhancing CCL14 expression reduced cell migration, invasion, and proliferation. The results of the immune infiltration research showed that CCL14 and TIICs were positively correlated. Different immune infiltration patterns associated with CCL14 were also shown by TIIC markers. According to GSEA, histone deacetylases, G2/M checkpoints, and Notch signaling pathways were associated with low CCL14 expression. CONCLUSIONS: CCL14 is anticipated to emerge as a prognostic marker and therapeutic target for LUAD due to its role in regulating TIICs, suggesting that it may be an antioncogene.