Blockage of MLKL prevents myelin damage in experimental diabetic neuropathy.

SignificanceDiabetic neuropathy is a commonly occurring complication of diabetes that affects hundreds of millions of patients worldwide. Patients suffering from diabetic neuropathy experience abnormal sensations and have damage in their peripheral nerve axons as well as myelin, a tightly packed Schwann cell sheath that wraps around axons to provide insulation and increases electrical conductivity along the nerve fibers. The molecular events underlying myelin damage in diabetic neuropathy are largely unknown, and there is no efficacious treatment for the disease. The current study, using a diabetic mouse model and human patient nerve samples, uncovered a molecular mechanism underlying myelin sheath damage in diabetic neuropathy and provides a potential treatment strategy for the disease.

Direct visualization endoscopic retrograde appendicitis therapy for treatment of acute uncomplicated appendicitis.

OBJECTIVE: To investigate the diagnostic and therapeutic value of direct visualization (single-use eyeMax subscope) endoscopic management of acute uncomplicated appendicitis. METHODS: Thirty-six patients diagnosed with acute uncomplicated appendicitis, confirmed by computed tomography or ultrasonography, from Jan 2023 to Feb 2024 were enrolled in this study. We collected demographics, colonoscopy findings, subscope findings, clinical outcomes of endoscopic retrograde appendicitis therapy (ERAT), and adverse events associated with ERAT. RESULTS: Appendiceal intubation was successful for all 36 patients. Thirty-five patients (97.2%) were definitely confirmed as having acute uncomplicated appendicitis. One patient with negative appendicitis was diagnosed as having cecal diverticulitis with fecalith incarceration. The mean procedure time was 13.1 ± 13.6 min. One patient presented with worsening abdominal pain, and a computed tomography scan suggested a perforated appendix. The mean length of hospitalizations was 1.78 ± 2 days. The mean follow-up was 158 days; during this period, two patients (5.6%) experienced recurrent abdominal pain after 23 and 88 days and subsequently underwent laparoscopic appendectomy. CONCLUSION: Direct visualization ERAT may be effective for diagnosing and treating acute uncomplicated appendicitis and seems to have a low complication rate.

Heralded quantum multiplexing entanglement between stationary qubits via distribution of high-dimensional optical entanglement.

Quantum entanglement between pairs of remote quantum memories (QMs) is a prerequisite for realizing many applications in quantum networks. Here, we present a heralded protocol for the parallel creation of quantum entanglement among multiple pairs of QMs placed in spatially separated nodes, where each QM, encoding a stationary qubit, couples to an optical cavity and deterministically interacts with single photons. Our protocol utilizes an entangled photon pair encoded in the high-dimensional time-bin degree of freedom to simultaneously entangle multiple QM pairs, and is efficient in terms of reducing the time consumption and photon loss during transmission. Furthermore, our approach can be extended to simultaneously support spatial-temporal multiplexing, as its success is heralded by the detection of single photons. These distinguishing features make our protocol particularly useful for long-distance quantum communication and large-scale quantum networks.

Rotating Single-Antenna Spoofing Signal Detection Method Based on IPNN.

The traditional carrier-phase differential detection technology mainly relies on the spatial processing method, which uses antenna arrays or moving antennas to detect spoofing signals, but it cannot be applied to static single-antenna receivers. Aiming at this problem, this paper proposes a rotating single-antenna spoofing signal detection method based on the improved probabilistic neural network (IPNN). When the receiver antenna rotates at a constant speed, the carrier-phase double difference of the real signal will change with the incident angle of the satellite. According to this feature, the classification and detection of spoofing signals can be realized. Firstly, the rotating single-antenna receiver collects carrier-phase values and performs double-difference processing. Then, we construct an IPNN model, whose smoothing factor can be adaptively adjusted according to the type of failure mode. Finally, we use the IPNN model to realize the classification and processing of the carrier-phase double-difference observations and obtain the deception detection results. In addition, in order to reflect that the method has a certain practical value, we simulate the spoofing scenario of satellite signals and effectively identify abnormal satellite signals according to the detection results of the inter-satellite differential combination. Actual experiments indicate that the detection accuracy of the proposed method for spoofing signals reaches 98.84%, which is significantly better than the classical probabilistic neural network (PNN) and back-propagation neural network (BPNN), and the method can be implemented in fixed base station receivers for the real-time detection of forwarding spoofing.

Enhancing the functional characteristics of soy protein isolate via cross-linking catalyzed by Bacillus subtilis transglutaminase.

BACKGROUND: Although Streptomyces mobaraense transglutaminase (MTG) has been extensively applied to enhance the functional characteristics of soy protein isolate (SPI) through cross-linking, various transglutaminases (TGs) in nature may provide more choice in the food industry. Previous research reported that TG derived from Bacillus subtilis (BTG) exhibited better pH stability and thermostability than MTG. RESULTS: An attempt was made to study the influence of BTG induced cross-linking on the properties of SPI. Sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) results indicated that almost all protein constituents (α', α, ß, AS, and BS) in SPI could be cross-linked with BTG treatment. The BTG treatment also resulted in a significant increase (*P < 0.05) in SPI mean particle size. Emulsifying activity and stability were improved from 0.11535 m2  g-1 and 48.3% for native SPI to 0.13252 m2  g-1 and 83.9% for SPI treated with BTG at 6 h. Similarly, the modified SPI showed better foam activity (1.32 mL) and stability (87.6%) than the original SPI (0.93 mL and 56.8%). The water-holding capacity of SPI gel was found to increase with time, with a value of 95.43% at 6 h. Furthermore, SPI gel's texture profiles were greatly improved by adding BTG (*P < 0.05). CONCLUSION: The results of the present study indicated that BTG could be a promising cross-linking agent for improving the functional characteristics of SPI. As a substitute for MTG, BTG could thus potentially be used for food structure engineering to enhance the functional characteristics of multiple proteins to advance the development of food chemistry. © 2020 Society of Chemical Industry.

Integrated metabolomic and transcriptomic analysis reveals the effects and mechanisms of Jinqi Jiangtang tablets on type 2 diabetes.

BACKGROUND: Type 2 diabetes (T2DM) is one of the major metabolic diseases and poses a serious challenge to human life and global economic development. Jinqi Jiangtang Tablets (JQJT) is effective in ameliorating the effects of T2DM, but the mechanism of JQJT is unclear. PURPOSE: This study integrated metabolomics and transcriptomics to reveal the mechanism by which JQJT improves T2DM. METHODS: The T2DM mouse model was established, and the effects of JQJT on improving T2DM were evaluated by determining the levels of blood lipids, fasting blood glucose (FBG), insulin metabolism and hepatic lipid accumulation in mice after JQJT administration for 8 weeks. Serum metabolites were detected using ultra-performance liquid chromatography/quadrupole time-of-flight-tandem mass spectrometry (UPLC-Q-TOF-MS) technology, and mouse liver differential genes were detected using transcriptomic technology. Correlation analysis was used to extract metabolites and RNA with correlations, and potential pathways were enriched and constructed using the common pathway analysis function of MetaboAnalyst 5.0. Finally, the expression of key target proteins and genes was verified by Western blot (WB) and Polymerase Chain Reaction (PCR) to further elucidate the mechanism by which JQJT improves T2DM. RESULTS: JQJT reduced FBG and lipid levels, improved insulin resistance (IR) and hepatic lipoatrophy in mice. A total of 35 differentially abundant metabolites were identified by metabolomics, and 328 differential genes were detected by transcriptomics. The integrated metabolomics and transcriptomics results suggested that JQJT may ameliorate T2DM mainly by regulating glucose and lipid metabolic pathways. WB and PCR results showed that JQJT regulates the insulin signaling pathway, involved in fatty acid metabolism, glycogen synthesis and catabolism. CONCLUSIONS: JQJT improved IR in T2DM mice by regulating the insulin signaling pathway, improving glycogen synthesis and glycolysis, and increasing hepatic triglyceride and fatty acid metabolism.

Inflammation and coronary microvascular disease: relationship, mechanism and treatment.

Coronary microvascular disease (CMVD) is common in patients with cardiovascular risk factors and is linked to an elevated risk of adverse cardiovascular events. Although modern medicine has made significant strides in researching CMVD, we still lack a comprehensive understanding of its pathophysiological mechanisms due to its complex and somewhat cryptic etiology. This greatly impedes the clinical diagnosis and treatment of CMVD. The primary pathological mechanisms of CMVD are structural abnormalities and/or dysfunction of coronary microvascular endothelial cells. The development of CMVD may also involve a variety of inflammatory factors through the endothelial cell injury pathway. This paper first reviews the correlation between the inflammatory response and CMVD, then summarizes the possible mechanisms of inflammatory response in CMVD, and finally categorizes the drugs used to treat CMVD based on their effect on the inflammatory response. We hope that this paper draws attention to CMVD and provides novel ideas for potential therapeutic strategies based on the inflammatory response.

Coupling and coordinated development of low-carbon economy and green finance: an empirical study of the Yangtze River Delta region in China.

The introduction of China's double carbon target has led to a new stage in the development of China's low-carbon economy, while the development of China's green finance is also facing new challenges. Based on the determining of the relationship between low-carbon economy and green finance, this study selected the Yangtze River Delta city cluster of China, an exemplary region for the development of low-carbon economy and green finance, constructed a multi-level comprehensive index system covering two systems of low-carbon economy and green finance and conducted a coupled and coordinated relationship analysis based on the panel data of green finance and low-carbon economy-related indicators from 2016 to 2020. The empirical results showed that the interaction between the low-carbon economy system and the green finance system in the Yangtze River Delta region gradually weakened during 2016-2020, and the mechanism of interaction between the two systems has not been fully developed and utilized. Overall, the development of green finance in all four provinces and cities has not gained sufficient momentum, which is a constraint to the coupled and coordinated development of low-carbon economy and green finance in the four provinces and cities in the Yangtze River Delta. Zhejiang Province and Jiangsu Province performed better in terms of the scale of green finance and the use of diversified instruments, while Shanghai City performed better in terms of low-carbon economy, whereas Anhui Province needs to improve in both low-carbon economy and green finance.

LncIRF1 promotes chicken resistance to ALV-J infection.

The pathogenesis of avian leukosis virus subgroup J (ALV-J) is complex and our understanding of it is limited. Based on our previous research, we explored the relationship between ALV-J infection and regulatory factor 1&7 (IRF1 and IRF7), interferon beta (IFNß), and the newly identified long noncoding RNA IRF1 (LncIRF1). LncIRF1 is 1603 nt and exists in the cytoplasm and nucleus. After the occurrence of ALV-J infection, the expression levels of LncIRF1, IRF1, IRF7, and IFNß varied in different chicken tissues. In DF1 cell lines of chicken embryo fibroblast cells (DF1 cells) the expression levels of LncIRF1, IRF7, IRF1, and IFNß increased when ALV-J infection. Similarly, after LncIRF1 overexpression and the ALV-J challenge, the expression levels of IRF1, IRF7, and IFNß increased, while increased LncIRF1 inhibited the proliferation of DF1 cells. Interference with LncIRF1 did not affect IRF1, IRF7, and IFNß. However, expression levels of IRF1, IRF7, and IFNß decreased due to LncIRF1 interference after the ALV-J challenge. An assay of the RNA-binding domain abundant in apicomplexans indicated that most of the proteins bound to LncIRF1 are related to cell proliferation and viral replication and these proteins also interact with IRF1, IRF7, and IFNß. We suggest that LncIRF1 plays an important immunomodulatory role in the anti-ALV-J response. Supplementary Information: The online version contains supplementary material available at 10.1007/s13205-023-03773-y.

Gut microbiota: A new target of traditional Chinese medicine for insomnia.

All species have a physiological need for sleep, and sleep is crucial for the preservation and restoration of many physiological processes in the body. Recent research on the effects of gut microbiota on brain function has produced essential data on the relationship between them. It has been discovered that dysregulation of the gut-brain axis is related to insomnia. Certain metabolites of gut microbiota have been linked to insomnia, and disturbances in gut microbiota can worsen insomnia. Traditional Chinese medicine (TCM) has unique advantages for the treatment of insomnia. Taking the gut microbiota as the target and determining the scientific relevance of TCM to the prevention and treatment of insomnia may lead to new concepts for the treatment of sleep disorders and improve the therapeutic effect of sleep. Taking the gut microbiota as an entry point, this paper reviews the relationship between gut microbiota and TCM, the relationship between gut microbiota and insomnia, the mechanism by which gut microbiota regulate sleep, and the mechanism by which TCM regulates gut microbiota for insomnia prevention and treatment. This review provides new ideas for the prevention and treatment of insomnia through TCM and new ideas for drug development.

Targeting metabolic pathways: a novel therapeutic direction for type 2 diabetes.

Background: Type 2 diabetes mellitus (T2DM) is a prevalent metabolic disease that causes multi-organ complications, seriously affecting patients' quality of life and survival. Understanding its pathogenesis remains challenging, with current clinical treatment regimens often proving ineffective. Methods: In this study, we established a mouse model of T2DM and employed 16s rDNA sequencing to detect changes in the species and structure of gut flora. Additionally, we used UPLC-Q-TOF-MS to identify changes in urinary metabolites of T2DM mice, analyzed differential metabolites and constructed differential metabolic pathways. Finally, we used Pearman correlation analysis to investigate the relationship between intestinal flora and differential metabolites in T2DM mice, aiming to elucidate the pathogenesis of T2DM and provide an experimental basis for its clinical treatment. Results: Our findings revealed a reduction in both the species diversity and abundance of intestinal flora in T2DM mice, with significantly decreased levels of beneficial bacteria such as Lactobacillus and significantly increased levels of harmful bacteria such as Helicobacter pylori. Urinary metabolomics results identified 31 differential metabolites between T2DM and control mice, including Phosphatidylcholine, CDP-ethanolamine and Leukotriene A4, which may be closely associated with the glycerophospholipid and arachidonic acid pathways. Pearman correlation analysis showed a strong correlation between dopamine and gonadal, estradiol and gut microbiota, may be a novel direction underlying T2DM. Conclusion: In conclusion, our study suggests that alterations in gut microbiota and urinary metabolites are characteristic features of T2DM in mice. Furthermore, a strong correlation between dopamine, estradiol and gut microbiota, may be a novel direction underlying T2DM, the aim is to provide new ideas for clinical treatment and basic research.

Targeting mitochondrial circadian rhythms: The potential intervention strategies of Traditional Chinese medicine for myocardial ischaemia‒reperfusion injury.

Coronary artery disease has one of the highest mortality rates in the country, and methods such as thrombolysis and percutaneous coronary intervention (PCI) can effectively improve symptoms and reduce mortality, but most patients still experience symptoms such as chest pain after PCI, which seriously affects their quality of life and increases the incidence of adverse cardiovascular events (myocardial ischaemiareperfusion injury, MIRI). MIRI has been shown to be closely associated with circadian rhythm disorders and mitochondrial dysfunction. Mitochondria are a key component in the maintenance of normal cardiac function, and new research shows that mitochondria have circadian properties. Traditional Chinese medicine (TCM), as a traditional therapeutic approach characterised by a holistic concept and evidence-based treatment, has significant advantages in the treatment of MIRI, and there is an interaction between the yin-yang theory of TCM and the circadian rhythm of Western medicine at various levels. This paper reviews the clinical evidence for the treatment of MIRI in TCM, basic experimental studies on the alleviation of MIRI by TCM through the regulation of mitochondria, the important role of circadian rhythms in the pathophysiology of MIRI, and the potential mechanisms by which TCM regulates mitochondrial circadian rhythms to alleviate MIRI through the regulation of the biological clock transcription factor. It is hoped that this review will provide new insights into the clinical management, basic research and development of drugs to treat MIRI.

The add-on effect of Shufeng Jiedu capsule for treating COVID-19: A systematic review and meta-analysis.

Introduction: Shufeng Jiedu capsule (SFJD) is a commonly used Chinese patent medicine in China. Some studies have reported that SFJD has therapeutic effects in patients diagnosed with COVID-19. This systematic review aimed to critically evaluate the efficacy and safety of SFJD combined with western medicine (WM) for treating COVID-19. Methods: A literature search by using WHO COVID-19 database, PubMed, Embase, Cochrane Library, the Web of Science, CKNI, Wanfang, VIP, SinoMed, and clinical trial registries was conducted, up to 1 August 2022. Randomized controlled trials (RCTs), non-RCTs, cohort studies and case series of SFJD combined with WM for COVID-19 were included. Literature screening, data extraction, and quality assessment were performed independently by two reviewers in line with the same criteria. We used the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) to assess the certainty of evidence. Meta-analyses were performed with Revman 5.3 if possible. The descriptive analysis was conducted when the studies could not be meta-analyzed. Results: Totally 10 studies with 1,083 patients were included. Their methodological quality were moderate. The results demonstrated that compared to WM group, SFJD + WM group remarkably increased the nucleic acid negative conversion rate (RR = 1.40, 95%CI: 1.07-1.84), total effective rate (RR = 1.18, 95%CI: 1.07-1.31), cure rate (RR = 4.06, 95%CI: 2.19-7.53), and the chest CT improvement rate (RR = 1.19, 95%CI: 1.08-1.31), shorten nucleic acid negative conversion time (MD = -0.70, 95%CI: -1.14 to -0.26), reduced the clinical symptom disappearance time (fever, diarrhea, cough, fatigue, pharyngalgia, nasal congestion, and rhinorrhea), as well as improved the levels of laboratory outcomes (CRP, IL-6, Lym, and Neu). Additionally, the incidence of adverse reactions did not exhibit any statistically significant difference between SFJD + WM group and WM group. Conclusion: SFJD combined with WM seems more effective than WM alone for the treatment of COVID-19. However, more well-designed RCTs still are warranted. Systematic review registration: [https://www.crd.york.ac.uk/PROSPERO/], identifier [CRD42022306307].

Utilization of Soybean Oil Waste for a High-Level Production of Ceramide by a Novel Phospholipase C as an Environmentally Friendly Process.

Ceramide is a natural functional ingredient as food additive and medicine that has attracted extensive attention in the food, medical, and cosmetic industries. Here, we developed a biotechnological strategy based on a recombinant whole-cell biocatalyst for efficiently producing ceramide from crude soybean oil sediment (CSOS) waste. A novel phospholipase C (PLCac) from Acinetobacter calcoaceticus isolated from soil samples was identified and characterized. Furthermore, recombinant Komagataella phaffii displaying PLCac (dPLCac) on the cell surface was constructed as a whole-cell biocatalyst with better thermostability (30-60 °C) and pH stability (8.0-10.0) to successfully produce ceramide. After synergistical optimization of reaction time and dPLCac dose, the ceramide yield of hydrolyzing from CSOS using dPLCac was 51% (the theoretical maximum yield of converting sphingomyelin, ∼70%) and the relative yield was over 50% after seven consecutive 4 h batches under the optimized conditions. Our study provides a potentially promising strategy for the commercial production of ceramide.

Biochemical characterization of a tyrosinase from Bacillus aryabhattai and its application.

Although lots of tyrosinases have been isolated from bacteria, few studies are focused on tyrosinases from Bacillus sp.. In this study, a tyrosinase from B. aryabhattai TCCC 111983 (TYR) was functionally expressed, purified, and then biochemically characterized. The recombinant tyrosinase (rTYR) presented a good catalytic activity in a broad temperature and pH range, retaining over 60% of the relative activity at 30 °C-90 °C and 45% at pH 3.0 to 10.0. Especially, rTYR exhibited 20% of its maximum activity at 0 °C, and it also showed a variable stability towards different effectors. It presented high tolerance towards salinity and chloride, retaining 81% of its original activity in 2 M NaCl. Kinetic parameters indicated that rTYR displayed a relatively good affinity for both l-tyrosine and l-DOPA. Additionally, rTYR demonstrated remarkable advantages on efficient decolorizing azo and anthraquinonic food dyes (carmine and erythrosin), and more five industrial dyes with or without mediators in acidic, neutral, and alkaline conditions. As the first report on the tyrosinase from B. aryabhattai, the aforementioned results indicated that rTYR would be potential for food industrial applications.

Enzymatic characterization, molecular dynamics simulation, and application of a novel Bacillus licheniformis laccase.

A new laccase gene from newly isolated Bacillus licheniformis TCCC 111219 was actively expressed in Escherichia coli. This recombinant laccase (rLAC) exhibited a high stability towards a wide pH range and high temperatures. 170% of the initial activity was detected at pH 10.0 after 10-d incubation, and 60% of the initial activity was even kept after 2-h incubation at 70 °C. It indicated that only single type of extreme environment, such as strong alkaline environment (300 K, pH 12) or high temperature (370 K, pH 7), did not show obvious impact on the structural stability of rLAC during molecular dynamics simulation process. But the four loop regions of rLAC where the active site is situated were seriously destroyed when strong alkaline and high temperature environment existed simultaneously (370 K, pH 12) because of the damage of hydrogen bonds and salt bridges. Moreover, this thermo- and alkaline-stable enzyme could efficiently decolorize the structurally differing azo, triphenylmethane, and anthraquinone dyes with appropriate mediator at pH 3.0, 7.0, and 9.0 at 60 °C. These rare characteristics suggested its high potential in industrial applications to decolorize textile dyeing effluent.

Preparation of Microcapsules Coating and the Study of Their Bionic Anti-Fouling Performance.

With the increasing demands to better the marine environment, environmentally friendly anti-fouling coatings have attracted attention from society. Adding hydrolyzable microcapsules without toxin to paints is a very useful and safe method to get bionic anti-fouling coatings with a micro-nano surface structure. Based on this trend, a form of environment-friendly microcapsules were prepared through mini-emulsion polymerization. The target microcapsules had a poly(urea-formaldehyde) (PUF) shell and a mixed core of silicone oil and capsaicin. Additionally, the microcapsules were introduced into zinc acrylate resin to obtain bionic anti-fouling coatings with micro-nano morphology. The effects of polyvinyl alcohol (PVA) molecular weight, stirring rate, and temperature on the morphology of the microcapsules were studied by optical microscopy (OM), scanning electron microscopy (SEM) and transmission electron microscopy (TEM). It was found that spherical nanoparticles with smooth surfaces were obtained, and the mean diameter was approximately 1.38 µm when the molecular weight of PVA was 77 K, the stirring rate was 600 rpm and the temperature was 55 °C. Fourier-transform infrared spectra (FTIR) results showed that the silicone oil and capsaicin were successfully encapsulated, the core materials of the microcapsules reached 72.37% and the yield of microcapsules was 68.91% by the Soxhlet method. Furthermore, the hydrophobicity, corrosion resistance and anti-fouling performance of the coatings were evaluated by the water contact angle, electrochemical and real-sea tests. The results indicated that the anti-fouling coatings had excellent hydrophobicity and anti-fouling performance due to the micro-nano convex structure and the release of core materials. Encouragingly, the anti-fouling coatings show excellent and long-term anti-fouling performance, which is expected to be widely applied in marine anti-fouling coatings.