Dopamine and its precursor levodopa inactivate SARS-CoV-2 main protease by forming a quinoprotein.

Many studies show either the absence, or very low levels of, SARS-CoV-2 viral RNA and/or antigen in the brain of COVID-19 patients. Reports consistently indicate an abortive infection phenomenon in nervous cells despite the fact that they contain the SARS-CoV-2 receptor, ACE2. Dopamine levels in different brain regions are in the range of micromolar to millimolar concentrations. We have shown that sub-micromolar to low micromolar concentrations of dopamine or its precursor (levodopa) time- and dose-dependently inhibit the activity of SARS-CoV-2 main protease (Mpro), which is vital for the viral life cycle, by forming a quinoprotein. Thiol detection coupled with the assessment of Mpro activity suggests that among the 12 cysteinyl thiols, the active site, Cys145-SH, is preferentially conjugated to the quinone derived from the oxidation of dopamine or levodopa. LC-MS/MS analyses show that the Cys145-SH is covalently conjugated by dopamine- or levodopa-o-quinone. These findings help explain why SARS-CoV-2 causes inefficient replication in many nerve cell lines. It is well recognized that inhaled pulmonary drug delivery is the most robust therapy pathway for lung diseases. CVT-301 (orally inhaled levodopa) was approved by the FDA as a drug for Parkinson's patients prior to the outbreak of COVID-19 in 2018. Based on the fact that SARS-CoV-2 causes inefficient replication in the CNS with abundant endogenous Mpro inhibitor in addition to the current finding that levodopa has an Mpro-inhibitory effect somewhat stronger than dopamine, we should urgently investigate the use of CVT-301 as a lung-targeting, COVID-19, Mpro inhibitor.

Single-port-plus-one robot-assisted laparoscopic Lich-Gregoir direct nipple ureteral extravesical reimplantation in pediatric primary obstructive megaureter, comparing to laparoscopic cohen.

PURPOSE: To compare the effects of a single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple approach and traditional laparoscopic Cohen in treating pediatric primary obstructive megaureter. MATERIALS AND METHODS: The clinical data of 24 children with primary obstructive megaureter from January 2021 to November 2021 were analyzed retrospectively. Among them, 12 children (8 boys and 4 girls, the average age were 17.17 ± 6.31 months) treated with the laparoscopic Cohen method were defined as group C. The remaining 12 children (7 boys and 5 girls, the average age was 17.33 ± 6.99 months) underwent single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple ureteral extravesical reimplantation were defined as group L. The parameters of pre-operation, intraoperative and postoperative were compared. RESULTS: There were no differences in the patient characteristics and average follow-up time between the two groups (P > 0.05).The obstruction resolution rate was 100% in both groups. The total operation time in group L is slightly longer than that in group C(P < 0.001),but the intraperitoneal operation time of the two groups was comparable(P > 0.05). The postoperative parameters included blood loss, gross haematuria time, indwelling catheterization time and hospitalization time in group L is shorter than group C(P < 0.05). One year post-operation, decreasing in ureteral diameter and APRPD, and increasing in DRF were remarkably observed in both two groups(P < 0.05). Ureteral diameter, APRPD, and DRF were not significantly different both in pre-operation and post-operation between Group L and Group C(P > 0.05). CONCLUSION: Single-port-plus-one robot-assisted laparoscopic-modified Lich-Gregoir direct nipple approach and traditional laparoscopic Cohen are both dependable techniques for ureteral reimplantation in the treatment of pediatric primary obstructive megaureter. Since Lich-Gregoir can preserve the physiological direction of the ureter and direct nipple reimplantation enhances the effect of anti-refluxing, this technique is favorable for being promoted and applied in robot surgery.

An explainable multiscale LSTM model with wavelet transform and layer-wise relevance propagation for daily streamflow forecasting.

Developing an accurate and reliable daily streamflow forecasting model is important for facilitating the efficient resource planning and management of hydrological systems. In this study, an explainable multiscale long short-term memory (XM-LSTM) model is proposed for effective daily streamflow forecasting by integrating the à trous wavelet transform (ATWT) for decomposing data, the Boruta algorithm for identifying model inputs, and the layer-wise relevance propagation (LRP) for explaining the prediction results. The proposed XM-LSTM is tested by performing multi-step-ahead forecasting of daily streamflow at four stations in the middle and lower reaches of the Yangtze River basin and compared with the X-LSTM. The X-LSTM is formed by coupling the long short-term memory (LSTM) with the LRP. For comparison, the inputs of these two models are identified by the Boruta selection algorithm. The results show that all models exhibit good ability to forecast daily streamflow, however, the prediction performance decreases as the lead time increases. The XM-LSTM provides a better forecasting performance than the X-LSTM, suggesting the ability of the ATWT to improve the LSTM for daily streamflow forecasting. Moreover, the correlation scores analysis by the LRP shows that the ATWT can extract useful information that influences the daily streamflow from the raw predictors, and the water level has the most significant contribution to streamflow prediction. Accordingly, the XM-LSTM model can be viewed as a potentially useful approach for increasing the accuracy and explainability of streamflow forecasting.

Heterologous expression and enzymatic characteristics of sulfatase from Lactobacillus plantarum dy-1.

Barley, rich in bioactive components including dietary fiber, polyphenolic compounds and functional proteins, exhibits health benefits such as regulating glucose and lipid metabolism. Previous studies have found that the content and composition of free phenolic acids in barley may be significantly changed by fermentation with the laboratory patented strain Lactobacillus plantarum dy-1 (L. p dy-1), but the mechanism of enzymatic release of phenolic acid remains to be elucidated. Based on this, this study aimed to identify the key enzyme in L. p dy-1 responsible for releasing the bound phenolic acid and to further analyze its enzymatic properties. The Carbohydrate-Active enZYmes database revealed that L. p dy-1 encodes 7 types of auxiliary enzymes, among which we have identified a membrane sulfatase. The enzyme gene LPMS05445 was heterologous to that expressed in E. coli, and a recombinant strain was induced to produce the target protein and purified. The molecular weight of the purified enzyme was about 59.9 kDa, with 578.21 U mg-1 enzyme activity. The optimal temperature and pH for LPMS05445 expression were 40 °C and 7.0, respectively. Furthermore, enzymatic hydrolysis by LPMS05445 can obviously change the surface microstructure of dietary fiber from barley bran and enhance the release of bound phenolic acid, thereby increasing the free phenolic acid content and improving its physiological function. In conclusion, sulfatase produced by Lactobacillus plantarum dy-1 plays a key role in releasing bound phenolic acids during the fermentation of barley.

Single-port plus one in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux, a comparative analysis with short-term outcomes.

OBJECTIVE: To observe the safety and short-term outcomes of a new way of laparoscopic trocar placement in pediatric robotic-assisted Lich-Gregoir ureteral reimplantation for vesicoureteral reflux. METHODS: The retrospective study included 32 patients under 14 years diagnosed with primary vesicoureteral reflux (VUR). All these patients underwent robotic-assisted Lich-Gregoir ureteral reimplantation in our department from December 2020 to August 2022. These patients were divided into the following groups according to the different ways of trocar placement: 13 patients in group single-port plus one (SR) and 19 patients in group multiple-port (MR). Patients' characteristics as well as their perioperative and follow-up data were collected and evaluated. RESULTS: There was no significant difference in the data regarding patients' characteristics and preoperative data. These data included the grade of vesicoureteral reflux according to the voiding cystourethrogram (VCUG), and the differential degree of renal function (DRF) at the following time points: preoperative, postoperative, and comparison of preoperative and postoperative. There was no difference between the two groups. During surgery, the time of artificial pneumoperitoneum establishment, ureteral reimplantation time, and total operative time in the SR group were longer than those in the MR group. Yet only the time of artificial pneumoperitoneum establishment shows a statistical difference (P < 0.0001). Also, the peri-operative data, including the volume of blood loss, fasting time, hospitalization, and length of time that a ureteral catheter remained in place, and the number of postoperative complications demonstrate no difference. In addition, the SFU grade and VCUG grade at the following time point also show no difference between the two groups. CONCLUSION: The study demonstrates that SR in robotic-assisted Lich-Gregoir ureteral reimplantation has reached the same surgical effects as MR. In addition, the single-port plus one trocar placement receives a higher cosmetic satisfaction score from parents and did not increase the surgical time and complexity.

Effects evaluation of different exercises on subclinical left ventricular dysfunction in obese rats by speckle-tracking echocardiography.

OBJECTIVE: To identify subclinical left ventricle dysfunction (LVD) in obese rats by speckle-tracking echocardiography, and to evaluate the effects of 12-week Moderate-Intensity Continuous Training (MICT) or High-Intensity Interval Training (HIIT) on LV geometry, histology and function in obese rats. METHODS: Eighteen male standard or obese Sprague-Dawley rats were randomly divided into the Control group, the MICT group, and the HIIT group. Exercise interventions were conducted for 12 weeks, with equal total load and increased intensity gradient. Using dual-energy X-ray, two-dimensional speckle-tracking echocardiography, pulse Doppler, and HE staining to evalucate body shape, LV morphology, structure, and myocardial mechanics function. RESULTS: (1) Both MICT and HIIT have good weight loss shaping effect. (2) The LV of obese rats underwent pathological remodeling, with decreased longitudinal contractility and synchrony, and increased circumferential contractility and synchrony. (3) Exercise can inhibit LV pathological remodeling, improve myocardial mechanical function. HIIT is superior to MICT. (4) The global longitudinal strain of obese rats in the HIIT group showed a significant correlation with Fat% and Lean%. CONCLUSION: Obesity can induce LV pathological remodeling and subclinical dysfunction. Compared with MICT, 12-week HIIT can effectively inhibit the pathological remodeling of LV and promote the benign development of myocardial mechanical function in obese rats.

Predicting ambient PM2.5 concentrations via time series models in Anhui Province, China.

Due to rapid expansion in the global economy and industrialization, PM2.5 (particles smaller than 2.5 µm in aerodynamic diameter) pollution has become a key environmental issue. The public health and social development directly affected by high PM2.5 levels. In this paper, ambient PM2.5 concentrations along with meteorological data are forecasted using time series models, including random forest (RF), prophet forecasting model (PFM), and autoregressive integrated moving average (ARIMA) in Anhui province, China. The results indicate that the RF model outperformed the PFM and ARIMA in the prediction of PM2.5 concentrations, with cross-validation coefficients of determination R2, RMSE, and MAE values of 0.83, 10.39 µg/m3, and 6.83 µg/m3, respectively. PFM achieved the average results (R2 = 0.71, RMSE = 13.90 µg/m3, and MAE = 9.05 µg/m3), while the predicted results by ARIMA are comparatively poorer (R2 = 0.64, RMSE = 15.85 µg/m3, and MAE = 10.59 µg/m3) than RF and PFM. These findings reveal that the RF model is the most effective method for predicting PM2.5 and can be applied to other regions for new findings.

TGR5 signalling in heart and brain injuries: focus on metabolic and ischaemic mechanisms.

The heart and brain are the core organs of the circulation and central nervous system, respectively, and play an important role in maintaining normal physiological functions. Early neuronal and cardiac damage affects organ function. The relationship between the heart and brain is being continuously investigated. Evidence-based medicine has revealed the concept of the "heart- brain axis," which may provide new therapeutic strategies for certain diseases. Takeda protein-coupled receptor 5 (TGR5) is a metabolic regulator involved in energy homeostasis, bile acid homeostasis, and glucose and lipid metabolism. Inflammation is critical for the development and regeneration of the heart and brain during metabolic diseases. Herein, we discuss the role of TGR5 as a metabolic regulator of heart and brain development and injury to facilitate new therapeutic strategies for metabolic and ischemic diseases of the heart and brain.

The Anti-Inflammatory and Curative Exponent of Probiotics: A Comprehensive and Authentic Ingredient for the Sustained Functioning of Major Human Organs.

Several billion microorganisms reside in the gastrointestinal lumen, including viruses, bacteria, fungi, and yeast. Among them, probiotics were primarily used to cure digestive disorders such as intestinal infections and diarrhea; however, with a paradigm shift towards alleviating health through food, their importance is large. Moreover, recent studies have changed the perspective that probiotics prevent numerous ailments in the major organs. Probiotics primarily produce biologically active compounds targeting discommodious pathogens. This review demonstrates the implications of using probiotics from different genres to prevent and alleviate ailments in the primary human organs. The findings reveal that probiotics immediately activate anti-inflammatory mechanisms by producing anti-inflammatory cytokines such as interleukin (IL)-4, IL-10, IL-11, and IL-13, and hindering pro-inflammatory cytokines such as IL-1, IL-6, and TNF-α by involving regulatory T cells (Tregs) and T helper cells (Th cells). Several strains of Lactobacillus plantarum, Lactobacillus rhamnosus, Lactobacillus casei, Lactobacillus reuteri, Bifidobacterium longum, and Bifidobacterium breve have been listed among the probiotics that are excellent in alleviating various simple to complex ailments. Therefore, the importance of probiotics necessitates robust research to unveil the implications of probiotics, including the potency of strains, the optimal dosages, the combination of probiotics, their habitat in the host, the host response, and other pertinent factors.

Fabrication of nano-hammer shaped CuO@HApNWs for catalytic degradation of tetracycline.

With widespread and excessive use of antibiotics in medicine, poultry farming, and aquaculture, antibiotic residues have become a significant threat to both eco-environment and human health. In this paper, using hydroxyapatite nanowires (HApNWs) as an ecologically compatible carrier, a novel nano-hammer shaped conjunction with HApNW conjugating CuO microspheres (CuO@HApNWs) was successfully synthesized by in-situ agglomeration method. The catalytic degradation performance of the nano-hammer shaped CuO@HApNWs with Fenton-like activation was investigated by using tetracycline (TC) as a representative antibiotic pollutant. Remarkably, it exhibited excellent catalytic activity, which the removal rate of TC got to 92.0% within 40 min, and the pseudo-second-order reaction kinetic constant was 18.33 × 10-3 L mg-1·min-1, which was 26 times and 5 times than that of HApNWs and CuO, respectively. Furthermore, after recycling 6 times, the degradation efficiency of TC still remained above 85 %. Based on radical scavenger tests and electron paramagnetic resonance (EPR) spectroscopy, it demonstrated that the excellent activity of CuO@HApNWs was mainly attributed to the fact that Fenton-like activation promotes the circulation of Cu2+ and Cu+, the generated main active oxygen species (•OH and O2-•) achieve efficient degradation of TC. In summary, the nano-hammer shaped CuO@HApNWs could be in-situ synthesed, and used as an eco-friendly Fenton-like catalyst for effectively catalytic degradation of organic pollutants, which has great potential for wastewater treatment.

EGCG oxidation-derived polymers induce apoptosis in digestive tract cancer cells via regulating the renin-angiotensin system.

Green tea polyphenol (-)-Epigallocatechin-3-gallate (EGCG) has been well studied for its biological activities in the prevention of chronic diseases. However, the biological activities of EGCG oxidation-derived polymers remain unclear. Previously, we found that these polymers accumulated in intraperitoneal tissues after intraperitoneal injection and gained an advantage over native EGCG in increasing insulin sensitivity via regulating the renin-angiotensin system (RAS) in type 2 diabetic mice. The present study determined the pro-apoptosis activities and anticancer mechanisms of the EGCG oxidation-derived polymer preparation (the >10 kDa EGCG polymers) in digestive tract cancer cells. Upon incubation of the >10 kDa EGCG polymers with CaCo2 colon cancer cells, these polymers coated the cell surface and regulated multiple components of the RAS in favor of cancer inhibition, including the downregulation of angiotensin-converting enzyme (ACE), angiotensin-II (AngII) and AngII receptor type 1 (AT1R) in the pro-tumor axis, as well as the upregulation of angiotensin-converting enzyme 2 (ACE2) and angiotensin1-7 (Ang(1-7)) in the anti-tumor axis. The treatment also markedly increased angiotensinogen (AGT), which is the precursor of the angiotensin peptides. The regulation of these RAS components occurred prior to apoptosis. Similar pro-apoptotic mechanisms of the >10 kDa EGCG polymers, were also observed in TCA8113 oral cancer cells. The >10 kDa EGCG polymers exhibited compromised activities in scavenging or initiating reactive oxygen species compared to EGCG, but gained a higher reactivity toward sulfhydryl groups, including protein cysteine thiols. We propose that the polymers bind onto the cell surface and regulate multiple RAS components by reacting with the sulfhydryl groups on the ectodomains of transmembrane proteins.

Highly Adhesive and Self-Healing Zwitterionic Hydrogels as Antibacterial Coatings for Medical Devices.

Bacterial infection of medical devices has caused incalculable losses to maintenance costs and health care. A single coating with antibacterial function cannot guarantee the long-term use of the device, because the coating will be damaged and fall off during reuse. To solve this problem, the development of coatings with high adhesion and self-healing ability is a wise direction. In this paper, a multifunctional polyzwitterionic antibacterial hydrogel coating (PZG) composed of amphozwitterion monomer, anionic monomer, and quaternary ammonium cationic monomer was synthesized by dipping UV photoinitiated polymerization. The structure of PZGs was characterized by Fourier transform infrared spectroscopy, scanning electron microscopy, energy-dispersive X-ray spectroscopy, and X-ray photoelectron spectroscopy. Ascribing to the hydrogel internal electrostatic interaction, hydrogen bond, and cation-π interaction, the obtained PZGs exhibited high ductility (>1200% strain) and appropriate strength (>189 kPa). Remarkably, PZGs could also adhere firmly on different substrates through noncovalent interaction, and their adhesion could be controlled by adjusting the amount of zwitterionic. Reversible physical interactions in polymer networks endowed hydrogels with excellent self-healing properties. In addition, PZGs exhibit good antibacterial activity and biocompatibility due to the synergistic effect of quaternary ammonium cation and amphozwitterion monomer. This work provides a multifunctional antibacterial coating for medical equipment and has broad application prospects in the biomedical field.

Targeting gut microbiota in aging-related cardiovascular dysfunction: focus on the mechanisms.

The global population is aging and age-related cardiovascular disease is increasing. Even after controlling for cardiovascular risk factors, readmission and mortality rates remain high. In recent years, more and more in-depth studies have found that the composition of the gut microbiota and its metabolites, such as trimethylamine N-oxide (TMAO), bile acids (BAs), and short-chain fatty acids (SCFAs), affect the occurrence and development of age-related cardiovascular diseases through a variety of molecular pathways, providing a new target for therapy. In this review, we discuss the relationship between the gut microbiota and age-related cardiovascular diseases, and propose that the gut microbiota could be a new therapeutic target for preventing and treating cardiovascular diseases.

Effectiveness of acupuncture for pain relief in shoulder-hand syndrome after stroke: a systematic evaluation and Bayesian network meta-analysis.

Background: Shoulder-hand syndrome (SHS) is a common complication after stroke, and SHS-induced pain significantly hampers patients' overall recovery. As an alternative therapy for pain relief, acupuncture has certain advantages in alleviating pain caused by SHS after stroke. However, choosing the best treatment plan from a variety of acupuncture options is still a serious challenge in clinical practice. Therefore, we conducted this Bayesian network meta-analysis to comprehensively compare the effectiveness of various acupuncture treatment methods. Methods: We systematically searched for randomized controlled trials (RCTs) of acupuncture treatment in patients with post-stroke SHS published in PubMed, Embase, Cochrane, and Web of Science until 9 March 2023. We used the Cochrane bias risk assessment tool to assess the bias risk in the included original studies. Results: A total of 50 RCTs involving 3,999 subjects were included, comprising 19 types of effective acupuncture interventions. Compared to single rehabilitation training, the top three interventions for VAS improvement were floating needle [VAS = -2.54 (95% CI: -4.37 to -0.69)], rehabilitation + catgut embedding [VAS = -2.51 (95% CI: -4.33 to -0.68)], and other multi-needle acupuncture combinations [VAS = -2.32 (95% CI: -3.68 to -0.94)]. The top three interventions for improving the Fugl-Meyer score were eye acupuncture [Meyer = 15.73 (95% CI: 3.4627.95)], other multi-needle acupuncture combinations [Meyer = 12.22 (95% CI: 5.1919.34)], and traditional western medicine + acupuncture + traditional Chinese medicine [Meyer = 11.96 (95% CI: -0.59 to 24.63)]. Conclusion: Multiple acupuncture methods are significantly effective in improving pain and upper limb motor function in post-stroke SHS, with relatively few adverse events; thus, acupuncture can be promoted. Systematic Review Registration: https://www.crd.york.ac.uk/prospero/, CRD42023410957.

SBAS-InSAR Based Deformation Monitoring of Tailings Dam: The Case Study of the Dexing Copper Mine No.4 Tailings Dam.

The No.4 tailings pond of the Dexing Copper Mine is the second largest in Asia. The tailing pond is a dangerous source of man-made debris flow with high potential energy. In view of the lack of effective and low-cost global safety monitoring means in this region, in this paper, the time-series InSAR technology is innovatively introduced to monitor the deformation of tailings dam and significant key findings are obtained. First, the surface deformation information of the tailings pond and its surrounding areas was extracted by using SBAS-InSAR technology and Sentinel-1A data. Second, the cause of deformation is explored by analyzing the deformation rate, deformation accumulation, and three typical deformation rate profiles of the representative observation points on the dam body. Finally, the power function model is used to predict the typical deformation observation points. The results of this paper indicated that: (1) the surface deformation of the tailings dam can be categorized into two directions: the upper portion of the dam moving away from the satellite along the Line of Sight (LOS) at a rate of -40 mm/yr, whereas the bottom portion approaching the satellite along the LOS at a rate of 8 mm/yr; (2) the deformation of the dam body is mainly affected by the inventory deposits and the construction materials of the dam body; (3) according to the current trend, deformation of two typical observation points in the LOS direction will reach the cumulative deformation of 80 mm and -360 mm respectively. The research results can provide data support for safety management of No.4 tailings dam in the Dexing Copper Mine, and provide a method reference for monitoring other similar tailings dams.

Single-port-plus-one robot-assisted laparoscopic modified Lich-Gregoir direct nipple ureteral extravesical reimplantation in children with a primary obstructive megaureter.

Purpose: To introduce a new technique of single-port-plus-one robotic laparoscopic-modified Lich-Gregoir direct nipple ureteral extravesical reimplantation and ascertain its validity in the treatment of pediatric primary obstructive megaureter. Methods: Between January 2021 and November 2021, we retrospectively analyzed the clinical data of 12 children with primary obstructive megaureter who were admitted to the Department of Pediatric Surgery of Fujian Provincial Hospital. All 12 children were treated with single-port-plus-one robotic laparoscopic Lich-Gregoir direct nipple ureteral extravesical reimplantation. Five of them were female and seven were male, including nine cases were simple obstructive type, while the remaining three cases were obstructive with reflux type. The mean age of the children was 17.33 ± 6.99 (10-36) months and the mean follow-up time was 14.16 ± 1.75 (12-17) months. Changes in preoperative and first-year postoperative parameters were compared. Results: The mean operative time for all 12 children was 123.58 ± 10.85 (110-145) min, with a mean internal operative time of 101.42 ± 0.85 (90-120) min, a mean operative bleeding time of 2.42 ± 0.67 (2-4) ml, and a mean hematuria duration of 16.08 ± 1.44 (14-19) h. The mean indwelling catheterization time was 2.25 ± 0.45 (2-3) days and the mean hospitalization time was 3.83 ± 0.39 (3-4) days. At the postoperative first year, the ureteral diameter, calyceal diameter, and anterior-posterior renal pelvic diameter were found to be significantly smaller than at the preoperative period (18.83 ± 3.21 mm vs. 6.83 ± 1.27 mm, 13.99 ± 3.58 mm vs. 3.5 ± 2.90 mm, and 34.92 ± 4.25 mm vs. 10.08 ± 1.88 mm, P < 0.001). There was a significant increase in renal cortical thickness and the percentage of differential renal function (3.63 ± 1.66 mm vs. 5.67 ± 1.88 mm, 33.75 ± 2.77 mm vs. 37.50 ± 1.31 mm, P < 0.001). The resolution rate of obstruction was 100% and no child developed DeNovo vesicoureteral reflux. Conclusion: The technique of modified Lich-Gregoir direct nipple ureteral extravesical reimplantation can help maintain the physiological direction of the ureter and at the same time enhance the effectiveness of antirefluxing in robotic surgery. The design of a single-port-plus-one wound can produce a cosmetic appearance by concentrating and hiding the wound around the umbilicus. This modified reimplantation procedure has the potential to become a promising technique in the robot-assisted treatment of primary obstructive megaureter.

Chlorogenic acid as an indispensible partner of caffeic acid in coffee via selective regulation of prooxidative actions of caffeic acid.

Chlorogenic acid (CGA) and caffeic acid (CA) are two major phenolic acids in coffee. Though the International Agency for Research on Cancer has classified CA as a Group2B carcinogen, coffee consumption seems generally safe within the usual levels of intake and is more likely to benefit health than to harm it. We thus speculated that CGA may effectively suppress the carcinogenic potential of CA. In a molar ratio achievable in vivo, this study shows that CGA can inhibit (i) copper reduction caused by CA, (ii) CA oxidation caused by copper, (iii) the formation of hydroxyl radicals by CA and copper, and (iv) DNA damage induced by CA, quercetin or (-)-epigallocatechin-3-gallate in the presence of copper. CA tends to undergo autoxidation to produce hydrogen peroxide and quinone, which further reacts with proteins to form quinoproteins. This autoxidation at a tolerable level normally induces beneficial adaptive responses. This study shows that CGA is less efficient than CA in producing hydrogen peroxide and quinoprotein; however, together they synergistically produce hydrogen peroxide and quinoprotein in vitro at a molar ratio achievable in vivo. In conclusion, CGA can selectively regulate the prooxidant activities of CA depending on whether copper is involved or not. CGA could be viewed as an indispensable partner of CA in coffee, given its dual role in suppressing the carcinogenic potential of CA and boosting CA autoxidation which is beneficial for disease prevention.

Machine learning-based identification of CYBB and FCAR as potential neutrophil extracellular trap-related treatment targets in sepsis.

Objective: Sepsis related injury has gradually become the main cause of death in non-cardiac patients in intensive care units, but the underlying pathological and physiological mechanisms remain unclear. The Third International Consensus Definitions for Sepsis and Septic Shock (SEPSIS-3) definition emphasized organ dysfunction caused by infection. Neutrophil extracellular traps (NETs) can cause inflammation and have key roles in sepsis organ failure; however, the role of NETs-related genes in sepsis is unknown. Here, we sought to identify key NETs-related genes associate with sepsis. Methods: Datasets GSE65682 and GSE145227, including data from 770 patients with sepsis and 54 healthy controls, were downloaded from the GEO database and split into training and validation sets. Differentially expressed genes (DEGs) were identified and weighted gene co-expression network analysis (WGCNA) performed. A machine learning approach was applied to identify key genes, which were used to construct functional networks. Key genes associated with diagnosis and survival of sepsis were screened out. Finally, mouse and human blood samples were collected for RT-qPCR verification and flow cytometry analysis. Multiple organs injury, apoptosis and NETs expression were measured to evaluated effects of sulforaphane (SFN). Results: Analysis of the obtained DEGs and WGCNA screened a total of 3396 genes in 3 modules, and intersection of the results of both analyses with 69 NETs-related genes, screened out seven genes (S100A12, SLC22A4, FCAR, CYBB, PADI4, DNASE1, MMP9) using machine learning algorithms. Of these, CYBB and FCAR were independent predictors of poor survival in patients with sepsis. Administration of SFN significantly alleviated murine lung NETs expression and injury, accompanied by whole blood CYBB mRNA level. Conclusion: CYBB and FCAR may be reliable biomarkers of survival in patients with sepsis, as well as potential targets for sepsis treatment. SFN significantly alleviated NETs-related organs injury, suggesting the therapeutic potential by targeting CYBB in the future.

Construction of self-propelled micromotor for "hunting bacteria".

The inherent migration behavior of bacteria has inevitably impacted the advancement of the antibacterial treatment technology. Hunting bacteria, especially those with flagellates, requires self-propelled materials, which could kill bacteria autonomously. Herein, we designed and synthesized a self-propelled micromotor (SPM) tailed with poly(thiazole) to yield bimetallic organic frameworks (BiOFs), in which the assembly of BiOFs are similar to the "Newman projection". The moving speed of the obtained SPM was 238.6 µm s-1 and presented excellent antibacterial activity; more than 90% bacteria were hunted and killed in flowing water. Its minimum inhibitory concentration (MIC) against E. coli and S. aureus was 3.2 and 0.4 mg mL-1, respectively, and its antibacterial activity was still retained after recycling for 5 times. Its antibacterial mechanism along with the contribution of the active units and flow rate was investigated. In summary, a novel self-propelled material for hunting bacteria was synthesized by an unprecedented and efficient strategy. This approach is anticipated to create huge possibilities for its applications in the fields of antibacterial, disinfection, and microdevices.

Placental galectins: a subfamily of galectins lose the ability to bind ß-galactosides with new structural features†.

Galectins are a phylogenetically conserved family of soluble ß-galactoside binding proteins. There are 16 different of galectins, each with a specific function determined by its distinct distribution and spatial structure. Galectin-13, galectin-14, and galectin-16 are distinct from other galectin members in that they are primarily found in placental tissue. These galectins, also referred to as placental galectins, play critical roles in regulating pregnancy-associated processes, such as placenta formation and maternal immune tolerance to the embedded embryo. The unique structural characteristics and the inability to bind lactose of placental galectins have recently received significant attention. This review primarily examines the novel structural features of placental galectins, which distinguish them from the classic galectins. Furthermore, it explores the correlation between these structural features and the loss of ß-galactoside binding ability. In addition, the newly discovered functions of placental galectins in recent years are also summarized in our review. A detailed understanding of the roles of placental galectins may contribute to the discovery of new mechanisms causing numerous pregnancy diseases and enable the development of new diagnostic and therapeutic strategies for the treatment of these diseases, ultimately benefiting the health of mothers and offspring.