Cu/TiO2 adsorbents modified by air plasma for adsorption-oxidation of H2S.

In this study, non-thermal plasma (NTP) was employed to modify the Cu/TiO2 adsorbent to efficiently purify H2S in low-temperature and micro-oxygen environments. The effects of Cu loading amounts and atmospheres of NTP treatment on the adsorption-oxidation performance of the adsorbents were investigated. The NTP modification successfully boosted the H2S removal capacity to varying degrees, and the optimized adsorbent treated by air plasma (Cu/TiO2-Air) attained the best H2S breakthrough capacity of 113.29 mg H2S/gadsorbent, which was almost 5 times higher than that of the adsorbent without NTP modification. Further studies demonstrated that the superior performance of Cu/TiO2-Air was attributed to increased mesoporous volume, more exposure of active sites (CuO) and functional groups (amino groups and hydroxyl groups), enhanced Ti-O-Cu interaction, and the favorable ratio of active oxygen species. Additionally, the X-ray diffraction (XRD) and X-ray photoelectron spectroscopy (XPS) results indicated the main reason for the deactivation was the consumption of the active components (CuO) and the agglomeration of reaction products (CuS and SO42-) occupying the active sites on the surface and the inner pores of the adsorbents.

[Preparation of hybrid exosomes based on bovine milk exosomes and liposomes and pharmacodynamic study of sinomenine loaded exosomes in treatment of rheumatoid arthritis].

This study investigates the therapeutic effect of hybrid exosomes loaded with sinomenine(SIN) obtained by membrane fusion of milk exosomes with liposomes in collagen-induced arthritis(CIA) rats. Exosomes were isolated from fresh bovine milk by sucrose density gradient centrifugation, while liposomes were prepared using the emulsion solvent evaporation-low temperature curing method. Hybrid exosomes were characterized after membrane fusion through co-incubation: The morphology was detected by transmission electron microscopy, the particle size and potential by nanoparticle size potentiostat, and the expressions of surface characteristic proteins CD63 and TSG101 before and after fusion by Western blot(WB). The drug loading capacity and encapsulation rate of sinomenine were measured after the loading of sinomenine on exosomes by ultrasonic method. The CIA rat model was induced by collagen antibody. The efficacy experiment consisted of the control group, model group, SIN group, SIN-liposome group, SIN-milk exosome group, SIN-hybrid exosome group and positive drug(dexamethasone) group. The changes in body mass of rats during administration were recorded. Besides, the foot swelling, immune organ index, arthritis index, microcirculation index, synovial histopathology, and serum inflammatory factor levels detected by enzyme-linked immunosorbent assay were observed for pharmacodynamical study. Under transmission electron microscopy, both hybrid exosomes and milk exosomes showed saucer-like appearance. After co-incubation, the exosome particle size increased from(97.92±3.42)nm to(132.70±4.07)nm, and the Zeta potential changed from(-2.01±0.33)mV to(-17.90±2.13)mV. WB assay showed that CD63 and TSG101 proteins were normally expressed in milk exosomes and hybrid exosomes. The encapsulation rate of milk exosomes was 31.64%±2.48%, with a drug loading of 2.35%±0.52%, while the hybrid exosomes exhibited an encapsulation rate of 48.21%±3.12% and drug loading of 3.17%±0.36%, as determined by the microplate reader. Pharmacodynamic results showed that compared with the model group, the general condition, swelling degree of foot, arthritis index and immune organ index of all drug administration groups were significantly improved(P<0.05, P<0.01); microvascular comprehensive score and vascular resistance were significantly decreased(P<0.05, P<0.01); serum levels of TNF-α, IL-1ß and IL-6 inflammatory factors were significantly decreased(P<0.01); and the lesions of synovial tissue were improved to some extent. Meanwhile, compared with the SIN group, SIN-liposome group and SIN-milk exosome group, the SIN-hybrid exosome group had a more stable and durable drug effect. The hybrid exosomes obtained by co-incubation of milk-derived exosomes with liposomes successfully improved the drug carrying capacity of exosomes and biocompatibility of liposomes. The hybrid exosomes loaded with sinomenine have good efficacy on CIA model rats, and can effectively solve the problems of TCM such as sinomenine, which have good efficacy but short biological half-life. The study provides new insights for the development of TCM and the treatment of diseases such as rheumatoid arthritis.

Integration of Transcriptomics and Metabolomics Reveals the Antitumor Mechanism of Protopanaxadiol Triphenylphosphate Derivative in Non-Small-Cell Lung Cancer.

The objective of this study was to enhance the membrane permeability and anticancer effectiveness of (20S)-protopanaxadiol (PPD) by introducing triphenylphosphonium into the OH group at the C-3 site. This study shows that the anti-proliferation activity of CTPPPPD, with an IC50 value of 1.65 ± 0.10 µmol/L, was 33-times better than that of PPD (with an IC50 value of 54.56 ± 4.56 µmol/L) and superior to that of cisplatin (with an IC50 value of 1.82 ± 0.25 µmol/L) against A549 cells. Biological examinations suggested that CTPPPPD treatment reduced the growth rate of A549 cells, increased the permeability of cell membranes, and changed the structure of chromosomal DNA in a concentration-dependent manner. Annexin V/PI assay and flow cytometry were employed to detect the effect of CTPPPPD on the apoptosis of A549 cells. The results showed that CTPPPPD could induce the apoptosis of A549 cells, and the apoptosis rate of A549 cells treated with 0, 1.0, 2.0, and 4.0 µM of CTPPPPD for 24 h was 0%, 4.9%, 12.7%, and 31.0%, respectively. The integration of transcriptomics and metabolomics provided a systematic and detailed perspective on the induced antitumor mechanisms. A combined analysis of DEGs and DAMs suggested that they were primarily involved in the central carbon metabolism pathway in cancer, as well as the metabolism of aminoacyl-tRNA biosynthesis, alanine, aspartate, and glutamate. Central carbon metabolism in cancer-related genes, i.e., SLC16A3, FGFR3, LDHA, PGAM1, and SLC2A1, significantly reduced after treatment with CTPPPPD. In particular, the dominant mechanism responsible for total antitumor activity may be attributed to perturbations in the PI3K-AKT, MAPK, and P53 pathways. The findings derived from transcriptomics and metabolomics were empirically confirmed through q-PCR and molecular docking. Further analyses revealed that CTPPPPD could be a promising lead for the development of protopanaxadiol for non-small-cell lung cancer (NSCLC) drugs.

Influence of lipid oxidation on the digestive efficiency of Antarctic krill oil: insights from a simulated gastrointestinal digestion model.

Lipid oxidation profoundly impacts its digestibility, a topic that has been predominantly investigated in triglyceride (TAG)-based dietary lipids. However, there is a dearth of similar research on lipids with diverse classes, such as Antarctic krill oil (AKO), which encompasses a spectrum of lipids including glycerides and phospholipids. This study aimed to elucidate the influence of lipid oxidation on the digestibility of AKO through a simulated gastrointestinal digestion (SGID) model. Post-SGID, AKO exhibited oxidative changes, evidenced by an escalation in peroxide value, conjugated diene value, thiobarbituric acid reactive substances and Schiff base formation. Concurrently, the digestibility of oxidized AKO was found to be inferior to that of fresh AKO, as indicated by a diminished hydrolysis degree of TAGs and phosphatidylcholine (PC), along with a reduced release of free fatty acids. Furthermore, co-digestion with tea polyphenol palmitate was observed to mitigate the oxidation of AKO and the digestion of PC during the SGID, while exerting no significant impact on TAG digestion. Notably, the emulsification capacity of oxidized AKO in a simulated intestinal fluid (without pancreatin and phospholipase A2) was also found to be inferior to that of its fresh counterpart. These findings suggest that lipid oxidation may adversely affect the emulsification capacity of AKO under simulated intestinal conditions, thereby leading to a decrement in digestibility.

Occupational Exposure to Silica Dust and Silicosis Risk in Chinese Noncoal Mines: Qualitative and Quantitative Risk Assessment.

BACKGROUND: Despite increasing awareness, silica dust-induced silicosis still contributes to the huge disease burden in China. Worryingly, recent silica dust exposure levels and silicosis risk in Chinese noncoal mines remain unclear. OBJECTIVE: We aimed to determine recent silica dust exposure levels and assess the risk of silicosis in Chinese noncoal mines. METHODS: Between May and December 2020, we conducted a retrospective cohort study on 3 noncoal mines and 1 public hospital to establish, using multivariable Cox regression analyses, prediction formulas of the silicosis cumulative hazard ratio (H) and incidence (I) and a cross-sectional study on 155 noncoal mines in 10 Chinese provinces to determine the prevalence of silica dust exposure (PDE), free silica content, and total dust and respirable dust concentrations. The qualitative risk of silicosis was assessed using the International Mining and Metals Commission's risk-rating table and the occupational hazard risk index; the quantitative risk was assessed using prediction formulas. RESULTS: Kaplan-Meier survival analysis revealed significant differences in the silicosis probability between silica dust-exposed male and female miners (log-rank test χ21=7.52, P=.01). A total of 126 noncoal mines, with 29,835 miners and 4623 dust samples, were included; 13,037 (43.7%) miners were exposed to silica dust, of which 12,952 (99.3%) were male. The median PDE, free silica content, total dust concentration, and respirable dust concentration were 61.6%, 27.6%, 1.30 mg/m3, and 0.58 mg/m3, respectively, indicating that miners in nonmetal, nonferrous metal, small, and open-pit mines suffer high-level exposure to silica dust. Comprehensive qualitative risk assessment showed noncoal miners had a medium risk of silicosis, and the risks caused by total silica dust and respirable silica dust exposure were high and medium, respectively. When predicting H and I over the next 10, 20, and 30 years, we assumed that the miner gender was male. Under exposure to current total silica dust concentrations, median I10, I20, and I30 would be 6.8%, 25.1%, and 49.9%, respectively. Under exposure to current respirable silica dust concentrations, median I10, I20, and I30 would be 6.8%, 27.7%, and 57.4%, respectively. These findings showed that miners in nonmetal, nonferrous metal, small, and open-pit mines have a higher I and higher qualitative silicosis risk. CONCLUSIONS: Chinese noncoal miners, especially those in nonmetal, nonferrous metal, small, and open-pit mines, still suffer high-level exposure to silica dust and a medium-level risk of silicosis. Data of both total silica dust and respirable silica dust are vital for occupational health risk assessment in order to devise effective control measures to reduce noncoal mine silica dust levels, improve miners' working environment, and reduce the risk of silicosis.

Pairing Oxygen Reduction and Water Oxidation for Dual-pathway H2O2 Production.

Hydrogen peroxide (H2O2) is a crucial chemical applied in various industry sectors. However, the current industrial anthraquinone process for H2O2 synthesis is carbon-intensive. With sunlight and renewable electricity as energy inputs, photocatalysis and electrocatalysis have great potential for green H2O2 production from oxygen (O2) and water (H2O). Herein, we review the advances in pairing two-electron O2 reduction and two-electron H2O oxidation reactions for dual-pathway H2O2 synthesis. The basic principles, paired redox reactions, and catalytic device configurations are introduced initially. Aligning with the energy input, the latest photocatalysts, electrocatalysts, and photo-electrocatalysts for dual-pathway H2O2 production are discussed afterward. Finally, we outlook the research opportunities in the future. This minireview aims to provide insights and guidelines for the broad community who are interested in catalyst design and innovative technology for on-site H2O2 synthesis.

Effects of integrated traditional Chinese and Western medicine for acute pancreatitis: A real-world study in a tertiary teaching hospital.

AIM: This study aimed to evaluate whether integrated traditional Chinese medicine (TCM) and Western medicine (WM) is more effective than WM for acute pancreatitis (AP). METHODS: Patients with AP were enrolled and divided into the TCM and WM (TCM&WM) and WM groups according to the therapeutic protocol in real clinical settings. We applied 1:3 propensity score matching, which was to adjust confounding factors. The primary outcome was mortality, whereas the secondary outcomes were organ failure, organ supportive therapies, local complications, hospitalization cost, and length of hospital stay. Sensitivity and subgroup analyses were also performed. RESULTS: Of 5442 patients with AP, 4691 and 751 were included in the TCM&WM and WM groups, respectively. After PSM, patient baseline characteristics were well balanced. Compared with the WM group (n = 734), the TCM&WM group (n = 2096) had lower overall mortality rate (1.7% vs. 3.4%; risk ratio, 0.482; 95% confidence interval, 0.286-0.810; p = 0.005). The TCM&WM group was associated with lower risk of persistent renal failure, multiple organ failure, and infection, lower utilization of organ supportive therapies, shortened lengths of hospital and intensive care unit stay, and lower hospital costs. Sensitivity analyses showed similar results. Subgroup analysis favored TCM&WM treatment for patients aged < 60 years, with hypertriglyceridic etiology, and with admission interval between 24 and 48 h. CONCLUSION: TCM&WM treatment can achieve lower risks of mortality and organ failure and better economic effectiveness in patients with AP than WM treatment. This study provides a promising alternative of TCM&WM treatment for AP in the real-world setting.

Developing a Framework for Industrial Noise Risk Management Based on Noise Kurtosis and Its Adjustment.

OBJECTIVES: Noise risk control or management based on noise level has been documented, but noise risk management based on a combination of noise level and noise's temporal structure is rarely reported. This study aimed to develop a framework for industrial noise risk management based on noise kurtosis (reflecting noise's temporal structure) and its adjustment for the noise level. DESIGN: A total of 2805 Chinese manufacturing workers were investigated using a cross-sectional survey. The noise exposure data of each subject included LEX,8h, cumulative noise exposure (CNE), kurtosis, and kurtosis-adjusted LEX,8h (LEX,8h-K). Noise-induced permanent threshold shifts were estimated at 3, 4, and 6 kHz frequencies (NIPTS346) and 1, 2, 3, and 4 kHz frequencies (NIPTS1234). The prevalence of high-frequency noise-induced hearing loss prevalence (HFNIHL%) and noise-induced hearing impairment (NIHI%) were determined. Risk346 or Risk1234 was predicted using the ISO 1999 or NIOSH 1998 model. A noise risk management framework based on kurtosis and its adjustment was developed. RESULTS: Kurtosis could identify the noise type; Kurtosis combining noise levels could identify the homogeneous noise exposure group (HNEG) among workers. Noise kurtosis was a risk factor of HFNIHL or NIHI with an adjusted odds ratio of 1.57 or 1.52 (p < 0.01). At a similar CNE level, the NIPTS346, HFNIHL%, NIPTS1234, or NIHI% increased with increasing kurtosis. A nonlinear regression equation (expressed by logistic function) could rebuild a reliable dose-effect relationship between LEX,8h-K and NIPTS346 at the 70 to 95 dB(A) noise level range. After the kurtosis adjustment, the median LEX,8h was increased by 5.45 dB(A); the predicted Risk346 and Risk1234 were increased by 11.2 and 9.5%, respectively; NIPTS346-K of complex noise at exposure level <80, 80 to 85, and 85 to 90 dB(A), determined from the nonlinear regression equation, was almost the same as the Gaussian noise. Risk management measures could be recommended based on the exposure risk rating or the kurtosis-adjusted action levels (e.g., the lower and upper action levels were 80 and 85 dB(A), respectively). CONCLUSIONS: The kurtosis and its adjustment for noise levels can be used to develop an occupational health risk management framework for industrial noise. More human studies are needed to verify the risk management framework.

Ontology of clinical practice guidelines for Integrated Traditional Chinese and Western Medicine.

OBJECTIVE: Clinical practice guidelines (CPGs) for Integrated Traditional Chinese and Western Medicine (TCM and WM) are important medical documents used to assist medical decision-making and are of great significance for standardizing clinical pathways. However, due to the constraints of text format, it is difficult for Integrated TCM and WM CPGs to play a real role in medical practice. In addition, how to standardize the structure and semantic relationships between Integrated TCM and WM CPG knowledge, and realize the construction of computable, sharable and reliable CPGs, remains an urgent issue to be addressed. Therefore, we are proposing an ontology of CPGs for Integrated TCM and WM. METHODS: We first initialized domain concepts and relationships to ensure the accuracy of the ontology knowledge structure. We then screened CPGs that meet the standards for Integrated TCM and WM, analyzed and classified the contents, and extracted the common structures. Based on the seven-step ontology construction method combined with inference-complement, referring to the representation methods and hierarchical relationships of terms and concepts in MeSH, ICD-10, SNOMED-CT, and other ontologies and terminology sets, we formed the concept structure and semantic relationship tables for the ontology. We also achieved the matching and mapping between the ontology and reference ontologies and term sets. Next, we defined the aspects and constraints of properties, selected multiple Integrated TCM and WM CPGs as instances to populate, and used ontology reasoning tools and formulated defined inference rules to reason and extend the ontology. Finally, we evaluated the performance of the ontology. RESULTS: The content of the Integrated TCM and WM CPGs is divided into nine parts: basic information, background, development method, clinical question, recommendation, evidence, conclusion, result, and reason for recommendations. The Integrated TCM and WM CPG ontology has 152 classes and defines 90 object properties and 114 data properties, with a maximum classification depth of 4 layers. The terms of disease, drug and examination item names in the ontology have been standardized. CONCLUSIONS: This study proposes an Integrated TCM and WM CPG ontology. The ontology adopts a modular design, which has both sharing and scaling ability, and can express rich guideline knowledge. It provides important support for the semantic processing and computational application of guideline documents.

Assessing levelized cost of electric vehicle recharging in China.

Electric vehicle (EV) purchasing decisions are significantly influenced by costs. Focusing on China, this research comprehensively examines the levelized costs of EV recharging (including charging and swapping) at the provincial level considering various factors, including charging locations, time of charging, and power levels. Results indicate that the national average EV charging costs, with and without home chargers, amount to 0.973 RMB/kWh and 1.148 RMB/kWh, respectively. Remarkable variations are observed among provinces, with Xinjiang and Shanghai experiencing the lowest and highest levelized cost of EV charging (LCOC), respectively, with disparities of up to 147.26%, primarily attributed to regional discrepancies in electricity prices and vehicle usage intensity. Despite generous capital subsidies, swapping costs remain considerably higher than charging, ranging from 3.780 RMB/kWh to 4.082 RMB/kWh. Additionally, the sensitivity analysis of major parameters, including infrastructure utilization, suggests that levelized EV recharging costs are already more cost-attractive than the fuel costs of comparable gasoline cars at today's utilization rates.

Diversity and Activity of Soil N2O-Reducing Bacteria Shaped by Urbanization.

Nitrous oxide (N2O) is a potent greenhouse gas with various production pathways. N2O reductase (N2OR) is the primary N2O sink, but the distribution of its gene clades, typically nosZI and atypically nosZII, along urbanization gradients remains poorly understood. Here we sampled soils from forests, parks, and farmland across eight provinces in eastern China, using high-throughput sequencing to distinguish between two N2O-reducing bacteria clades. A deterministic process mainly determined assemblies of the nosZI communities. Homogeneous selection drove nosZI deterministic processes, and both homogeneous and heterogeneous selection influenced nosZII. This suggests nosZII is more sensitive to environmental changes than nosZI, with significant changes in community structure over time or space. Ecosystems with stronger anthropogenic disturbance, such as urban areas, provide diverse ecological niches for N2O-reducing bacteria (especially nosZII) to adapt to environmental fluctuations. Structural equation modeling (SEM) and correlation analyses revealed that pH significantly influences the community composition of both N2O-reducing bacteria clades. This study underscores urbanization's impact on N2O-reducing bacteria in urban soils, highlighting the importance of nosZII and survival strategies. It offers novel insights into the role of atypical denitrifiers among N2O-reducing bacteria, underscoring their potential ecological importance in mitigating N2O emissions from urban soils.

Fecal microbiota transplantation as a new way for OVA-induced atopic dermatitis of juvenile mice.

Children all over the world suffer from atopic dermatitis (AD), a prevalent condition that impairs their health. Corticosteroids, which have long-term negative effects, are frequently used to treat AD. There has been a growing body of research on the gut microbiota's function in AD. Nevertheless, the function and underlying mechanisms of fecal microbiota transplantation (FMT) in AD children remain to be established. Therefore, in order to assess the preventive effects of FMT treatment on AD and investigate the mechanisms, we constructed an ovalbumin (OVA)-induced juvenile mouse AD model in this investigation. This study explored the role and mechanism of FMT treatment in AD through 16S RNA sequencing, pathological histological staining, molecular biology, and Flow cytometry. Results demonstrated that the FMT treatment improved the gut microbiota's diversity and composition, bringing it back to a level similar to that of a close donor. Following FMT treatment, OVA-specific antibodies were inhibited, immunoglobulin (Ig) E production was decreased, the quantity of mast cells and eosinophils was decreased, and specific inflammatory markers in the skin and serum were decreased. Further mechanistic studies revealed that FMT treatment induced CD103+ DCs and programmed cell death ligand 1 (PD-L1)/programmed cell death 1 (PD-1) expression in skin-draining lymph nodes and promoted Treg production to induce immune tolerance and suppress skin inflammation. Meanwhile, changes in the gut microbiota were substantially correlated with Th2 cytokines, OVA-specific antibodies, and PD-L1/PD-1. In conclusion, FMT regulates the Th1/Th2 immunological balance and the gut microbiota. It may also inhibit AD-induced allergy responses through the PD-L1/PD-1 pathway, and providing a unique idea and possibly a fresh approach to the treatment of AD.

Chaiqin chengqi decoction treatment mitigates hypertriglyceridemia-associated acute pancreatitis by modulating liver-mediated glycerophospholipid metabolism.

BACKGROUND: The incidence of hypertriglyceridemia-associated acute pancreatitis (HTG-AP) is increasing globally and more so in China. The characteristics of liver-mediated metabolites and related key enzymes are rarely reported in HTG-AP. Chaiqin chengqi decoction (CQCQD) has been shown to protect against AP including HTG-AP in both patients and rodent models, but the underlying mechanisms in HTG-AP remain unexplored. PURPOSE: To assess the characteristics of liver-mediated metabolism and the therapeutic mechanisms of CQCQD in HTG-AP. METHODS: Male human apolipoprotein C3 transgenic (hApoC3-Tg; leading to HTG) mice or wild-type littermates received 7 intraperitoneal injections of cerulein (100 µg/kg) to establish HTG-AP and CER-AP, respectively. In HTG-AP, some mice received CQCQD (5.5 g/kg) gavage at 1, 5 or 9 h after disease induction. AP severity and related liver injury were determined by serological and histological parameters; and underlying mechanisms were identified by lipidomics and molecular biology. Molecular docking was used to identify key interactions between CQCQD compounds and metabolic enzymes, and subsequently validated in vitro in hepatocytes. RESULTS: HTG-AP was associated with increased disease severity indices including augmented liver injury compared to CER-AP. CQCQD treatment reduced severity and liver injury of HTG-AP. Glycerophospholipid (GPL) metabolism was the most disturbed pathway in HTG-AP in comparison to HTG alone. In HTG-AP, the mRNA level of GPL enzymes involved in phosphocholine (PC) and phosphatidylethanolamine (PE) synthesis (Pcyt1a, Pcyt2, Pemt, and Lpcat) were markedly upregulated in the liver. Of the GPL metabolites, lysophosphatidylethanolamine LPE(16:0) in serum of HTG-AP was significantly elevated and positively correlated with the pancreas histopathology score (r = 0.65). In vitro, supernatant from Pcyt2-overexpressing hepatocytes co-incubated with LPE(16:0) or phospholipase A2 (a PC- and PE-hydrolyzing enzyme) alone induced pancreatic acinar cell death. CQCQD treatment downregulated PCYT1a and PCYT2 enzyme levels in the liver. Hesperidin and narirutin were identified top two CQCQD compounds with highest affinity docking to PCYT1a and PCYT2. Both hesperidin and narirutin reduced the level of some GPL metabolites in hepatocytes. CONCLUSION: Liver-mediated GPL metabolism is excessively activated in HTG-AP with serum LPE(16:0) level correlating with disease severity. CQCQD reduces HTG-AP severity partially via modulating key enzymes in GPL metabolism pathway.

Terrestrial invertebrate hosts of human pathogens in urban ecosystems.

Terrestrial invertebrates in urban ecosystems are extremely species-rich, have many important roles in material flow and energy circulation, and are host to many human pathogens that pose threats to human health. These invertebrates are widely distributed in urban areas, including both out- and in-door environments. Consequently, humans are frequently in contact with them, which provides many opportunities for them to pose human health risks. However, comprehensive knowledge on human pathogen transfer via invertebrates is lacking, with research to date primarily focused on dipterans (e.g., mosquitoes, flies). Here, we take a broad taxonomic approach and review terrestrial invertebrate hosts (incl. mosquitoes, flies, termites, cockroaches, mites, ticks, earthworms, collembola, fleas, snails, and beetles) of human pathogens, with a focus on transmission pathways. We also discuss how urbanization and global warming are likely to influence the communities of invertebrate hosts and have flow-on risks to human health. Finally, we identify current research gaps and provide perspectives on future directions.

Elevated meteorin-like protein from high-intensity interval training improves heart function via AMPK/HDAC4 pathway.

High-intensity interval training (HIIT) has been found to be more effective in relieving heart failure (HF) symptoms, than moderate-intensity continuous aerobic training (MICT). Additionally, higher meteorin-like protein (Metrnl) levels are seen after HIIT versus MICT. We investigated whether Metrnl contributed to post-HF cardiac functional improvements, and the signaling pathways involved. 50 HF patients underwent MICT, and another 50, HIIT, which was followed by cardiac function and serum Metrnl measurements. Metrnl was also measured in both blood and skeletal muscle samples of mice with transverse aortic constriction-induced HF after undergoing HIIT. Afterward, shRNA-containing adenovectors were injected into mice, yielding five groups: control, HF, HF + HIIT + scrambled shRNA, HF + HIIT + shMetrnl, and HF + Metrnl (HF + exogenous Metrnl). Mass spectrometry identified specific signaling pathways associated with increased Metrnl, which was confirmed with biochemical analyses. Glucose metabolism and mitochondrial functioning were evaluated in cardiomyocytes from the five groups. Both HF patients and mice had higher circulating Metrnl levels post-HIIT. Metrnl activated AMPK in cardiomyocytes, subsequently increasing histone deacetylase 4 (HDAC4) phosphorylation, leading to its cytosolic sequestration and inactivation via binding with chaperone protein 14-3-3. HDAC4 inactivation removed its repression on glucose transporter type 4, which, along with increased mitochondrial complex I-V expression, yielded improved aerobic glucose respiration and alleviation of mitochondrial dysfunction. All these changes ultimately result in improved post-HF cardiac functioning. HIIT increased skeletal muscle Metrnl production, which then operated on HF hearts to alleviate their functional defects, via increasing aerobic glucose metabolism through AMPK-HDAC4 signaling.

The tumor suppressor Parkin exerts anticancer effects through regulating mitochondrial GAPDH activity.

Cancer cells preferentially utilize glycolysis for energy production, and GAPDH is a critical enzyme in glycolysis. Parkin is a tumor suppressor and a key protein involved in mitophagy regulation. However, the tumor suppression mechanism of Parkin has still not been elucidated. In this study, we identified mitochondrial GAPDH as a new substrate of the E3 ubiquitin ligase Parkin, which mediated GAPDH ubiquitination in human cervical cancer. The translocation of GAPDH into mitochondria was driven by the PINK1 kinase, and either PINK1 or GAPDH mutation prevented the accumulation of GAPDH in mitochondria. Parkin caused the ubiquitination of GAPDH at multiple sites (K186, K215, and K219) located within the enzyme-catalyzed binding domain of the GAPDH protein. GAPDH ubiquitination was required for mitophagy, and stimulation of mitophagy suppressed cervical cancer cell growth, indicating that mitophagy serves as a type of cell death. Mechanistically, PHB2 served as a key mediator in GAPDH ubiquitination-induced mitophagy through stabilizing PINK1 protein and GAPDH mutation resulted in the reduced distribution of PHB2 in mitophagic vacuole. In addition, ubiquitination of GAPDH decreased its phosphorylation level and enzyme activity and inhibited the glycolytic pathway in cervical cancer cells. The results of in vivo experiments also showed that the GAPDH mutation increased glycolysis in cervical cancer cells and accelerated tumorigenesis. Thus, we concluded that Parkin may exert its anticancer function by ubiquitinating GAPDH in mitochondria. Taken together, our study further clarified the molecular mechanism of tumor suppression by Parkin through the regulation of energy metabolism, which provides an experimental basis for the development of new drugs for the treatment of human cervical cancer.

A Live-Cell Epigenome Manipulation by Photo-Stimuli-Responsive Histone Methyltransferase Inhibitor.

Post-translational modifications on the histone H3 tail regulate chromatin structure, impact epigenetics, and hence the gene expressions. Current chemical modulation tools, such as unnatural amino acid incorporation, protein splicing, and sortase-based editing, have allowed for the modification of histones with various PTMs in cellular contexts, but are not applicable for editing native chromatin. The use of small organic molecules to manipulate histone-modifying enzymes alters endogenous histone PTMs but lacks precise temporal and spatial control. To date, there has been no achievement in modulating histone methylation in living cells with spatiotemporal resolution. In this study, a new method is presented for temporally manipulating histone dimethylation H3K9me2 using a photo-responsive inhibitor that specifically targets the methyltransferase G9a on demand. The photo-caged molecule is stable under physiological conditions and cellular environments, but rapidly activated upon exposure to light, releasing the bioactive component that can immediately inhibit the catalytic ability of the G9a in vitro. Besides, this masked compound could also efficiently reactivate the inhibition of methyltransferase activity in living cells, subsequently suppress H3K9me2, a mark that regulates various chromatin functions. Therefore, the chemical system will be a valuable tool for manipulating the epigenome for therapeutic purposes and furthering the understanding of epigenetic mechanisms.

WeedCube: Proximal hyperspectral image dataset of crops and weeds for machine learning applications.

WeedCube dataset consists of hyperspectral images of three crops (canola, soybean, and sugarbeet) and four invasive weeds species (kochia, common waterhemp, redroot pigweed, and common ragweed). Plants were grown in two separate greenhouses and plant canopies were captured from a top-down camera angle. A push-broom hyperspectral sensor in the visible near infrared region of 400-1000 nm was used for data collection. The dataset includes 160 calibrated images. The number of images can be further increased by selection of smaller region of interests (ROIs). Dataset is supplemented by Jupyter Notebook scripts that help in data augmentation, spectral pre-processing, ROI selection for points and images, and data visualization. The primary purpose of this dataset is to support weed classification or identification studies by enhancing existing training datasets and validating the generalization capabilities of existing models. Owing to the three-dimensional (3D) nature of hyperspectral images, this dataset can also be utilized by researchers and educators across various domains for the development and testing of deep learning algorithms, the creation of automated data processing pipelines effective for 3D data, the development of tools for 3D data visualization, the creation of innovative solutions for data compression, and addressing system memory issues associated with high-dimensional data.

Mitochondria at the Crossroads of Cholestatic Liver Injury: Targeting Novel Therapeutic Avenues.

Bile acids are byproducts of cholesterol metabolism in the liver and constitute the primary components of bile. Disruption of bile flow leads to cholestasis, characterized by the accumulation of hydrophobic bile acids in the liver and bloodstream. Such accumulation can exacerbate liver impairment. This review discussed recent developments in understanding how bile acids contribute to liver damage, including disturbances in mitochondrial function, endoplasmic reticulum stress, inflammation, and autophagy dysfunction. Mitochondria play a pivotal role in cholestatic liver injury by influencing hepatocyte apoptosis and inflammation. Recent findings linking bile acids to liver damage highlight new potential treatment targets for cholestatic liver injury.