Microbiome-driven anticancer therapy: A step forward from natural products.

Human microbiomes, considered as a new emerging and enabling cancer hallmark, are increasingly recognized as critical effectors in cancer development and progression. Manipulation of microbiome revitalizing anticancer therapy from natural products shows promise toward improving cancer outcomes. Herein, we summarize our current understanding of the human microbiome-driven molecular mechanisms impacting cancer progression and anticancer therapy. We highlight the potential translational and clinical implications of natural products for cancer prevention and treatment by developing targeted therapeutic strategies as adjuvants for chemotherapy and immunotherapy against tumorigenesis. The challenges and opportunities for future investigations using modulation of the microbiome for cancer treatment are further discussed in this review.

"Nutrient-fungi-host" tripartite interaction in cancer progression.

The human microbiome exhibits a profound connection with the cancer development, progression, and therapeutic response, with particular emphasis on its components of the mycobiome, which are still in the early stages of research. In this review, we comprehensively summarize cancer-related symbiotic and pathogenic fungal genera. The intricate mechanisms through which fungi impact cancer as an integral member of both gut and tissue-resident microbiomes are further discussed. In addition, we shed light on the pivotal physiological roles of various nutrients, including cholesterol, carbohydrates, proteins and minerals, in facilitating the growth, reproduction, and invasive pathogenesis of the fungi. While our exploration of the interplay between nutrients and cancer, mediated by the mycobiome, is ongoing, the current findings have yet to yield conclusive results. Thus, delving into the relationship between nutrients and fungal pathogenesis in cancer development and progression would provide valuable insights into anticancer therapy and foster precision nutrition and individualized treatments that target fungi from bench to bedside.

USP14 deficiency inhibits neointima formation following vascular injury via degradation of Skp2 protein.

Ubiquitin-proteasome system (UPS) is involved in vascular smooth muscle cell (VSMC) proliferation. Deubiquitinating enzymes (DUBs) have an essential role in the UPS-regulated stability of the substrate; however, the function of DUBs in intimal hyperplasia remains unclear. We screened DUBs to identify a protein responsible for regulating VSMC proliferation and identified USP14 protein that mediates cancer development, inflammation, and foam cell formation. USP14 promotes human aortic smooth muscle cell and A7r5 cell growth in vitro, and its inhibition or deficiency decreases the intimal area in the mice carotid artery ligation model. In addition, USP14 stabilizes Skp2 expression by decreasing its degradation, while Skp2 overexpression rescues USP14 loss-induced issues. The current findings suggested an essential role of USP14 in the pathology of vascular remodeling, deeming it a promising target for arterial restenosis therapy.

PRM1201 effectively inhibits colorectal cancer metastasis via shaping gut microbiota and short- chain fatty acids.

BACKGROUND: PRM1201 is a traditional medicine with beneficial effects against colorectal cancer (CRC) metastasis. However, the underlying mechanism of this action remains to be determined. HYPOTHESIS: Remodeling microbiota and short-chain fatty acids (SCFAs) metabolism might be a potential mechanism to explain the anti-metastatic action of PRM1201, as this gut-microbiota dependent effect involves downregulation of histone deacetylation and EMT. METHODS: To investigate this possibility, clinical specimens were sequenced and the correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFA-producing bacteria was studied. To obtain solid causal evidence, a mouse metastasis model was established to detect the influence of PRM1201 on cancer metastasis. Specifically, 16S amplicon sequencing, ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) analysis, and bacterial manipulation were used to examine the gut microbiota-driven anti-metastatic action of PRM1201. RESULTS: Clinical data showed that PRM1201 increased both the number of SCFA-producing bacteria and generation of SCFAs in the feces of CRC patients. A positive correlation between the anti-metastatic efficacy of PRM1201 and the restoration of SCFAs observed. The animal experiments demonstrated that PRM1201 effectively blocked CRC metastasis in a dose-dependent manner. PRM1201 treatment modulated the composition of gut microbiota, and promoted the proliferation of beneficial SCFAs producers such as Akkermansia, Lachnospiraceae_NK4A136_group and Blautia, while simultaneously reducing the abundance of pathogenic bacteria like Escherichia-Shigella. In addition, PRM1201 led to augmentation of SCFAs content. Further results indicated that the anti-cancer metastatic mechanism of PRM1201 was linked to inhibition of histone deacetylation and suppression of epithelial-to-mesenchymal transition (EMT) in metastatic lesions. Microbiota depletion treatment and fecal microbiota transplantation (FMT) underscored the microbiota-dependent nature of this phenomenon. Moreover, this anti-colorectal cancer metastatic effect and mechanism of total SCFAs and single SCFA were also confirmed. CONCLUSION: In summary, PRM1201 exerts its anti-metastatic effects by modulating SCFA-producing bacteria and enhancing the production of SCFAs. Furthermore, the prebiotic-like actions of PRM1201, along with the PRM1201-treated bacteria, function as inhibitors of histone deacetylases (DHACs) thereby effectively suppressing EMT events.

Reactive P and S co-doped porous hollow nanotube arrays for high performance chloride ion storage.

Developing stable, high-performance chloride-ion storage electrodes is essential for energy storage and water purification application. Herein, a P, S co-doped porous hollow nanotube array, with a free ion diffusion pathway and highly active adsorption sites, on carbon felt electrodes (CoNiPS@CF) is reported. Due to the porous hollow nanotube structure and synergistic effect of P, S co-doped, the CoNiPS@CF based capacitive deionization (CDI) system exhibits high desalination capacity (76.1 mgCl- g-1), fast desalination rate (6.33 mgCl- g-1 min-1) and good cycling stability (capacity retention rate of > 90%), which compares favorably to the state-of-the-art electrodes. The porous hollow nanotube structure enables fast ion diffusion kinetics due to the swift ion transport inside the electrode and the presence of a large number of reactive sites. The introduction of S element also reduces the passivation layer on the surface of CoNiP and lowers the adsorption energy for Cl- capture, thereby improving the electrode conductivity and surface electrochemical activity, and further accelerating the adsorption kinetics. Our results offer a powerful strategy to improve the reactivity and stability of transition metal phosphides for chloride capture, and to improve the efficiency of electrochemical dechlorination technologies.

MicroRNA-206 as a potential cholesterol-lowering drug is superior to statins in mice.

Hypercholesterolemia is frequently intertwined with hepatosteatosis, hypertriglyceridemia, and hyperglycemia. This study is designed to assess the therapeutic efficacy of miR-206 in contrast to statins in the context of managing hypercholesterolemia in mice. We previously showed that miR-206 is a potent inhibitor of de novo lipogenesis (DNL), cholesterol synthesis, and gluconeogenesis in mice. Given that these processes occur within hepatocytes, we employed a mini-circle (MC) system to deliver miR-206 specifically to hepatocytes (designated as MC-miR-206). A single intravenous injection of MC-miR-206 maintained high levels of miR-206 in the liver for at least two weeks, thereby maintaining suppression of hepatic DNL, cholesterol synthesis, and gluconeogenesis. MC-miR-206 significantly reduced DNA damage, endoplasmic reticulum and oxidative stress, and hepatic toxicity. Therapeutically, both MC-miR-206 and statins significantly reduced total serum cholesterol and triglycerides as well as LDL cholesterol and VLDL cholesterol in mice maintained on the normal chow and high-fat high-cholesterol diet. MC-miR-206 reduced liver weight, hepatic triglycerides and cholesterol, and blood glucose, while statins slightly increased hepatic cholesterol and blood glucose and failed to affect levels of liver weight and hepatic triglycerides. Mechanistically, miR-206 alleviated hypercholesterolemia by inhibiting hepatic cholesterol synthesis, while statins increased HMGCR activity, hepatic cholesterol synthesis, and fecal-neutral steroid excretion. MiR-206 facilitates the regression of hypercholesterolemia, hypertriglyceridemia, hyperglycemia, and hepatosteatosis. MiR-206 outperforms statins by reducing hyperglycemia, hepatic cholesterol levels, and hepatic toxicity.

The vacuolar fusion regulated by HOPS complex promotes hyphal initiation and penetration in Candida albicans.

The transition between yeast and hyphae is crucial for regulating the commensalism and pathogenicity in Candida albicans. The mechanisms that affect the invasion of hyphae in solid media, whose deficiency is more related to the pathogenicity of C. albicans, have not been elucidated. Here, we found that the disruption of VAM6 or VPS41 which are components of the homotypic vacuolar fusion and protein sorting (HOPS) complex, or the Rab GTPase YPT72, all responsible for vacuole fusion, led to defects in hyphal growth in both liquid and solid media, but more pronounced on solid agar. The phenotypes of vac8Δ/Δ and GTR1OE-vam6Δ/Δ mutants indicated that these deficiencies are mainly caused by the reduced mechanical forces that drive agar and organs penetration, and confirmed that large vacuoles are required for hyphal mechanical penetration. In summary, our study revealed that large vacuoles generated by vacuolar fusion support hyphal penetration and provided a perspective to refocus attention on the role of solid agar in evaluating C. albicans invasion.

Modified Banxiaxiexin decoction benefitted chemotherapy in treating gastric cancer by regulating multiple targets and pathways.

ETHNOPHARMACOLOGICAL RELEVANCE: Chemotherapy tolerance weakened efficacy of chemotherapy drugs in the treating gastric cancer (GC). Banxiaxiexin decoction (BXXXD) was widely used in digestive diseases for thousands of years in Traditional Chinese medicine (TCM). In order to better treat GC, three other herbs were added to BXXXD to create a new prescription named Modified Banxiaxiexin decoction (MBXXXD). Although MBXXXD potentially treated GC by improving chemotherapy tolerance, the possible mechanisms were still unknown. AIM OF THE STUDY: To explore the therapeutic effect of MBXXXD on GC patients and explore the possible anti-cancer mechanism. MATERIALS AND METHODS: A randomized controlled trial (n = 146) was conducted to evaluate the clinical efficacy between MBXXXD + chemotherapy (n = 73) and placebo + chemotherapy (n = 73) in GC patients by testing overall survival, progression free survival, clinical symptoms, quality of life score, tumor markers, T cell subpopulation, and adverse reactions. Network pharmacology was conducted to discover the potential mechanism of MBXXXD in treating GC. Metabolic activity assay, cell clone colony formation and mitochondrial apoptosis were detected in human GC cell lines including AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD. Multiple pathways including P53, AKT, IκB, P65, P38, ERK, JNK p-AKT, p-P65, p-P38, p-ERK and p-JNK in AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy were also detected. RESULTS: MBXXXD + chemotherapy promoted overall survival and progression free survival, improved clinical symptoms and quality of life score, increased T4 lymphocyte ratio and T8 lymphocyte ratio as well as T4/T8 lymphocyte ratio, and alleviated adverse reactions in GC patients. Network pharmacology predicted multiple targets and pathways of MBXXXD in treating GC including apoptosis, P53 pathway, AKT pathway, MAPK pathway. MBXXXD inhibited cell viability, decreased cell clone colony formation, and promoted mitochondrial apoptosis by producing reactive oxygen species (ROS), promoting mitochondrial permeability transition pore (MPTP) and the cleavage of pro-caspase-3 and pro-caspase-9, and decreasing mito-tracker red Chloromethyl-X-rosamine (CMXRos) in AGS cell, KNM-45 cell and SGC7901 cell. MBXXXD up-regulated the expression of P53 and IκB, and down-regulated the expression of p-AKT, p-P65, p-P38, p-ERK, p-JNK, AKT, P65, P38, ERK and JNK AGS cell, KNM-45 cell and SGC7901 cell treated by MBXXXD and GC patients treated by MBXXXD + chemotherapy. CONCLUSION: MBXXXD benefitted chemotherapy for GC by regulating multiple targets and pathways.

Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration.

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1+ macrophages, RGCC+ endothelial cells, ACKR1+ endothelial cells and ADAM12+ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2+ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2+ macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26RtdTomato mice to lethally irradiated Ackr1-/- mice (Ackr1-/- chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2+ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2+ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.

Combining various acupuncture therapies with multimodal analgesia to enhance postoperative pain management following total knee arthroplasty: a network meta-analysis of randomized controlled trials.

Objective: This study aims to evaluate the efficacy and safety of various acupuncture treatments in conjunction with multimodal analgesia (MA) for managing postoperative pain and improving knee function in patients undergoing total knee arthroplasty (TKA), based on the findings from clinical research indicating the potential benefits of acupuncture-related therapies in this context. Methods: We searched Web of Science, PubMed, SCI-hub, Embase, Cochrane Library, China Biology Medicine (CBM), China National Knowledge Infrastructure (CNKI), Wanfang Data, and Chinese Scientific Journal Database (VIP) to collect randomized controlled trials of acupuncture-related therapies for post-TKA pain. After independent screening and data extraction, the quality of the included literature was evaluated. The potential for bias in the studies incorporated in the analysis was assessed according to the guidelines outlined in the Cochrane Handbook 5.1. Network meta-analysis (NMA) was conducted using RevMan 5.4 and Stata 16.0 software, with primary outcome measures including visual analog scale (VAS), pain pressure threshold (PPT), hospital for special surgery knee score (HSS), and knee joint range of motion (ROM). Furthermore, the interventions were ranked based on the SUCRA value. Results: We conducted an analysis of 41 qualifying studies encompassing 3,003 patients, examining the efficacy of four acupuncture therapies (acupuncture ACU, electroacupuncture EA, transcutaneous electrical acupoint stimulation TEAS, and auricular acupoint therapy AAT) in conjunction with multimodal analgesia (MA) and MA alone. The VAS results showed no significant difference in efficacy among the five interventions for VAS-3 score. However, TEAS+MA (SMD: 0.67; 95%CI: 0.01, 1.32) was more effective than MA alone for VAS-7 score. There was no significant difference in PPT score among the three interventions. ACU + MA (SMD: 6.45; 95%CI: 3.30, 9.60), EA + MA (SMD: 4.89; 95%CI: 1.46, 8.32), and TEAS+MA (SMD: 5.31; 95%CI: 0.85, 9.78) were found to be more effective than MA alone for HSS score. For ROM score, ACU + MA was more efficacious than EA + MA, TEAS+MA, and AAT + MA, MA. Regarding the incidence of postoperative adverse reactions, nausea and vomiting were more prevalent after using only MA. Additionally, the incidence of postoperative dizziness and drowsiness following ACU + MA (OR = 4.98; 95%CI: 1.01, 24.42) was observed to be higher compared to that after AAT + MA intervention. Similarly, the occurrence of dizziness and drowsiness after MA was found to be significantly higher compared to the following interventions: TEAS+MA (OR = 0.36; 95%CI: 0.18, 0.70) and AAT + MA (OR = 0.20; 95%CI: 0.08, 0.50). The SUCRA ranking indicated that ACU + MA, EA + MA, TEAS+MA, and AAT + MA displayed superior SUCRA scores for each outcome index, respectively. Conclusion: For the clinical treatment of post-TKA pain, acupuncture-related therapies can be selected as a complementary and alternative therapy. EA + MA and TEAS+MA demonstrate superior efficacy in alleviating postoperative pain among TKA patients. ACU + MA is the optimal choice for promoting postoperative knee joint function recovery in TKA patients. AAT + MA is recommended for preventing postoperative adverse reactions. Systematic review registration: https://www.crd.york.ac.uk/, identifier (CRD42023492859).

RSPO3 induced by Helicobacter pylori extracts promotes gastric cancer stem cell properties through the GNG7/ß-catenin signaling pathway.

BACKGROUND: Helicobacter pylori (H. pylori) accounts for the majority of gastric cancer (GC) cases globally. The present study found that H. pylori promoted GC stem cell (CSC)-like properties, therefore, the regulatory mechanism of how H. pylori promotes GC stemness was explored. METHODS: Spheroid-formation experiments were performed to explore the self-renewal capacity of GC cells. The expression of R-spondin 3 (RSPO3), Nanog homeobox, organic cation/carnitine transporter-4 (OCT-4), SRY-box transcription factor 2 (SOX-2), CD44, Akt, glycogen synthase kinase-3ß (GSK-3ß), p-Akt, p-GSK-3ß, ß-catenin, and G protein subunit gamma 7 (GNG7) were detected by RT-qPCR, western blotting, immunohistochemistry (IHC), and immunofluorescence. Co-immunoprecipitation (CoIP) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) were performed to identify proteins interacting with RSPO3. Lentivirus-based RNA interference constructed short hairpin (sh)-RSPO3 GC cells. Small interfering RNA transfection was performed to inhibit GNG7. The in vivo mechanism was verified using a tumor peritoneal seeding model in nude mice. RESULTS: H. pylori extracts promoted a CSC-like phenotype in GC cells and elevated the expression of RSPO3. RSPO3 knockdown significantly reduced the CSC-like properties induced by H. pylori. Previous studies have demonstrated that RSPO3 potentiates the Wnt/ß-catenin signaling pathway, but the inhibitor of Wnt cannot diminish the RSPO3-induced activation of ß-catenin. CoIP and LC-MS/MS revealed that GNG7 is one of the transmembrane proteins interacting with RSPO3, and it was confirmed that RSPO3 directly interacted with GNG7. Recombinant RSPO3 protein increased the phosphorylation level of Akt and GSK-3ß, and the expression of ß-catenin in GC cells, but this regulatory effect of RSPO3 could be blocked by GNG7 knockdown. Of note, GNG7 suppression could diminish the promoting effect of RSPO3 to CSC-like properties. In addition, RSPO3 suppression inhibited MKN45 tumor peritoneal seeding in vivo. IHC staining also showed that RSPO3, CD44, OCT-4, and SOX-2 were elevated in H. pylori GC tissues. CONCLUSION: RSPO3 enhanced the stemness of H. pylori extracts-infected GC cells through the GNG7/ß-catenin signaling pathway.

Different acupuncture and moxibustion therapies in the treatment of IBS-D with anxiety and depression: A network meta-analysis.

BACKGROUND: Currently, a variety of Western medical interventions are available for the treatment of diarrhea-predominant irritable bowel syndrome (IBS-D) with comorbid anxiety and depression. However, the attendant negative effects also emerge, putting pressure on healthcare resources and socio-economic structures. In recent years, the benefits of acupuncture (ACU) and moxibustion in the treatment of IBS-D with anxiety and depression have gradually emerged. However, there are many types of ACU-moxibustion-related treatments, and the aim of this study is to examine the effectiveness of different ACU-moxibustion therapies in the treatment of anxiety and depression in IBS-D patients. METHODS: Searched and identified randomized controlled trials (RCTS) of ACU for the treatment of anxiety and depression in patients with irritable bowel syndrome (IBS). The search spanned from the establishment of the database until September 1, 2023. Revman 5.4 and Stata 15.0 software were used for network meta-analysis (NMA), and the included interventions were ranked by the area under the cumulative ranking curve. RESULTS: A total of 26 articles involving 8 interventions were included. In terms of improving HAMA score, MOX was superior to EA, combined therapies, CH, WM and placebo; In terms of improving HAMD score, MOX was superior to ACU, EA, combined therapies, WM and placebo; In terms of improving the SAS score, The combined therapies were superior to EA, CH and WM; In terms of improving SDS scores, The combined therapies were superior to EA, CH and WM; In terms of improving IBS-SSS score, The combined therapies were superior to WM; In terms of reducing recurrence rates, CH was superior to combined therapies; In terms of improving total effective rates, MOX was superior to EA, CH, WM and placebo; MOX, combined therapies, ACU and EA ranked higher in SUCRA of different outcome indicators. CONCLUSION: MOX, combined therapies, ACU and EA have certain curative effect on anxiety and depression in patients with IBS-D, and their safety is high. ACU and MOX combined with other therapies also have significant advantages in the treatment effect.

Into the era of mycobiome-driven cancer research.

The cancer mycobiome has recently become a research hotspot. While the intratumor mycobiota is implicated in cancer initiation and progression, the gut mycobiota functions as biomarkers for cancer diagnosis and treatment. In this forum article we highlight the involvement of the mycobiome in correlation-, causation-, and prediction-oriented cancer research and discuss the potential of this burgeoning field.

Reclamation history and land use types across multiple spatial scales shape anuran communities in the coastal land reclamation region.

Land reclamation is a widely adopted method for managing land shortage and promoting coastal economic development globally. However, its impacts on biodiversity vary based on distinct reclamation histories and land use management strategies in different regions. This study aims to examine the effects of reclamation history and land use types at different spatial scales on anuran communities in coastal reclaimed land, which are an important taxon in the coastal ecosystem. We used visual and acoustic encounter methods to survey anurans in 2016 and 2017 across 20 1-km radius coastal land reclamation landscapes with different reclamation histories (10, 20, and 60 y after reclamation) in Nanhui Dongtan of Shanghai, an important coastal land reclamation region along the Yangtze River Estuary. Landscape variables (farmlands, woodlands, and impermeable surface covers, and the landscape Shannon diversity index) at four different spatial scales (250 m, 500 m, 750 m and 1000 m) and water salinity in each landscape were measured. Our findings reveal differences in anuran communities between study sites with 10, 20, and 60 years of reclamation history. Abundances of the ornamented pygmy frog (Microhyla fissipes) and Beijing gold-striped pond frog (Pelophylax plancyi) in landscapes with a 10-year reclamation history were significantly lower compared to those with histories of 20 and 60 years. Zhoushan toad (Bufo gargarizans) abundance was significantly negatively related to farmland cover at the 1000 m scale and impermeable surface cover at the 250 m scale; Hong Kong rice-paddy frog (Fejervarya multistriata) abundance was significantly positively related to farmland cover at the 1000 m scale; ornamented pygmy frog abundance was positively related to farmland cover at the 1000 m scale; and Beijing gold-striped pond frog abundance was significantly positively and negatively related to the landscape Shannon diversity index at the 1000 m scale and to water salinity, respectively. Amphibians quickly migrated and colonized coastal reclaimed land from older natural lands. However, two anuran species with specific habitat requirements tended to avoid areas with shorter reclamation histories. The single-species models revealed different responses to various land uses at the various scales, which indicated that land use management was important to amphibian conservation in coastal reclamation regions.

Global fungal-host interactome mapping identifies host targets of candidalysin.

Candidalysin, a cytolytic peptide toxin secreted by the human fungal pathogen Candida albicans, is critical for fungal pathogenesis. Yet, its intracellular targets have not been extensively mapped. Here, we performed a high-throughput enhanced yeast two-hybrid (HT-eY2H) screen to map the interactome of all eight Ece1 peptides with their direct human protein targets and identified a list of potential interacting proteins, some of which were shared between the peptides. CCNH, a regulatory subunit of the CDK-activating kinase (CAK) complex involved in DNA damage repair, was identified as one of the host targets of candidalysin. Mechanistic studies revealed that candidalysin triggers a significantly increased double-strand DNA breaks (DSBs), as evidenced by the formation of γ-H2AX foci and colocalization of CCNH and γ-H2AX. Importantly, candidalysin binds directly to CCNH to activate CAK to inhibit DNA damage repair pathway. Loss of CCNH alleviates DSBs formation under candidalysin treatment. Depletion of candidalysin-encoding gene fails to induce DSBs and stimulates CCNH upregulation in a murine model of oropharyngeal candidiasis. Collectively, our study reveals that a secreted fungal toxin acts to hijack the canonical DNA damage repair pathway by targeting CCNH and to promote fungal infection.

The intersection of virus infection and liver disease: A comprehensive review of pathogenesis, diagnosis, and treatment.

Liver disease represents a significant global burden, placing individuals at a heightened risk of developing cirrhosis and liver cancer. Viral infections act as a primary cause of liver diseases on a worldwide scale. Infections involving hepatitis viruses, notably hepatitis B, C, and E viruses, stand out as the most prevalent contributors to acute and chronic intrahepatic adverse outcome, although the hepatitis C virus (HCV) can be effectively cured with antiviral drugs, but no preventative vaccination developed. Hepatitis B virus (HBV) and HCV can lead to both acute and chronic liver diseases, including liver cirrhosis and hepatocellular carcinoma (HCC), which are principal causes of worldwide morbidity and mortality. Other viruses, such as Epstein-Barr virus (EBV) and cytomegalovirus (CMV), are capable of causing liver damage. Therefore, it is essential to recognize that virus infections and liver diseases are intricate and interconnected processes. A profound understanding of the underlying relationship between virus infections and liver diseases proves pivotal in the effective prevention, diagnosis, and treatment of these conditions. In this review, we delve into the mechanisms by which virus infections induce liver diseases, as well as explore the pathogenesis, diagnosis, and treatment of liver diseases. This article is categorized under: Infectious Diseases > Biomedical Engineering.

Internet use, physical activity and depressive symptoms in older adults: A cross-lagged panel analysis.

BACKGROUND: Existing cross-sectional studies suggest a strong positive association between Internet use, physical activity, and mental health in older adults; however, longitudinal studies reporting the relationship between Internet use, physical activity, and levels of depressive symptoms in older adults are lacking. This study aimed to examine the bidirectional relationship between Internet use and depressive symptoms in older adults and its underlying mechanisms. METHODS: We used two waves of follow-up data (2016 and 2018) from the China Family Panel Studies, including 5837 participants aged 60 years or above. The bidirectional relationship between Internet usage time and depressive symptoms was examined using a cross-lagged model. The mediating role of physical exercise was examined using a half-longitudinal mediation model. RESULTS: The results revealed a bidirectional relationship between Internet use time, frequency of physical activity, and depressive symptoms. Longer Internet use predicted lower levels of depressive symptoms, and the frequency of physical activity mediated the longitudinal relationship between Internet use and depressive symptoms in older adults. LIMITATIONS: First, our study used self-report-based variables. Second, our study did not obtain the specific timing of the application of various functions of the Internet and the intensity of physical activity among older adults. Finally, based on the availability of data, our study involved only two waves of data. This may not be sufficient for a full longitudinal mediation effect test. CONCLUSIONS: Internet use and depressive symptoms were interrelated over time among older adults. The frequency of physical activity was a mediator of Internet use and depressive symptoms. This underscores the importance of Internet-based technologies to enable healthy living and prevent depression and loneliness in older adults.