Stress-Induced Metabolic Disorder in Peripheral CD4+ T Cells Leads to Anxiety-like Behavior.

Physical or mental stress leads to neuroplasticity in the brain and increases the risk of depression and anxiety. Stress exposure causes the dysfunction of peripheral T lymphocytes. However, the pathological role and underlying regulatory mechanism of peripheral T lymphocytes in mood disorders have not been well established. Here, we show that the lack of CD4+ T cells protects mice from stress-induced anxiety-like behavior. Physical stress-induced leukotriene B4 triggers severe mitochondrial fission in CD4+ T cells, which further leads to a variety of behavioral abnormalities including anxiety, depression, and social disorders. Metabolomic profiles and single-cell transcriptome reveal that CD4+ T cell-derived xanthine acts on oligodendrocytes in the left amygdala via adenosine receptor A1. Mitochondrial fission promotes the de novo synthesis of purine via interferon regulatory factor 1 accumulation in CD4+ T cells. Our study implicates a critical link between a purine metabolic disorder in CD4+ T cells and stress-driven anxiety-like behavior.

Multiomics analyses reveal a critical role of selenium in controlling T cell differentiation in Crohn's disease.

Inflammatory bowel disease (IBD) mainly includes Crohn's disease (CD) and ulcerative colitis (UC). Immune disorders play an essential role in the pathogenesis of these two IBDs, but the differences in the immune microenvironment of the colon and their underlying mechanisms remain poorly investigated. Here we examined the immunological features and metabolic microenvironment of untreated individuals with IBD by multiomics analyses. Modulation of CD-specific metabolites, particularly reduced selenium, can obviously shape type 1 T helper (Th1) cell differentiation, which is specifically enriched in CD. Selenium supplementation suppressed the symptoms and onset of CD and Th1 cell differentiation via selenoprotein W (SELW)-mediated cellular reactive oxygen species scavenging. SELW promoted purine salvage pathways and inhibited one-carbon metabolism by recruiting an E3 ubiquitin ligase, tripartite motif-containing protein 21, which controlled the stability of serine hydroxymethyltransferase 2. Our work highlights selenium as an essential regulator of T cell responses and potential therapeutic targets in CD.

Virus-derived circular RNAs populate hepatitis C virus-infected cells.

It is known that pre-mRNAs in eukaryotic cells can be processed to circular RNAs by a backsplicing mechanism. Circular RNAs have great stability and can sequester proteins or small RNAs to exert functions on cellular pathways. Because viruses often exploit host pathways, we explored whether the RNA genome of the cytoplasmic hepatitis C virus is processed to yield virus-derived circRNAs (vcircRNAs). Computational analyses of RNA-seq experiments predicted that the viral RNA genome is fragmented to generate hundreds of vcircRNAs. More than a dozen of them were experimentally verified by rolling-circle amplification. VcircRNAs that contained the viral internal ribosome entry site were found to be translated into proteins that displayed proviral functions. Furthermore, two highly abundant, nontranslated vcircRNAs were shown to enhance viral RNA abundance. These findings argue that novel vcircRNA molecules modulate viral amplification in cells infected by a cytoplasmic RNA virus.

XAF1 prevents hyperproduction of type I interferon upon viral infection by targeting IRF7.

Interferon regulatory factor (IRF) 3 and IRF7 are master regulators of type I interferon (IFN-I)-dependent antiviral innate immunity. Upon viral infection, a positive feedback loop is formed, wherein IRF7 promotes further induction of IFN-I in the later stage. Thus, it is critical to maintain a suitably low level of IRF7 to avoid the hyperproduction of IFN-I. In this study, we find that early expression of IFN-I-dependent STAT1 promotes the expression of XAF1 and that XAF1 is associated specifically with IRF7 and inhibits the activity of XIAP. XAF1-knockout and XIAP-transgenic mice display resistance to viral infection, and this resistance is accompanied by increases in IFN-I production and IRF7 stability. Mechanistically, we find that the XAF1-XIAP axis controls the activity of KLHL22, an adaptor of the BTB-CUL3-RBX1 E3 ligase complex through a ubiquitin-dependent pathway. CUL3-KLHL22 directly targets IRF7 and catalyzes its K48-linked ubiquitination and proteasomal degradation. These findings reveal unexpected functions of the XAF1-XIAP axis and KLHL22 in the regulation of IRF7 stability and highlight an important target for antiviral innate immunity.

All-SnTe-Based Thermoelectric Power Generation Enabled by Stepwise Optimization of n-Type SnTe.

The practical application of thermoelectric devices requires both high-performance n-type and p-type materials of the same system to avoid possible mismatches and improve device reliability. Currently, environmentally friendly SnTe thermoelectrics have witnessed extensive efforts to develop promising p-type transport, making it rather urgent to investigate the n-type counterparts with comparable performance. Herein, we develop a stepwise optimization strategy for improving the transport properties of n-type SnTe. First, we improve the n-type dopability of SnTe by PbSe alloying to narrow the band gap and obtain n-type transport in SnTe with halogen doping over the whole temperature range. Then, we introduce additional Pb atoms to compensate for the cationic vacancies in the SnTe-PbSe matrix, further enhancing the electron carrier concentration and electrical performance. Resultantly, the high-ranged thermoelectric performance of n-type SnTe is substantially optimized, achieving a peak ZT of ∼0.75 at 573 K with a high average ZT (ZTave) exceeding 0.5 from 300 to 823 K in the (SnTe0.98I0.02)0.6(Pb1.06Se)0.4 sample. Moreover, based on the performance optimization on n-type SnTe, for the first time, we fabricate an all-SnTe-based seven-pair thermoelectric device. This device can produce a maximum output power of ∼0.2 W and a conversion efficiency of ∼2.7% under a temperature difference of 350 K, demonstrating an important breakthrough for all-SnTe-based thermoelectric devices. Our research further illustrates the effectiveness and application potential of the environmentally friendly SnTe thermoelectrics for mid-temperature power generation.

High Carrier Mobility and Promising Thermoelectric Module Performance of N-Type PbSe Crystals.

The scarcity of Te hampers the widespread use of Bi2Te3-based thermoelectric modules. Here, the thermoelectric module potential of PbSe is investigated by improving its carrier mobility. Initially, large PbSe crystals are grown with the temperature gradient method to mitigate grain boundary effects on carrier transport. Subsequently, light doping with <1mole‰ halogens (Cl/Br/I) increases room-temperature carrier mobility to ~1600 cm2 V-1 s-1, achieved by reducing carrier concentration compared to traditional heavy doping. Crystal growth design and light doping enhance carrier mobility without affecting effective mass, resulting in a high power factor ~40 µW cm-1 K-2 in PbSe-Cl/Br/I crystals at 300 K. Additionally, Cl/Br/I doping reduces thermal conductivity and bipolar diffusion, leading to significantly lower thermal conductivity at high temperature. Enhanced carrier mobility and suppressed bipolar effect boost ZT values across the entire temperature range in n-type PbSe-Cl/Br/I crystals. Specifically, ZT values of PbSe-Br crystal reach ~0.6 at 300 K, ~1.2 at 773 K, and the average ZT (ZTave) reaches ~1.0 at 300-773 K. Ultimately, ~5.8% power generation efficiency in a PbSe single leg with a maximum temperature cooling difference of 40 K with 7-pair modules is achieved. These results indicate the potential for cost-effective and high-performance thermoelectric cooling modules based on PbSe.

The interplay between autophagy and ferroptosis presents a novel conceptual therapeutic framework for neuroendocrine prostate cancer.

In American men, the incidence of prostate cancer (PC) is the highest among all types of cancer, making it the second leading cause of mortality associated with cancer. For advanced or metastatic PC, antiandrogen therapies are standard treatment options. The administration of these treatments unfortunately carries the potential risk of inducing neuroendocrine prostate cancer (NEPC). Neuroendocrine differentiation (NED) serves as a crucial indicator of prostate cancer development, encompassing various factors such as phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin (PI3K/AKT/mTOR), Yes-associated protein 1 (YAP1), AMP-activated protein kinase (AMPK), miRNA. The processes of autophagy and ferroptosis (an iron-dependent form of programmed cell death) play pivotal roles in the regulation of various types of cancers. Clinical trials and preclinical investigations have been conducted on many signaling pathways during the development of NEPC, with the deepening of research, autophagy and ferroptosis appear to be the potential target for regulating NEPC. Due to the dual nature of autophagy and ferroptosis in cancer, gaining a deeper understanding of the developmental programs associated with achieving autophagy and ferroptosis may enhance risk stratification and treatment efficacy for patients with NEPC.

EGR1 transcriptionally regulates SVEP1 to promote proliferation and migration in human coronary artery smooth muscle cells.

A low-frequency variant of sushi, von Willebrand factor type A, EGF, and pentraxin domain-containing protein 1 (SVEP1) is associated with the risk of coronary artery disease, as determined by a genome-wide association study. SVEP1 induces vascular smooth muscle cell proliferation and an inflammatory phenotype to promote atherosclerosis. In the present study, qRT‒PCR demonstrated that the mRNA expression of SVEP1 was significantly increased in atherosclerotic plaques compared to normal tissues. Bioinformatics revealed that EGR1 was a transcription factor for SVEP1. The results of the luciferase reporter assay, siRNA interference or overexpression assay, mutational analysis and ChIP confirmed that EGR1 positively regulated the transcriptional activity of SVEP1 by directly binding to its promoter. EGR1 promoted human coronary artery smooth muscle cell (HCASMC) proliferation and migration via SVEP1 in response to oxidized low-density lipoprotein (ox-LDL) treatment. Moreover, the expression level of EGR1 was increased in atherosclerotic plaques and showed a strong linear correlation with the expression of SVEP1. Our findings indicated that EGR1 binding to the promoter region drive SVEP1 transcription to promote HCASMC proliferation and migration.

Differences of clinical phenotype between familial and sporadic Crohn's disease in East China.

PURPOSE: Family history is one of the strongest risk factors for inflammatory bowel diseases (IBD) while studies about the clinical phenotype of familial IBD are limited. This study aimed to compare the phenotypic features of familial Crohn's disease (CD) with sporadic CD. METHODS: Familial CD was defined as CD patients having one or more first, second, third, fourth degree, or above relatives with CD. Sporadic CD patients hospitalized during the same period were matched 1:3 by age and gender. Differences in clinical characteristics, phenotype distribution, extraintestinal manifestations, and complications at diagnosis, as well as treatment regimen and surgery, were compared between familial and sporadic CD. RESULTS: The familial CD was associated with a higher rate of past appendectomy history (P = 0.009), more intestinal perforation at onset (P = 0.012), more MRI results of anal lesion (P = 0.023), and gastrointestinal perforation (P = 0.040) at diagnosis, higher rate of past intestinal surgery history (P = 0.007), more number of intestinal surgeries (P = 0.037), longer duration of follow-up (P = 0.017), lower rate of taking biologicals for current maintenance (P = 0.043), lower tendency to upgrade to biologicals during follow-up (P = 0.013), higher possibility to experience gastrointestinal obstruction (P = 0.047), and abdominal abscess during follow-up (P = 0.045). CONCLUSION: Familial CD is associated with a more aggressive clinical phenotype.

Efficacy and safety of risankizumab for Crohn's disease in patients from Asian countries: a post hoc subanalysis of the global phase 3 ADVANCE, MOTIVATE, and FORTIFY studies.

BACKGROUND AND AIM: The anti-interleukin-23 antibody risankizumab is being investigated as a treatment for moderate-to-severe Crohn's disease. This post hoc subanalysis evaluates the efficacy and safety of risankizumab therapy in Asian patients. METHODS: ADVANCE (NCT03105128) and MOTIVATE (NCT03104413) were randomized, double-blind, placebo-controlled, phase 3 induction studies. Patients with intolerance/inadequate response to biologic (MOTIVATE) and/or conventional therapy (ADVANCE) were randomized to receive intravenous risankizumab (600 or 1200 mg) or placebo at weeks 0, 4, and 8. Clinical responders to risankizumab could enter the phase 3, randomized, double-blind, placebo-controlled maintenance withdrawal study (FORTIFY; NCT03105102). Patients were rerandomized to receive subcutaneous risankizumab (180 or 360 mg) or placebo (withdrawal) every 8 weeks for 52 weeks. RESULTS: Among 198 Asian patients in the induction studies, clinical remission and endoscopic response at week 12 were achieved by 61.4% and 40.0%, 59.5% and 35.8%, and 27.3% and 9.1% of patients in the risankizumab 600 mg, risankizumab 1200 mg, and placebo groups, respectively. Among 67 patients who entered the maintenance study, clinical remission and endoscopic response at week 52 were achieved by 57.1% and 52.4%, 75.0% and 40.0%, and 53.8% and 34.6% of patients in the risankizumab 180 mg, risankizumab 360 mg, and placebo (withdrawal) groups, respectively. Fistula closure was observed with risankizumab treatment in 28.6% (induction) and 57.1% (maintenance) of patients. Efficacy trends and safety profile were similar to those in non-Asian patients. CONCLUSION: Consistent with non-Asian and global population results, risankizumab was effective and well tolerated in Asian patients with Crohn's disease.

Epithelial CRL4DCAF2 Is Critical for Maintaining Intestinal Homeostasis Against DSS-Induced Colitis by Regulating the Proliferation and Repair of Intestinal Epithelial Cells.

BACKGROUND AND AIMS: Inflammatory bowel disease (IBD) is currently gaining an increasing global interest. Intestinal epithelial barrier dysfunction is crucial toward developing IBD; however, the underlying mechanisms are not yet elucidated. This study is aimed at elucidating the function of CRL4DCAF2, an E3 ligase, toward mediating intestinal homeostasis. METHODS: Colon samples were collected from patients with IBD and healthy individuals to examine the expression of CRL4DCAF2. CRL4DCAF2 conditional knockdown in mouse intestinal epithelial cells (IECs) (DCAF2EKD) were constructed. DCAF2EKD and their littermate control (DCAF2EWT) were treated with dextran sodium sulfate (DSS) to induce acute colitis. Transcriptome analysis was performed on inflamed colon samples obtained from the mice. Cell cycle regulators were evaluated using real-time polymerase chain reaction (PCR), while tight junction and apoptosis proteins were examined via immunofluorescence and western blot. RESULTS: CRL4DCAF2 expression was significantly decreased in the inflamed IBD epithelium, and low expression of CRL4DCAF2 associated with high recurrence risk. Mice with DCAF2 specific knockout in IECs suffer from embryonic death. Multiple genes involved in cell proliferation, immune response, and gap junction were differentially expressed in inflamed colon from DCAF2EKD compared with DCAF2EWT. Furthermore, conditional downregulation of CRL4DCAF2 in the intestinal epithelium induced primarily epithelial damage, increased intestinal permeability, and diminished tight junction protein expression. In vivo and in vitro cell transfection experiments revealed that CRL4DCAF2 enhanced cell proliferation by promoting p21 ubiquitination and degradation, thereby inhibiting G2/M cell cycle. In addition, CRL4DCAF2 can also inhibit IEC apoptosis and promote cell autophagy. CONCLUSIONS: CRL4DCAF2 downregulation in IECs promotes intestinal barrier dysfunction and inhibits IEC proliferation, thus making it more susceptible to inflammation.

The effect of different pterygium surgery techniques on the ocular surface parameters in different durations: a systematic review and meta-analysis.

PURPOSE: To evaluate the effects of different pterygium surgery techniques on ocular surface (OS) in different follow-up periods. METHODS: PubMed, Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wan Fang, and China Biology Medicine disc were searched for studies reporting pre- and post-operative OS parameters in pterygium. RESULTS: A total of 33 articles were finally included. Three OS parameters showed relatively consistent changing trends after surgery including ocular surface disease index (OSDI), tear film break-up time (BUT), and score of corneal fluorescein staining (SCFS). They worsened significantly at 1w post-operation and then gradually improved: OSDI and BUT showed obvious improvement in 1 m post-operation (SMD = - 0.58, 95%CI = [- 1.04, - 0.13]; SMD = 0.42, 95%CI = [0.06, 0.78]); SCFS was restored to preoperative levels in 3 m after surgery (SMD = - 0.54, 95%CI = [- 1.16, 0.07]). Another parameter, Schirmer test without anesthesia (SIT), presented transient increase at 1w post-operation (SMD = 0.87, 95%CI = [0.27, 1.47]) and presented a relatively stable improvement after 1 m post-operation (SMD = 0.52, 95%CI = [0.16, 0.89]). All parameters in amniotic membrane graft (AMT) showed better improvement in early stage and they showed non-inferior improvements in the long term compared with conjunctival autograft (CAG). Limbal-conjunctival autograft (LCAG) made excellent improvement to OS in the long term while pterygium excision (PE) showed the worst OS. The type of pterygium (primary and secondary), diabetes mellitus (DM) status, and fixation method had certain effects on the results. CONCLUSIONS: OS of pterygium is deteriorated at 1w post-operation then gradually improved to preoperative levels after 1 m post-operation. Among various surgery techniques, LCAG had the best improvement to OS which especially displayed in the long-term outcomes.

Limited value of platelet-related markers in diagnosing periprosthetic joint infection.

OBJECTIVE: To evaluate the diagnostic values of serum platelet count (PC), mean platelet volume ratio (MPV), platelet count to mean platelet volume ratio (PVR), platelet to lymphocyte ratio (PLR), platelet to neutrophil ratio (PNR), PC/Albumin-globulin ratio (PC/AGR), and PC/C-reactive protein (PC/ CRP) in the diagnosis of periprosthetic joint infection (PJI). METHODS: The medical records were retrospectively analyzed of the 158 patients who had undergone hip or knee revisions from January 2018 to May 2022. Of them, 79 cases were diagnosed with PJI and 79 with aseptic loosening (AL). PJI was defined using the Musculoskeletal Infection Society criteria. The plasma levels of CRP, the erythrocyte sedimentation rate (ESR), PC, MPV, PVR, PLR, PNR, PC/AGR, and PC/CRP in the 2 groups were recorded and analyzed. In addition, tests were performed according to different joint types. The receiver operating characteristic curve was used to calculate the sensitivity and specificity of each indicator. The diagnostic value for each indicator was calculated according to the area under the curve (AUC). RESULTS: The PC, PVR, PLR and PC/AGR levels in the PJI group were significantly higher than those in the AL group, while PC/CRP levels were significantly lower (P < 0.001). The AUC for PC/CRP, and PC/AGR was 0.804 and 0.802, respectively, which were slightly lower than that of CRP (0.826) and ESR (0.846). ROC analysis for PC/CRP, and PC/AGR revealed a cut-off value of 37.80 and 160.63, respectively, which provided a sensitivity of 73.42% and 84.81% and a specificity of 75.95% and 65.82% for PJI. The area under the curve of PLR and PC was 0.738 and 0.702. The area under the curve values for PVR, PNR, and MPV were 0.672, 0.553, and 0.544, respectively. CONCLUSIONS: The results of this study suggest that PC, PLR, PC/CRP, and PC/AGR values do not offer significant advantages over ESR or CRP values when employed for the diagnosis of PJI. PVR, PNR, and MPV were not reliable in the diagnosis of PJI.

Astrocytic CXCL5 hinders microglial phagocytosis of myelin debris and aggravates white matter injury in chronic cerebral ischemia.

BACKGROUND: Chronic cerebral ischemia induces white matter injury (WMI) contributing to cognitive decline. Both astrocytes and microglia play vital roles in the demyelination and remyelination processes, but the underlying mechanism remains unclear. This study aimed to explore the influence of the chemokine CXCL5 on WMI and cognitive decline in chronic cerebral ischemia and the underlying mechanism. METHODS: Bilateral carotid artery stenosis (BCAS) model was constructed to mimic chronic cerebral ischemia in 7-10 weeks old male mice. Astrocytic Cxcl5 conditional knockout (cKO) mice were constructed and mice with Cxcl5 overexpressing in astrocytes were generated by stereotactic injection of adeno-associated virus (AAV). WMI was evaluated by magnetic resonance imaging (MRI), electron microscopy, histological staining and western blotting. Cognitive function was examined by a series of neurobehavioral tests. The proliferation and differentiation of oligodendrocyte progenitor cells (OPCs), phagocytosis of microglia were analyzed via immunofluorescence staining, western blotting or flow cytometry. RESULTS: CXCL5 was significantly elevated in the corpus callosum (CC) and serum in BCAS model, mainly expressed in astrocytes, and Cxcl5 cKO mice displayed improved WMI and cognitive performance. Recombinant CXCL5 (rCXCL5) had no direct effect on the proliferation and differentiation of OPCs in vitro. Astrocytic specific Cxcl5 overexpression aggravated WMI and cognitive decline induced by chronic cerebral ischemia, while microglia depletion counteracted this effect. Recombinant CXCL5 remarkably hindered microglial phagocytosis of myelin debris, which was rescued by inhibition of CXCL5 receptor C-X-C motif chemokine receptor 2 (CXCR2). CONCLUSION: Our study revealed that astrocyte-derived CXCL5 aggravated WMI and cognitive decline by inhibiting microglial phagocytosis of myelin debris, suggesting a novel astrocyte-microglia circuit mediated by CXCL5-CXCR2 signaling in chronic cerebral ischemia.

A novel plasma proteomic-based model for predicting liver fibrosis in HIV/HBV co-infected adults.

To establish a plasma model to predict the risk of liver fibrosis in HIV/HBV co-infected individuals. Quantitative liquid chromatography-tandem mass spectrometry(LC-MS/MS) was used to identify differentially expressed proteins (DEPs) in plasma collected from HIV/HBV co-infected individuals with and without liver fibrosis. In total, 97 DEPs were identified, among which 11 were further validated as potential biomarkers, with immunoglobulin and complement components being the most common proteins. These markedly altered proteins were found to mediate pathophysiological pathways, including humoral immune response, complement and coagulation cascades, and complement activation. A visual logistic model, in which immunoglobulin heavy variable 3-20 (IGHV3-20), immunoglobulin heavy variable 1-24 (IGHV1-24), and macrophage colony-stimulating factor 1 receptor (CSF1R) proteins were included, has been established to predict liver fibrosis in HIV/HBV co-infected individuals. The preliminary conclusion showed that the combination of IGHV3-20, IGFHV1-24, and CSF1R is expected to become a predictive model for liver fibrosis in the context of HIV/HBV co-infection and a further validation should be performed.

Rhein protects retinal Müller cells from high glucose-induced injury via activating the AMPK/Sirt1/PGC-1α pathway.

Oxidative stress, inflammation and apoptosis are important pathogenic factors of diabetic retinopathy (DR). In the current study, we aimed to evaluate the potential role of Rhein, a natural anthraquinone compound found in rhubarb, in high glucose (HG)-induced Müller cells (MIO-M1). Cell Counting Kit­8 assay, TUNEL assay, Western blot analysis, Reverse transcription quantitative polymerase chain reaction (RT-qPCR), and ELISA were conducted to assess the effects of Rhein on Müller cells. Additionally, the EX-527, an Sirt1 inhibitor, was used to study whether the effects of Rhein, on HG-induced Müller cells were mediated by activation of the Sirt1 signaling pathway. Our data showed that Rhein improved cell viability of HG-induced Müller cells. Rhein reduced the ROS and MDA production and increased the activities of SOD and CAT in Müller cells in response to HG stimulation. Rhein decreased the production of VEGF, IL-1ß, IL-6 and TNF-α. Moreover, Rhein attenuated HG-induced apoptosis, evidenced by increase in Bcl-2 level and decreases in the Bax, caspase-3 expression. It was also found that EX-527 counteracted Rhein-mediated anti-inflammatory, antioxidant and anti-apoptosis effects on Müller cells. The protein levels of p-AMPK and PGC-1α were also upregulated by Rhein. In conclusion, these findings support that Rhein may ameliorate HG-induced inflammation, oxidative stress, apoptosis and protect against mitochondrial dysfunction by the activation of the AMPK/Sirt1/PGC-1α signaling pathway.

Ultrasensitive Atomic Comagnetometer with Enhanced Nuclear Spin Coherence.

Achieving high energy resolution in spin systems is important for fundamental physics research and precision measurements, with alkali-noble-gas comagnetometers being among the best available sensors. We found a new relaxation mechanism in such devices, the gradient of the Fermi-contact-interaction field that dominates the relaxation of hyperpolarized nuclear spins. We report on precise control over spin distribution, demonstrating a tenfold increase of nuclear spin hyperpolarization and transverse coherence time with optimal hybrid optical pumping. Operating in the self-compensation regime, our ^{21}Ne-Rb-K comagnetometer achieves an ultrahigh inertial rotation sensitivity of 3×10^{-8} rad/s/Hz^{1/2} in the frequency range from 0.2 to 1.0 Hz, which is equivalent to the energy resolution of 3.1×10^{-23} eV/Hz^{1/2}. We propose to use this comagnetometer to search for exotic spin-dependent interactions involving proton and neutron spins. The projected sensitivity surpasses the previous experimental and astrophysical limits by more than 4 orders of magnitude.

Temporal trends in surgery for Crohn's disease: a ten-year single-center retrospective study.

PURPOSE: Crohn's disease (CD) is a chronic inflammatory bowel disease that requires surgery in many cases. The aim of this article is to present the experience of a referral center regarding surgical interventions for CD, while also exploring the transformations that have occurred over 10 years. METHODS: The data of patients underwent abdominal surgery for CD between 2013 and 2022 were collected prospectively. Data were compared between two periods (2013-2017 and 2018-2022). Temporal trends were assessed with the Mann-Kendall trend test. RESULTS: A total of 1059 individuals underwent 1176 surgical procedures, of which 67.1% were male. The median age of patients at the time of surgery was 36.0 years, and an overall increasing trend was observed in surgical volume (z = 3.04; p = 0.002). The proportion of patients treated with biologics increased from the first period (2013-2017) to the second (2018-2022), rising from 19.2% to 33.5% (p < 0.001). In the second stage, the proportion of patients who underwent surgery for abscesses or fistulas increased (47.8% vs. 40.0%, p = 0.028), while the percentage of emergency surgeries declined (3.0% vs. 7.1%, p = 0.001). Furthermore, there was a rise in the proportion of laparoscopic surgeries (76.5% vs. 63.7%, p < 0.001), coupled with a decrease in stoma rates (15.4% vs. 30.5%, p < 0.001) and postoperative complications (23.0% vs. 30.5%, p = 0.007). CONCLUSION: The frequency of biologics use in CD surgery have increased over time, and the proportion of penetrating patients has grown. Minimally invasive surgical methods have become the norm, and surgical outcomes have markedly enhanced, evidenced by a substantial reduction in both stoma rates and complication rates.

Phenome-wide association study and precision medicine of cardiovascular diseases in the post-COVID-19 era.

SARS-CoV-2 infection causes injuries of not only the lungs but also the heart and endothelial cells in vasculature of multiple organs, and induces systemic inflammation and immune over-reactions, which makes COVID-19 a disease phenome that simultaneously affects multiple systems. Cardiovascular diseases (CVD) are intrinsic risk and causative factors for severe COVID-19 comorbidities and death. The wide-spread infection and reinfection of SARS-CoV-2 variants and the long-COVID may become a new common threat to human health and propose unprecedented impact on the risk factors, pathophysiology, and pharmacology of many diseases including CVD for a long time. COVID-19 has highlighted the urgent demand for precision medicine which needs new knowledge network to innovate disease taxonomy for more precise diagnosis, therapy, and prevention of disease. A deeper understanding of CVD in the setting of COVID-19 phenome requires a paradigm shift from the current phenotypic study that focuses on the virus or individual symptoms to phenomics of COVID-19 that addresses the inter-connectedness of clinical phenotypes, i.e., clinical phenome. Here, we summarize the CVD manifestations in the full clinical spectrum of COVID-19, and the phenome-wide association study of CVD interrelated to COVID-19. We discuss the underlying biology for CVD in the COVID-19 phenome and the concept of precision medicine with new phenomic taxonomy that addresses the overall pathophysiological responses of the body to the SARS-CoV-2 infection. We also briefly discuss the unique taxonomy of disease as Zheng-hou patterns in traditional Chinese medicine, and their potential implications in precision medicine of CVD in the post-COVID-19 era.

Electroacupuncture Enhances Gastric Accommodation via the Autonomic and Cytokine Mechanisms in Functional Dyspepsia.

BACKGROUND: Due to complex pathophysiology of functional dyspepsia, medications to treat functional dyspepsia are not effective for all patients. Transcutaneous electrical acustimulation (TEA) is an potentially effective therapy for functional dyspepsia without proofs of definite mechanisms. AIMS: We aimed to investigate the therapeutic impacts of TEA on postprandial distress syndrome (PDS) and explore potential neuroimmune mechanisms. METHODS: We conducted a double-blinded, randomized, controlled trial in 30 PDS patients randomized for 4-week TEA or sham-TEA. Dyspeptic symptoms, gastric accommodation, gastric emptying and heart rate variability (HRV) were assessed. Duodenal mucosal inflammation was also evaluated. RESULTS: The dyspeptic symptoms were improved with TEA compared with sham-TEA (P = 0.03). The initial satiety volume and the maximum tolerable volume (MTV) were both improved after the TEA treatment, compared with the sham-TEA group (P all < 0.05). The gastric emptying time (T1/2) was not altered with TEA or sham-TEA. The TEA treatment increased vagal activity and decreased sympathovagal ratio assessed by HRV (P all < 0.01). The IL-6 expression in bulb mucosa was downregulated by the TEA treatment compared to the baseline (P < 0.05). CONCLUSIONS: Noninvasive TEA improves gastric accommodation and dyspeptic symptoms, possibly by downregulating the IL-6 expression in duodenal bulb mucosa via the vagal efferent pathway.