A 44-cm3 physics package for the high-performance pulsed optically pumped atomic clock.

The pulsed optically pumped (POP) atomic clock has demonstrated unexpected performance in terms of frequency stability and drift. However, it remains a huge challenge to make this type of atomic clock more compact. Herein, we report the design of a miniaturized physics package, which is equipped with a magnetron microwave cavity holding a vapor cell of 1.3 cm internal diameter. The Zeeman transition spectrum reveals that the microwave cavity resonates in TE011-like mode. Based on a low-noise testbed, we also quantitatively analyze the relaxation time, linewidth, and noise sources of the resulting POP atomic clock. The population and coherence relaxation time are measured to be 3.16(0.16) and 2.97(0.03) ms under the temperature of 333 K, which are compatible well with the theoretical calculation. The Ramsey signal shows a contrast of 35% and a linewidth of 192 Hz. The total volume of the physics package is about 44 cm3, including a layer of magnetic shielding. The short-term frequency stability is measured to be 4.8 × 10-13τ-1/2 (where τ is the averaging time), which is mainly limited by the relative intensity noise of the laser system.

Association between dietary niacin intake and risk of Parkinson's disease in US adults: cross-sectional analysis of survey data from NHANES 2005-2018.

Parkinson's disease (PD) is one of the most common neurodegenerative diseases and involves various pathogenic mechanisms, including oxidative stress and neuroinflammation. Niacin, an important cofactor in mitochondrial energy metabolism, may play a key role in the pathogenesis of PD. An in-depth exploration of the relationship between niacin and mitochondrial energy metabolism may provide new targets for the treatment of PD. The present study was designed to examine the association between dietary niacin intake and the risk of PD in US adults. Data from adults aged 40 years and older collected during cycles of the United States (US) National Health and Nutrition Examination Survey (NHANES) from 2005 to 2018 were used. A multiple logistic regression model was used to analyze the relationship between dietary niacin intake and the risk of PD. Further linear tests using restricted cubic splines (RCS) were performed to explore the shape of the dose-response relationship. Subgroup stratification and interaction analyses were conducted according to years of education, marital status, smoking, and hypertension to evaluate the stability of the association between different subgroups. A total of 20,211 participants were included in this study, of which 192 were diagnosed with PD. In the fully adjusted multiple logistic regression model, dietary niacin intake was negatively associated with the risk of PD (OR: 0.77, 95%CI: 0.6-0.99; p = 0.042). In the RCS linear test, the occurrence of PD was negatively correlated with dietary niacin intake (nonlinearity: p = 0.232). In stratified analyses, dietary niacin intake was more strongly associated with PD and acted as an important protective factor in patients with fewer years of education (OR: 0.35, 95%CI: 0.13-0.93), married or cohabitating (OR: 0.71, 95%CI: 0.5-0.99), taking dietary supplements (OR: 0.6, 95%CI: 0.37 0.97), non-smokers (OR: 0.57, 95%CI: 0.39-0.85), those with hypertension (OR: 0.63, 95%CI: 0.63-0.95), coronary artery disease (OR: 0.77, 95%CI: 0.6-1), and stroke (OR: 0.75, 95%CI: 0.88-0.98), but the interaction was not statistically significant in all subgroups. Dietary niacin intake was inversely associated with PD risk in US adults, with a 23% reduction in risk for each 10 mg increase in niacin intake.

[Effects and mechanisms of electroacupuncture on fear extinction and sleep phase in single prolonged stress mice].

OBJECTIVE: To observe the effects of electroacupuncture (EA) on fear extinction and sleep phase in single prolonged stress (SPS) mice, and explore its mechanism in view of the expression of relevant synaptic proteins. METHODS: Thirty-two C57BL/6J male mice were randomly divided into a control group, a model group, an EA group and a paroxetine (PRX) group, with 8 mice in each one. Modified SPS method was used to establish PTSD model in the model group, the EA group and the PRX group. Seven days after modeling completion, in the EA group, the intervention was delivered at "Baihui" (GV 20) and bilateral "Zusanli" (ST 36), with disperse-dense wave, 3 Hz/15 Hz in frequency and 1 mA in current intensity, for 30 min. In the PRX group, paroxetine solution (2.5 g/L) was administered intragastrically (10 mg/kg). The intervention was given once daily and for consecutive 10 days in the above two groups. The fear conditioning task and the elevated plus-maze test were adopted to evaluate the fear extinction and anxiety of the mice in each group. Using Medusa electroencephalogram (EEG) and electromyography (EMG) recording system from rats and mice, the sleep phase was determined in the mice. With Western blot method adopted, the protein expression of the postsynaptic density protein 95 (PSD95), activity-regulated cytoskeleton-associated protein (ARC), brain-derived neurotrophic factor (BDNF), N-methyl-D-aspartic acid receptor 2A (GluN2A), N-methyl-D-aspartic acid receptor 2B (GluN2B) and alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid receptor 1 (GluA1) in the hippocampus was detected in the mice. RESULTS: Compared with the control group, the freezing time for the fear re-exposure in 3 min to 15 min and the fear extinction in 0 min to 3 min were prolonged (P<0.05), the fear extinction index decreased (P<0.05), and the open arm time (OT) of the elevated plus-maze was shortened (P<0.05) in the model group. When compared with the model group, in the EA group and the PRX group, the freezing time for the fear re-exposure in 3 min to 6 min and 12 min to 15 min, as well as the fear extinction in 0 min to 3 min was shortened (P<0.05), the fear extinction index increased (P<0.05); the OT in elevated plus-maze was longer in the mice of the EA group (P<0.05). The period of wake (Wake) was prolonged (P<0.05), the non-rapid eye movement period (NREM) and the total sleep time (Sleep) were reduced in the model group (P<0.05) in comparison with the control group. Compared with the model group, the Wake was declined (P<0.05), and the NREM and Sleep increased in the EA group and the PRX group (P<0.05). When compared with the control group, the protein expression of PSD95, ARC, BDNF, GluN2A and GluA1 in the hippocampus decreased (P<0.05), and that of GluN2B increased (P<0.05) in the model group. In the EA group and the PRX group, the protein expression of PSD95, ARC, BDNF, GluN2A and GluA1 in the hippocampus was elevated (P<0.05), and that of GluN2B reduced (P<0.05) when compared with the model group. CONCLUSION: Electroacupuncture at "Baihui" (GV 29) and "Zusanli" (ST 36) can ameliorate anxiety-like behavior, fear extinction disorder and abnormal sleep phase in SPS mice, which may be related to the regulation of synaptic transmission and synaptic plasticity expression in the hippocampus.

Activation of GPER1 by G1 prevents PTSD-like behaviors in mice: Illustrating the mechanisms from BDNF/TrkB to mitochondria and synaptic connection.

BACKGROUND: G1 is a specific agonist of G protein-coupled estrogen receptor 1 (GPER1), which binds and activates GPER1 to exert various neurological functions. However, the preventive effect of G1 on post-traumatic stress disorder (PTSD) and its mechanisms are unclear. OBJECTIVE: To evaluate the protective effect of G1 against synaptic and mitochondrial impairments and to investigate the mechanism of G1 to improve PTSD from brain-derived neurotrophic factor (BDNF)/tyrosine kinase receptor B (TrkB) signaling. METHODS: This study initially detected GPER1 expression in the hippocampus of single prolonged stress (SPS) mice, utilizing both Western blot and immunofluorescence staining. Subsequently, the effects of G1 on PTSD-like behaviors, synaptic, and mitochondrial functions in SPS mice were investigated. Additionally, the involvement of BDNF/TrkB signaling involved in the protection was further confirmed using GPER1 antagonist and TrkB inhibitor, respectively. RESULTS: The expression of GPER1 was reduced in the hippocampus of SPS mice, and G1 treatment given for 14 consecutive days significantly improved PTSD-like behaviors in SPS mice compared with model group. Electrophysiological local field potential (LFP) results showed that G1 administration for 14 consecutive days could reverse the abnormal changes in the gamma oscillation in the CA1 region of SPS mice. Meanwhile, G1 administration for 14 consecutive days could significantly improve the abnormal expression of synaptic proteins, increase the expression of mitochondria-related proteins, increase the number of synapses in the hippocampus, and ameliorate the damage of hippocampal mitochondrial structure in SPS mice. In addition, G15 (GPER1 inhibitor) and ANA-12 (TrkB inhibitor) blocked the ameliorative effects of G1 on PTSD-like behaviors and aberrant expression of hippocampal synaptic and mitochondrial proteins in SPS mice and inhibited the reparative effects of G1 on structural damage to hippocampal mitochondria, respectively. CONCLUSION: G1 improved PTSD-like behaviors in SPS mice, possibly by increasing hippocampal GPER1 expression and promoting BDNF/TrkB signaling to repair synaptic and mitochondrial functional impairments. This study would provide critical mechanism for the prevention and treatment of PTSD.

Novel mechanisms of Anshen Dingzhi prescription against PTSD: Inhibiting DCC to modulate synaptic function and inflammatory responses.

ETHNOPHARMACOLOGICAL RELEVANCE: Anshen Dingzhi prescription (ADP), documented in "Yi Xue Xin Wu", is a famous prescription for treating panic-related mental disorders such as post-traumatic stress disorder (PTSD). However, the underlying mechanism remains unclear. AIM OF THE STUDY: This study aimed to investigate the mechanisms by which ADP intervened in PTSD-like behaviors. METHODS: A mouse model of single prolonged stress (SPS) was established to evaluate the ameliorative effects and mechanisms of ADP on PTSD. Behavioral tests were used to assess PTSD-like behaviors in mice; transmission electron microscopy was used to observe changes in the ultrastructure of hippocampal synapses, and western blot, immunofluorescence, and ELISA were used to detect the expression of hippocampal deleted in colorectal cancer (DCC) and downstream Ras-related C3 botulinum toxin substrate 1 (Rac1) - P21-activated kinase 1 (PAK1) signal, as well as levels of synaptic proteins and inflammatory factors. Molecular docking technology simulated the binding of potential brain-penetrating components of ADP to DCC. RESULTS: SPS induced PTSD-like behaviors in mice and increased expression of hippocampal netrin-1 (NT-1) and DCC on the 14th day post-modeling, with concurrent elevation in serum NT-1 levels. Simultaneously, SPS also decreased p-Rac1 level and increased p-PAK1 level, the down-stream molecules of DCC. Lentiviral overexpression of DCC induced or exacerbated PTSD-like behaviors in control and SPS mice, respectively, whereas neutralization antibody against NT-1 reduced DCC activation and ameliorated PTSD-like behaviors in SPS mice. Interestingly, downstream Rac1-PAK1 signal was altered according to DCC expression. Moreover, DCC overexpression down-regulated N-methyl-d-aspartate (NMDA) receptor 2A (GluN2A) and postsynaptic density 95 (PSD95), up-regulated NMDA receptor 2B (GluN2B) and increased neuroinflammatory responses. Administration of ADP (36.8 mg/kg) improved PTSD-like behaviors in the SPS mice, suppressed hippocampal DCC, and downstream Rac1-PAK1 signal, upregulated GluN2A and PSD95, downregulated GluN2B, and reduced levels of inflammatory factors NOD-like receptor protein 3 (NLRP3), nuclear factor kappa-B (NF-κB) and interleukin-6 (IL-6). Importantly, DCC overexpression could also reduce the ameliorative effect of ADP on PTSD. Additionally, DCC demonstrated a favorable molecular docking pattern with the potential brain-penetrating components of ADP, further suggesting DCC as a potential target of ADP. CONCLUSION: Our data indicate that DCC is a key target for the regulation of synaptic function and inflammatory response in the onset of PTSD, and ADP likely reduces DCC to prevent PTSD via modulating downstream Rac1-PAK1 pathway. This study provides a novel mechanism for the onset of PTSD and warrants the clinical application of ADP.

The role of pyroptosis in metabolism and metabolic disease.

Pyroptosis is a lytic and pro-inflammatory form of regulated cell death characterized by the formation of membrane pores mediated by the gasdermin protein family. Two main activation pathways have been documented: the caspase-1-dependent canonical pathway and the caspase-4/5/11-dependent noncanonical pathway. Pyroptosis leads to cell swelling, lysis, and the subsequent release of inflammatory mediators, including interleukin-1ß (IL-1ß) and interleukin-18 (IL-18). Chronic inflammation is a well-established foundation and driver for the development of metabolic diseases. Conversely, metabolic pathway dysregulation can also induce cellular pyroptosis. Recent studies have highlighted the significant role of pyroptosis modulation in various metabolic diseases, including type 2 diabetes mellitus, obesity, and metabolic (dysfunction) associated fatty liver disease. These findings suggest that pyroptosis may serve as a promising novel therapeutic target for metabolic diseases. This paper reviews an in-depth study of the current advancements in understanding the role of pyroptosis in the progression of metabolic diseases.

Recognizing Alzheimer's disease from perspective of oligodendrocytes: Phenomena or pathogenesis?

BACKGROUND: Accumulation of amyloid beta, tau hyperphosphorylation, and microglia activation are the three highly acknowledged pathological factors of Alzheimer's disease (AD). However, oligodendrocytes (OLs) were also widely investigated in the pathogenesis and treatment for AD. AIMS: We aimed to update the regulatory targets of the differentiation and maturation of OLs, and emphasized the key role of OLs in the occurrence and treatment of AD. METHODS: This review first concluded the targets of OL differentiation and maturation with AD pathogenesis, and then advanced the key role of OLs in the pathogenesis of AD based on both clinic and basic experiments. Later, we extensively discussed the possible application of the current progress in the diagnosis and treatment of this complex disease. RESULTS: Molecules involving in OLs' differentiation or maturation, including various transcriptional factors, cholesterol homeostasis regulators, and microRNAs could also participate in the pathogenesis of AD. Clinical data point towards the impairment of OLs in AD patients. Basic research further supports the central role of OLs in the regulation of AD pathologies. Additionally, classic drugs, including donepezil, edaravone, fluoxetine, and clemastine demonstrate their potential in remedying OL impairment in AD models, and new therapeutics from the perspective of OLs is constantly being developed. CONCLUSIONS: We believe that OL dysfunction is one important pathogenesis of AD. Factors regulating OLs might be biomarkers for early diagnosis and agents stimulating OLs warrant the development of anti-AD drugs.

Enhancing citric acid tolerance of Acetobacter tropicalis using chemical and physical mutagenesis and adaptive evolution to improve the quality of lemon fruit vinegar.

The high concentration of citric acid in lemons limits the production of lemon fruit vinegar because it inhibits the metabolism of acetic acid bacteria and reduces the utilization of raw materials. This study aimed to enhance the citric acid tolerance of Acetobacter tropicalis by using complex mutagenesis and adaptive laboratory evolution (ALE) and improving the quality of lemon fruit vinegar. After mutagenesis and ALE, A. tropicalis JY-135 grew well under 40 g/L citric acid, and it showed high physiological activity and excellent fermentation performance under high concentrations of citric acid. The survival rate and ATP content of JY-135 were 15.27 and 9.30 times higher than that of the original strain J-2736. In the fermentation of lemon fruit vinegar, the acid production and the number of aroma-active compounds were 1.61-fold and 2.17-fold than J-2736. In addition, we found that citric acid tolerance of JY-135 is related to the respiratory electron-transport chain and the tricarboxylic acid (TCA) cycle. This work is of great significance for the production of high-quality lemon fruit vinegar and the enrichment of seed resources of acetic acid bacteria.

Association between plasma CTRPs with cognitive impairment and neurodegeneration of Alzheimer's disease.

AIMS: Recent evidence indicated the biological basis of complement 1q (C1q)/tumor necrosis factor (TNF)-related protein (CTRP) 3, 4, and 14 for affecting brain structure and cognitive function. Thus, we aimed to investigate the association between plasma CTRPs with Alzheimer's disease (AD). METHODS: A multicenter, cross-sectional study recruited patients with AD (n = 137) and cognitively normal (CN) controls (n = 140). After the data collection of demographic characteristics, lifestyle risk factors, and medical history, plasma levels of tau phosphorylated at threonine 217 (pT217), pT181, neurofilament light (NfL), CTRP3, 4, and 14 were examined and compared. Multivariate logistic regression analysis was applied to determine associations of plasma CTPRs with the presence of AD. The correlation analysis was used to explore correlations between plasma CTPRs with scores of Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment (MoCA), Activities of Daily Living (ADL) scale, and Clinical Dementia Rating Sum of Boxes (CDR-SB), and levels of plasma pT217, pT181, and NfL. Receiver-operating characteristic (ROC) analysis and Delong's test were used to determine the diagnostic power of plasma CTPRs. RESULTS: Plasma levels of CTRP3, 4, and 14 were higher in AD group than those in CN group. After adjusting for conventional risk factors, CTRP3, CTRP4, and CTRP14 were associated with the presence of AD. In AD patients, CTRP3 was negatively correlated with scores of MMSE and MoCA, while positively correlated with ADL score, CDR-SB score, pT217, and pT181; CTRP4 was positively correlated with CDR-SB score, pT181, and NfL; CTRP14 was negatively correlated with MMSE score, while positively correlated with CDR-SB score, pT217, and NfL. An independent addition of CTRP3 and 4 to the basic model combining age, sex, years of education, APOE4 status, BMI, TG, and HDL-C led to a significant improvement in diagnostic power for AD, respectively. CONCLUSIONS: All the findings preliminarily uncovered associations between plasma CTRPs and AD and suggested the potential of CTRPs as a blood-derived biomarker for AD.

Exploring the effect of Anshen Dingzhi prescription on hippocampal mitochondrial signals in single prolonged stress mouse model.

HEADINGS ETHNOPHARMACOLOGICAL RELEVANCE: Anshen Dingzhi prescription (ADP), which was first published in the masterpiece of traditional Chinese Medicine in the Qing Dynasty, "Yi Xue Xin Wu" (1732 CE), is documented to interrupt panic-related disorders. However, the mechanism of its action is still not clear. AIM OF THE STUDY: This study aims to investigate the effects of ADP on post-traumatic stress disorder (PTSD)-like behaviors and explore the mechanism from perspective of sirtuin1 (SIRT1)-peroxisome proliferator-activated receptor gamma co-activator 1 alpha (PGC-1α)-dependent mitochondrial function. MATERIALS AND METHODS: The changes of SIRT1-PGC-1α signal and mitochondrial function were evaluated in the hippocampus of mice receiving single prolonged stress (SPS). Later, the roles of this signaling pathway played in fear memory generalization and anxiety-like behavior in SPS mice was investigated using two agonists of this signaling pathway. On this basis, the effects of ADP (36.8 mg/kg) with definite therapeutic effects, on mitochondrial function were investigated and further confirmed by a SIRT1 inhibitor. Finally, the possible components of ADP targeting PGC-1α were monitored through bioinformatics. RESULTS: Compared with control mice, SIRT1-PGC-1α signal in the hippocampus was impaired in SPS mice, accompanied with dysfunction of mitochondria and abnormal expression of synaptic proteins. The agonists of SIRT1-PGC-1α signal, ZLN005, as well as resveratrol improved the behavioral changes of mice caused by SPS, reversed the decline of proteins in SIRT1-PGC-1α signal, mitochondrial dysfunction, and the abnormal expression of synaptic proteins. The fingerprint was established for the quality control of ADP. At a dose of 36.8 mg/kg, ADP could prevent fear memory generalization and anxiety-like behavior in SPS mice. Mechanically, ADP promoted SIRT1-PGC-1α signal and repaired mitochondrial function. Importantly, SIRT1 inhibitor, selisistat eliminated the ameliorative effects of ADP on behavioral and mitochondrial function. Through molecular docking simulation, the brain-entering components of ADP, including malkangunin, Rg5, fumarine, frutinone A, celabenzine, and inermin had high binding energy with PGC-1α. CONCLUSION: Dysfunction of SIRT1-PGC-1α-dependent mitochondrial function is attributed to SPS-triggered fear generalization and anxiety-like behavior, and ADP could improve PTSD-like behaviors likely through activating this signaling pathway.

Resistance to Cholesterol Gallstone Disease: Hepatic Cholesterol Metabolism.

Cholesterol gallstone disease (CGD) is one of the most common digestive diseases, and it is closely associated with hepatic cholesterol metabolism. Cholesterol gallstones may be caused by abnormal hepatic cholesterol metabolism, such as excessive cholesterol biosynthesis within the liver, interfering with the uptake or export of cholesterol in the liver, and abnormal hepatic cholesterol esterification. In this review, we begin with a brief overview of the clinical diagnosis and treatment of gallstone disease (GSD). Then, we briefly describe the major processes of hepatic cholesterol metabolism and summarize the key molecular expression changes of hepatic cholesterol metabolism in patients with gallstones. We review and analyze the recent advances in elucidating the relationships between these key molecules and CGD, and some targets significantly impacting on CGD via hepatic cholesterol metabolism are also listed. We also provide a significant discussion on the relationship between CGD and nonalcoholic fatty liver disease (NAFLD). Finally, the new discoveries of some therapeutic strategies associated with hepatic cholesterol metabolism to prevent and treat CGD are summarized.

CHMP3 promotes the progression of hepatocellular carcinoma by inhibiting caspase­1­dependent pyroptosis.

Charged multivesicular body protein 3 (CHMP3) is an elemental constituent of the endosomal sorting complex required for transport (ESCRT) III, whose function as a tumor susceptibility gene in the development of liver cancer remains unclear. CHMP3 was found to be associated with pyroptosis by bioinformatics analysis of data from patients with hepatocellular carcinoma (HCC) in The Cancer Genome Atlas database. It was aimed to explore the role and potential mechanisms of CHMP3 in the development of liver cancer. The expression of CHMP3 at the tissue level was examined using immunohistochemistry and western blot analysis. Subsequently, HepG2 and Huh­7 cells were transfected with small interfering RNA and overexpression plasmids to change CHMP3 expression. The proliferative capacity of cells was examined using colony formation and Cell Counting Kit­8 assays. Wound healing and Transwell assays were used to examine the migratory and invasive abilities of the cells. Transmission electron microscopy was used to observe changes in cell morphology. Western blotting was used to examine the expression of caspase­1 signaling pathway related proteins, a classic pathway of pyroptosis. In addition, a xenograft tumor model was used to examine the tumorigenic ability of CHMP3 in vivo. The results demonstrated that CHMP3 expression was upregulated in HCC and was associated with poor prognosis. Knockdown or overexpression of CHMP3 inhibited or promoted the proliferation, migration and invasion of liver cancer cells. Knockdown of Huh­7 showed changes in cell membrane integrity as well as cytoplasmic leakage. Furthermore, knockdown of CHMP3 may activate the caspase­1 pyroptosis signaling pathway which in turn inhibits the progression of liver cancer, and this effect can be reversed by the caspase­1 inhibitor AYC. In conclusion, CHMP3 may affect the development of liver cancer through the caspase­1­mediated pyroptosis pathway.

Customization of an Ultrafast Thiol-Norbornene Photo-Cross-Linkable Hyaluronic Acid-Gelatin Bioink for Extrusion-Based 3D Bioprinting.

Light-based three-dimensional (3D) bioprinting has been widely studied in tissue engineering. Despite the fact that free-radical chain polymerization-based bioinks like hyaluronic acid methacrylate (HAMA) and gelatin methacryloyl (GelMA) have been extensively explored in 3D bioprinting, the thiol-ene hydrogel system has attracted increasing attention for its ability in building hydrogel scaffolds in an oxygen-tolerant and cell-friendly way. Herein, we report a superfast curing thiol-ene bioink composed of norbornene-modified hyaluronic acid (NorHA) and thiolated gelatin (GelSH) for 3D bioprinting. A new facile approach was first introduced in the synthesis of NorHA, which circumvented the cumbersome steps involved in previous works. Additionally, after mixing NorHA with macro-cross-linker GelSH, the customized NorHA/GelSH bioinks exhibited fascinating superiorities over the gold standard GelMA bioinks, such as an ultrafast curing rate (1-5 s), much lowered photoinitiator concentration (0.03% w/v), and flexible physical performances. Moreover, the NorHA/GelSH hydrogel greatly avoided excess ROS generation, which is important for the survival of the encapsulated cells. Last, compared with the GelMA scaffold, the 3D-printed NorHA/GelSH scaffold not only exhibited excellent cell viability but also guaranteed cell proliferation, revealing its superior bioactivity. In conclusion, the NorHA/GelSH system is a promising candidate for 3D bioprinting and tissue engineering applications.

Angiogenesis-An Emerging Role in Organ Fibrosis.

In recent years, the study of lymphangiogenesis and fibrotic diseases has made considerable achievements, and accumulating evidence indicates that lymphangiogenesis plays a key role in the process of fibrosis in various organs. Although the effects of lymphangiogenesis on fibrosis disease have not been conclusively determined due to different disease models and pathological stages of organ fibrosis, its importance in the development of fibrosis is unquestionable. Therefore, we expounded on the characteristics of lymphangiogenesis in fibrotic diseases from the effects of lymphangiogenesis on fibrosis, the source of lymphatic endothelial cells (LECs), the mechanism of fibrosis-related lymphangiogenesis, and the therapeutic effect of intervening lymphangiogenesis on fibrosis. We found that expansion of LECs or lymphatic networks occurs through original endothelial cell budding or macrophage differentiation into LECs, and the vascular endothelial growth factor C (VEGFC)/vascular endothelial growth factor receptor (VEGFR3) pathway is central in fibrosis-related lymphangiogenesis. Lymphatic vessel endothelial hyaluronan receptor 1 (LYVE1), as a receptor of LECs, is also involved in the regulation of lymphangiogenesis. Intervention with lymphangiogenesis improves fibrosis to some extent. In the complex organ fibrosis microenvironment, a variety of functional cells, inflammatory factors and chemokines synergistically or antagonistically form the complex network involved in fibrosis-related lymphangiogenesis and regulate the progression of fibrosis disease. Further clarifying the formation of a new fibrosis-related lymphangiogenesis network may potentially provide new strategies for the treatment of fibrosis disease.

Causal association between serum total bilirubin and cholelithiasis: a bidirectional two-sample Mendelian randomization study.

Background: Observational studies about the association between serum total bilirubin and cholelithiasis are inconsistent. Hence, it is essential to reevaluate the association between serum total bilirubin and cholelithiasis and to verify whether such association is causal or not. Methods: We selected single-nucleotide polymorphisms (SNPs) that are strongly associated with exposure as instrumental variable and conducted a bidirectional two-sample Mendelian randomization (MR) study to explore the causal association between serum total bilirubin and cholelithiasis. We implemented the inverse-variance weighted approach as a primary analysis to combine the Wald ratio estimates. Four additional analyses, namely, MR-Egger regression, weighted median, weighted mode, and MR-pleiotropy residual sum and outlier (PRESSO), were utilized to investigate the causal association and the influence of potential pleiotropy. Results: A total of 116 SNPs were selected as valid instrumental variables to estimate the causal association of serum total bilirubin on cholelithiasis, and causal association between genetically determined serum total bilirubin and cholelithiasis was demonstrated [beta = 0.10; 95% confident interval (CI), 0.07 to 0.14; p < 0.001]. Likewise, the other methods, namely, the weighted median (beta = 0.12; 95% CI, 0.08 to 0.15; p < 0.001), MR-Egger (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), weighted mode (beta = 0.11; 95% CI, 0.08 to 0.15; p < 0.001), and MR-PRESSO approaches, further confirmed that this result (p = 0.054) indicates similar results. In addition, seven SNPs were selected as instrumental variable to estimate causal association of cholelithiasis on serum total bilirubin, and the result supported the causal effect of cholelithiasis to serum total bilirubin (beta = 0.12; 95% CI, 0.09 to 0.15; p < 0.001). At the same time, the other methods, namely, the weighted median (beta = 0.10; 95% CI, 0.06 to 0.13; p < 0.001), MR-Egger (beta = 0.12; 95% CI, 0.07 to 0.18; p = 0.007), weighted mode (beta = 0.09; 95% CI, 0.03 to 0.14, p = 0.019), and MR-PRESSO methods, further confirmed this result (p < 0.001). Conclusion: Our MR study revealed that the serum total bilirubin was causally associated with the risk of cholelithiasis, and the genetic predisposition to cholelithiasis was causally associated with the increased serum total bilirubin levels.

Phytotherapy of abnormality of fear memory: A narrative review of mechanisms.

It is generally believed that in post-traumatic stress disorder (PTSD), the high expression of fear memory is mainly determined by amygdala hyperactivity and hippocampus hypoactivity. In this review, we firstly updated the mechanisms of fear memory, and then searched the experimental evidence of phytotherapy for fear memory in the past five years. Based on the summary of those experimental studies, we further discussed the future research strategies of plant medicines, including the study of the mechanism of specific brain regions, the optimal time for the prevention and treatment of fear memory-related diseases such as PTSD, and the development of new drugs with active components of plant medicines. Accordingly, plant medicines play a clear role in improving fear memory abnormalities and have the drug development potential in the treatment of fear-related disorders.

Screening and application of purine degrading Limosilactobacillus fermentum LF-1 from Huangjiu fermentation broth.

BACKGROUND: As the important building blocks of nucleic acids, purines are alkaloids and responsible for hyperuricemia and gout. The purine content in Huangjiu is higher, and mainly exists in the form of free bases, which is easier to be absorbed by human body. However, the currently available reports on purine in Huangjiu mainly focus on detection methods and content survey. No studies on the regulation of the purine content in Huangjiu have been reported. RESULTS: Eighty-four strains, with the degradation capacity of purine, were screened from the fermentation broth of Huangjiu. In detail, the isolated lactic acid bacteria (LAB) strain 75 # showed the strongest degradation ability of guanosine, inosine and four purines, which reduce their levels by 83.4% (guanosine), 97.4% (inosine), 95.1% (adenine), 95.0% (guanine), 94.9% (hypoxanthine) and 65.9% (xanthine), respectively. Subsequently, the LAB strain 75# was identified to be Limosilactobacillus fermentum by 16S rRNA gene sequencing, which was named as Limosilactobacillus fermentum LF-1 and applied to the fermentation of Huangjiu in the laboratory. Compared with the fermentation broth of Huangjiu without adding L. fermentum LF-1, the content of purine compounds in the fermentation broth inoculated with L. fermentum LF-1 was reduced by 64.7%. In addition, the fermented Huangjiu had richer flavor compounds, and the physicochemical indices were in accordance with the national standard of Chinese Huangjiu. CONCLUSION: The screened strain L. fermentum LF-1 may be a promising probiotic for the development of a novel that can efficiently degrade purine in Huangjiu. © 2023 Society of Chemical Industry.

In-situ-grown multidimensional Cu-doped Co1-xS2@MoS2 on N-doped carbon nanofibers as anode materials for high-performance alkali metal ion batteries.

Transition metal sulfides with the high theoretical capacity and low cost have been considered as advanced anode candidate for alkali metal ion batteries, but suffered from unsatisfactory electrical conductivity and huge volume expansion. Herein, a multidimensional structure Cu-doped Co1-xS2@MoS2 in-situ-grown on N-doped carbon nanofibers (denoted as Cu-Co1-xS2@MoS2 NCNFs) have been elaborately constructed for the first time. The bimetallic zeolitic imidazolate framework CuCo-ZIFs were encapsulated in the one-dimensional (1D) NCNFs through an electrospinning route and then on which the two-dimensional (2D) MoS2 nanosheets were in-situ grown via a hydrothermal process. The architecture of 1D NCNFs can effectively shorten ion diffusion path and enhance electrical conductivity. Besides, the formed heterointerface between MOF-derived binary metal sulfides and MoS2 can provide extra active centers and accelerate reaction kinetics, which guarantee a superior reversibility. As expected, the resulting Cu-Co1-xS2@MoS2 NCNFs electrode delivers excellent specific capacity of Na-ion batteries (845.6 mAh/g at 0.1 A/g), Li-ion batteries (1145.7 mAh/g at 0.1 A/g), and K-ion batteries (474.3 mAh/g at 0.1 A/g). Therefore, this innovative design strategy will bring a meaningful prospect for developing high-performance multi-component metal sulfides electrode for alkali metal ion batteries.

Effectiveness and safety of central pancreatectomy in benign or low-grade malignant pancreatic body lesions: a systematic review and meta-analysis.

BACKGROUND: The best approach for treating benign or low-grade malignant lesions localized in the pancreatic neck or body remains debatable. Conventional pancreatoduodenectomy and distal pancreatectomy (DP) are associated with a risk of impairment of pancreatic function at long-term follow-up. With advances in technology and surgical skills, the use of central pancreatectomy (CP) has gradually increased. OBJECTIVES: The objective was to compare the safety, feasibility, and short-term and long-term clinical benefits of CP and DP in matched cases. METHODS: The PubMed, MEDLINE, Web of Science, Cochrane, and EMBASE databases were systematically searched to identify studies published from database inception to February 2022 that compared CP and DP. This meta-analysis was performed using R software. RESULTS: Twenty-six studies matched the selection criteria, including 774 CP and 1713 DP cases. CP was significantly associated with longer operative time ( P <0.0001), less blood loss ( P <0.01), overall and clinically relevant pancreatic fistula ( P <0.0001), postoperative hemorrhage ( P <0.0001), reoperation ( P =0.0196), delayed gastric emptying ( P =0.0096), increased hospital stay ( P =0.0002), intra-abdominal abscess or effusion ( P =0.0161), higher morbidity ( P <0.0001) and severe morbidity ( P <0.0001) but with a significantly lower incidence of overall endocrine and exocrine insufficiency ( P <0.01), and new-onset and worsening diabetes mellitus ( P <0.0001) than DP. CONCLUSIONS: CP should be considered as an alternative to DP in selected cases such as without pancreatic disease, length of the residual distal pancreas is more than 5 cm, branch-duct intraductal papillary mucinous neoplasms, and a low risk of postoperative pancreatic fistula after adequate evaluation.

Inflamed Adipose Tissue: Therapeutic Targets for Obesity-related Endothelial Injury.

Cardiovascular disease (CVD) is the leading cause of death worldwide and is primarily associated with obesity, visceral adiposity, and unhealthy perivascular adipose tissue (PVAT). The inflammatory polarization of immune cells residing in adipose tissue and abnormal levels of adipose-related cytokines are crucial factors contributing to the pathogenesis of metabolic disorders. We reviewed the most relevant papers in the English literature regarding PVAT and obesity-related inflammation and CVD, aiming to explore potential therapeutic targets for metabolic alterations related to CV health. Such an understanding will help determine the pathogenetic relationship between obesity and vascular injury in efforts to ameliorate obesity-related inflammatory responses. In the context of obesity, dysregulation of adipose tissue immune function, which consists of immune cells and adipose-derived cytokines, plays a crucial role in vascular injury and endothelial dysfunction, especially the PVAT. Metabolic changes between typical VAT and PVAT in obese conditions would be beneficial in improving the risk of obesity-induced endothelial dysfunction and CVDs.