Risk factors for vaginal squamous intra-epithelial lesions in women with high-grade cervical lesions.

OBJECTIVE: To investigate the high-risk factors associated with concurrent cervical intra-epithelial neoplasia (CIN) and vaginal intra-epithelial neoplasia (VaIN) in patients with high-grade lesions. METHODS: This retrospective study at the Obstetrics and Gynecology Hospital of Fudan University included patients diagnosed with concurrent CIN2/3 and VaIN2/3 (concurrent group) over the period from January 1, 2019, to December 31, 2019. Patients with only CIN2/3 during the corresponding period were selected chronologically on a 1:2 basis (CIN group). Demographic data, human papillomavirus (HPV) infection rates, genotypes, and cytology results were compared between the groups. RESULTS: A total of 128 patients were included. The median age in the concurrent group was 50 years (range 20-79), which was significantly higher than the median age of 38 (range 23-72) in the CIN group (p<0.001). The cytological sensitivity for identifying high-grade lesions was markedly higher in the concurrent group at 83.1% (103 out of 124) compared with 68.4% (175 out of 256) in the CIN-only group (p=0.002). The prevalence of HPV 16 was 62.8% in the concurrent group, significantly higher than 51.6% in the CIN group (p=0.04). CONCLUSIONS: The risk of concurrent VaIN2/3 increases with age among women with CIN2/3. Cytology screening is effective for detecting concurrent VaIN2/3, with a sensitivity of 83.1%.

Effectiveness of magnetic resonance imaging and spiral computed tomography in the staging and treatment prognosis of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is a prevalent cancer type in clinical settings; its early signs can be difficult to detect, which often results in late-stage diagnoses in many patients. The early detection and diagnosis of CRC are crucial for improving treatment success and patient survival rates. Recently, imaging techniques have been hypothesized to be essential in managing CRC, with magnetic resonance imaging (MRI) and spiral computed tomography (SCT) playing a significant role in enhancing diagnostic and treatment approaches. AIM: To explore the effectiveness of MRI and SCT in the preoperative staging of CRC and the prognosis of laparoscopic treatment. METHODS: Ninety-five individuals admitted to Zhongshan Hospital Xiamen University underwent MRI and SCT and were diagnosed with CRC. The precision of MRI and SCT for the presurgical classification of CRC was assessed, and pathological staging was used as a reference. Receiver operating characteristic curves were used to evaluate the diagnostic efficacy of blood volume, blood flow, time to peak, permeability surface, blood reflux constant, volume transfer constant, and extracellular extravascular space volume fraction on the prognosis of patients with CRC. RESULTS: Pathological biopsies confirmed the following CRC stages: 23, 23, 32, and 17 at T1, T2, T3, and T4, respectively. There were 39 cases at the N0 stage, 22 at N1, 34 at N2, 44 at M0 stage, and 51 at M1. Using pathological findings as the benchmark, the combined use of MRI and SCT for preoperative TNM staging in patients with CRC demonstrated superior sensitivity, specificity, and accuracy compared with either modality alone, with a statistically significant difference in accuracy (P < 0.05). Receiver operating characteristic curve analysis revealed the predictive values for laparoscopic treatment prognosis, as indicated by the areas under the curve for blood volume, blood flow, time to peak, and permeability surface, blood reflux constant, volume transfer constant, and extracellular extravascular space volume fraction were 0.750, 0.683, 0.772, 0.761, 0.709, 0.719, and 0.910, respectively. The corresponding sensitivity and specificity values were also obtained (P < 0.05). CONCLUSION: MRI with SCT is effective in the clinical diagnosis of patients with CRC and is worthy of clinical promotion.

The immune landscape in apical periodontitis: From mechanism to therapy.

Apical periodontitis (AP) is featured by a persistent inflammatory response and alveolar bone resorption initiated by microorganisms, posing risks to both dental and systemic health. Nonsurgical endodontic treatment is the recommended treatment plan for AP with a high success rate, but in some cases, periapical lesions may persist despite standard endodontic treatment. Better comprehension of the AP inflammatory microenvironment can help develop adjunct therapies to improve the outcome of endodontic treatment. This review presents an overview of the immune landscape in AP, elucidating how microbial invasion triggers host immune activation and shapes the inflammatory microenvironment, ultimately impacting bone homeostasis. The destructive effect of excessive immune activation on periapical tissues is emphasized. This review aimed to systematically discuss the immunological basis of AP, the inflammatory bone resorption and the immune cell network in AP, thereby providing insights into potential immunotherapeutic strategies such as targeted therapy, antioxidant therapy, adoptive cell therapy and cytokine therapy to mitigate AP-associated tissue destruction.

Identification of a novel xanthine oxidoreductase inhibitor for hyperuricemia treatment with high efficacy and safety profile.

Hyperuricemia is with growing incidence and of high risk to develop into gout and other metabolic diseases. The key enzyme catalyzing uric acid synthesis, xanthine oxidoreductase (XOR) is a vital target for anti-hyperuricemic drugs, while XOR inhibitors characterized as both potent and safe are currently in urgent need. In this study, a novel small molecule compound, CC15009, was identified as a specific XOR inhibitor. CC15009 exerted strongest in vitro XOR inhibitory activity among current XOR inhibitors. It also showed favorable dose-dependent uric acid-lowering effects in two different XOR substrate-induced hyperuricemic mouse models, which was significantly superior than the current first-line drug, allopurinol. Mechanically, the direct binding of CC15009 against XOR was confirmed by molecular docking and SPR analysis. The inhibition mode was competitive and reversible. Besides, the potential antioxidant activity of CC15009 was indicated by its strong inhibitory activity against the oxidized isoform of XOR, which reduced ROS generation as the byproduct. Regarding the safety concerns of current XOR inhibitors, especially in cardiovascular risks, the safety of CC15009 was comprehensively evaluated. No significant abnormality was observed in the acute, subacute toxicity tests and mini-AMES test. Notably, there was no obvious inhibition of CC15009 against cardiac ion channels, including hERG, Nav1.5, Cav1.2 at the concentration of 30 µM, indicating its lower cardiovascular risk. Taken together, our results supported CC15009 as a candidate of high efficacy and safety profile to treat hyperuricemia through direct XOR inhibition.

Microbial nitrogen nutrition links to dissolved organic matter properties in East African lakes.

East African lakes, especially soda lakes, are home habitats for massive numbers of wildlife such as flamingos, mammals, and fishes. These lakes are known for their high primary production due to local high temperatures, light intensities, and alkalinity (inorganic carbon). However, these lakes, normally within remote areas, receive low nutrient inputs. Ammonium (NH4+) recycling and/or nitrogen fixation can become the major N supply mechanisms for phytoplankton. However, the driving forces of microbial N nutrition in lakes with minimal anthropogenic disturbance remain poorly understood. Using stable isotope tracer techniques, NH4+ recycling rates were measured in 18 lakes and reservoirs in East Africa (Tanzania and Kenya) during the dry season in early 2020. Three functional genes (nifH, gdh, and UreC) relating to microbial N nutrition were also measured. The NH4+ regeneration supported up to 71 % NH4+ uptake. Positive community biological NH4+ demands (CBAD) for all lakes and reservoirs indicate an obvious N demand from microbial community. Our study provides clear evidence that microbial NH4+ uptake rates are closely linked to the dissolved organic matter (DOM) properties (e.g., the absorption coefficient at 254 nm, percents of total fluorescence intensity contributed by microbial humic-like and protein-like components) and that water residence time drives microbial NH4+ recycling by regulating the duration of in-lake DOM processing and influencing algal growth. Phytoplankton, especially those of Cyanophyceae, showed maximum biomass and higher NH4+ recycling rates at a certain range of water residence time (e.g., 5-8 years). However, CBAD showed a decreasing trend with longer water residence time, which may be influenced by changes in the algal community composition (e.g., % Cyanophyceae vs. % Bacillariophyceae). These results indicate that the water residence time and DOM dynamics have the potential to facilitate the understanding of microbial nitrogen supply mechanisms in East African lakes.

A kinase fusion protein from Aegilops longissima confers resistance to wheat powdery mildew.

Many disease resistance genes have been introgressed into wheat from its wild relatives. However, reduced recombination within the introgressed segments hinders the cloning of the introgressed genes. Here, we have cloned the powdery mildew resistance gene Pm13, which is introgressed into wheat from Aegilops longissima, using a method that combines physical mapping with radiation-induced chromosomal aberrations and transcriptome sequencing analysis of ethyl methanesulfonate (EMS)-induced loss-of-function mutants. Pm13 encodes a kinase fusion protein, designated MLKL-K, with an N-terminal domain of mixed lineage kinase domain-like protein (MLKL_NTD domain) and a C-terminal serine/threonine kinase domain bridged by a brace. The resistance function of Pm13 is validated through transient and stable transgenic complementation assays. Transient over-expression analyses in Nicotiana benthamiana leaves and wheat protoplasts reveal that the fragment Brace-Kinase122-476 of MLKL-K is capable of inducing cell death, which is dependent on a functional kinase domain and the three α-helices in the brace region close to the N-terminus of the kinase domain.

OsWNK9 regulates cadmium concentration in brown rice by restraining cadmium transport from straw to brown rice.

Selecting and breeding rice cultivars that enable strong cadmium (Cd) accumulation in rice straw but low accumulation in brown rice is a promising way to achieve Cd phytoremediation as well as to ensure the food safety of rice. Herein, we isolated a gene OsWNK9 from the quantitative trait locus associated with reducing Cd translocation from rice straw to brown rice and decreasing the Cd concentration in brown rice (BRCdC). Continuous strong expression of OsWNK9 was observed in nodes and internode and was induced after Cd supply. OsWNK9 was localized in the rice cell nucleus and participated in the regulation of Cd transport in yeast. Two independent oswnk9 rice mutants were generated via CRISPR/Cas9 gene-editing and showed significantly higher BRCdC than that of the wild type (WT). The BRCdC of knockout oswnk9 mutants was 0.227 mg kg-1and 0.238 mg kg-1, increased by 14 % and 19 % compared with that of the WT due to the lower Cd allocation in the basal stem, internode, and node III, which was unrelated to Cd uptake. Interestingly, OsWNK9 could promote iron (Fe) accumulation in rice under Cd-contaminated conditions, suggesting that OsWNK9 is an ideal gene for Cd phytoremediation and Fe biofortification in rice to support safe food production.

Bruton's tyrosine kinase inhibition ameliorated neuroinflammation during chronic white matter ischemia.

Chronic cerebral hypoperfusion (CCH), a disease afflicting numerous individuals worldwide, is a primary cause of cognitive deficits, the pathogenesis of which remains poorly understood. Bruton's tyrosine kinase inhibition (BTKi) is considered a promising strategy to regulate inflammatory responses within the brain, a crucial process that is assumed to drive ischemic demyelination progression. However, the potential role of BTKi in CCH has not been investigated so far. In the present study, we elucidated potential therapeutic roles of BTK in both in vitro hypoxia and in vivo ischemic demyelination model. We found that cerebral hypoperfusion induced white matter injury, cognitive impairments, microglial BTK activation, along with a series of microglia responses associated with inflammation, oxidative stress, mitochondrial dysfunction, and ferroptosis. Tolebrutinib treatment suppressed both the activation of microglia and microglial BTK expression. Meanwhile, microglia-related inflammation and ferroptosis processes were attenuated evidently, contributing to lower levels of disease severity. Taken together, BTKi ameliorated white matter injury and cognitive impairments induced by CCH, possibly via skewing microglia polarization towards anti-inflammatory and homeostatic phenotypes, as well as decreasing microglial oxidative stress damage and ferroptosis, which exhibits promising therapeutic potential in chronic cerebral hypoperfusion-induced demyelination.

Primary and Orthotopic Murine Models of Nasopharyngeal Carcinoma Reveal Molecular Mechanisms Underlying its Malignant Progression.

Nasopharyngeal carcinoma (NPC), a squamous cell carcinoma originating in the nasopharynx, is a leading malignancy in south China and other south and east Asia areas. It is frequently associated with Epstein-Barr virus (EBV) infection, while there are also some NPC patients without EBV infection. Here, it is shown that the EBV+ (EBV positive) and EBV- (EBV negative) NPCs contain both shared and distinct genetic abnormalities, among the latter are increased mutations in TP53. To investigate the functional roles of NPC-associated genetic alterations, primary, orthotopic, and genetically defined NPC models were developed in mice, a key tool missed in the field. These models, initiated with gene-edited organoids of normal nasopharyngeal epithelium, faithfully recapitulated the pathological features of human disease. With these models, it is found that Trp53 and Cdkn2a deficiency are crucial for NPC initiation and progression. And latent membrane protein1 (LMP1), an EBV-coding oncoprotein, significantly promoted the distal metastasis. Further, loss of TGFBR2, which is frequently disrupted both in EBV- and EBV+ NPCs, dramatically accelerated the progression and lung metastasis of NPC probably by altering tumor microenvironment. Taken together, this work establishes a platform to dissect the genetic mechanisms underlying NPC pathogenesis and might be of value for future translational studies.

Panniculus Retractor Use for Visualization of Fetal Anatomy: A Randomized Controlled Trial.

OBJECTIVE: To evaluate whether use of a panniculus retractor device for pregnant patients with body mass index (BMI) 40 or higher and a panniculus improves the completion rate of the fetal anatomic examination. METHODS: This was a randomized trial in which eligible patients with BMI 40 or higher and a panniculus were randomized to undergo their detailed fetal anatomic examination with a panniculus retractor device in place compared with usual care. The primary outcome was the completion rate of 16 prespecified views from the anatomic examination. Secondary outcomes included completion rate of all 64 views from our institution's detailed anatomic examination, duration of examination, major fetal anomaly detection rate, depth from the skin to amniotic cavity before and after retractor placement, patient and ultrasonographer satisfaction, and prespecified adverse events. We assumed a baseline completion rate of 23% for the primary outcome and targeted a twofold improvement with 80% power and two-sided α of 0.05, which resulted in a sample size of 132 participants. The goal enrollment was increased to 150 participants to account for potential dropout. Statistical tests included the Student's t test, χ2, and relative risks (RRs) as appropriate. RESULTS: From March to July of 2023, 150 participants completed the study: 74 in the retractor group and 76 in the usual care group. Baseline characteristics were similar between groups except for panniculus grade. The completion rate of 16 prespecified views was 25.7% (19/74) in the retractor group and 31.6% (24/76) in the control group (RR 0.81, 95% CI, 0.49-1.35). There were no significant differences between groups for any of the secondary outcomes. Patient satisfaction and ultrasonographer satisfaction were similar between groups. CONCLUSION: Use of a panniculus retractor device during the fetal anatomic examination for patients with BMI 40 or higher and a panniculus was well tolerated by patients and ultrasonographers but did not improve the completion rate of 16 prespecified fetal anatomic views. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, NCT05764408.

Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study.

Recurrence risks of cancer patient can change during treatment as a result of treatment-related tumor evolution. However, biomarkers that can monitor these changes are lacking. Here, we investigated whether tracking circulating tumor DNA (ctDNA) dynamics through liquid biopsy can inform real-time recurrence risk. Nasopharyngeal carcinoma (NPC) provides an ideal model where cell-free Epstein-Barr virus (EBV) DNA (cfEBV DNA), a ctDNA, can be sensitively detected. We conducted the EP-SEASON study (NCT03855020) and prospectively recruited 1,000 NPC patients undergoing per-protocol cfEBV DNA assessments at 11 time points and receiving sequential chemo-radiotherapy. Longitudinal cfEBV DNA displayed distinct patterns during neoadjuvant chemotherapy and radiotherapy. Despite the prognostic significance of cfEBV DNA at each time point, real-time recurrence risks changed in sync with cfEBV DNA dynamics. Furthermore, we identified phenotypes of whole-course ctDNA changing dynamics associated with different survival outcomes. In conclusion, tracking longitudinal on-treatment ctDNA can forecast real-time recurrence risk, facilitating risk-adapted, individualized patient management.

Non-equilibrium transport in polymer mixed ionic-electronic conductors at ultrahigh charge densities.

Conducting polymers are mixed ionic-electronic conductors that are emerging candidates for neuromorphic computing, bioelectronics and thermoelectrics. However, fundamental aspects of their many-body correlated electron-ion transport physics remain poorly understood. Here we show that in p-type organic electrochemical transistors it is possible to remove all of the electrons from the valence band and even access deeper bands without degradation. By adding a second, field-effect gate electrode, additional electrons or holes can be injected at set doping states. Under conditions where the counterions are unable to equilibrate in response to field-induced changes in the electronic carrier density, we observe surprising, non-equilibrium transport signatures that provide unique insights into the interaction-driven formation of a frozen, soft Coulomb gap in the density of states. Our work identifies new strategies for substantially enhancing the transport properties of conducting polymers by exploiting non-equilibrium states in the coupled system of electronic charges and counterions.

Deletion of vitamin D receptor exacerbated temporomandibular joint pathological changes under abnormal mechanical stimulation.

AIMS: Temporomandibular disorder can cause degenerative pathological changes by aseptic inflammation in the temporomandibular joint (TMJ). Vitamin D (VD) is known for maintaining calcium homeostasis, and recent studies indicated that VD and the vitamin D receptor (VDR) are important in inflammatory responses. In this study, we explored the anti-inflammatory effect of VD-VDR signaling axis in TMJ pathological degeneration. MAIN METHODS: Mice ablated for Vdr (Vdr-/-res) were fed with a rescue diet to avoid hypocalcemia. With abnormal mechanical stimulation, unilateral anterior crossbite (UAC) induced temporomandibular disorders in mice. Histological staining, immunohistochemistry staining, and micro-CT analysis were performed to evaluate TMJ pathological changes. To identify the mechanisms in the aseptic inflammatory process, in vitro experiments were conducted on wild-type (WT) and Vdr-/- chondrocytes with compressive mechanical stress loading, and the related inflammatory markers were examined. KEY FINDINGS: Vdr-/-res mice did not develop rickets with a high calcium rescue diet. The TMJ cartilage thickness in Vdr-/-res mice was significantly decreased with mechanical stress stimulation compared to WT mice. UAC-induced bone resorption was obvious, and the number of osteoclasts significantly increased in Vdr-/-res mice. The proliferation was inhibited and the gene expression of Il1b, Mmp3, and Mmp13 was significantly increased in Vdr-/- chondrocytes. However, WT chondrocytes showed significantly increased Tnfa gene expression as a response to mechanical stress but not in Vdr-/- chondrocytes. SIGNIFICANCE: VD-VDR is crucial in TMJ pathological changes under abnormal mechanical stimulation. Deletion of Vdr exacerbated inflammatory response excluding TNFα, inhibited chondrocyte proliferation, and promoted bone resorption in TMJ.

Demographic and clinical characteristics and risk factors of stereoacuity in convergence insufficiency-type intermittent exotropia.

Purpose: To investigate characteristics and risk factors of poor stereoacuity of Convergence insufficiency-type Intermittent Exotropia (CI-type X(T)). Design: Observational, cross-sectional study. Methods: The medical records of 615 CI-type X(T) and 222 basic-type intermittent exotropia (X(T)) were enrolled from January 2018 to January 2022. The characteristics were compared between the two types, and the associations between clinical factors and poor stereoacuity were examined using logistic regression. Results: Compared with basic-type X(T), earlier surgery age, shorter misalignment duration, and the smaller distance exodeviation were observed in CI-type X(T). The CI-type X(T) demonstrated better sensory status and lower incidence of ocular muscle dysfunction than did the basic-type X(T). The surgery age between 6 and 12 years (odds ratio [OR], 0.595; compared with ≤6 years) was inversely associated with poor near stereoacuity, whereas duration more than 4 years (OR, 2.474), amblyopia (OR, 4.057), large distance exodeviation (>60PD: OR, 2.462) and anisometropia (>2.00D: OR, 3.874) were positively associated with poor near stereoacuity. The onset age older than 6 years (6-9 years: OR, 0.397; >9 years: OR, 0.317) was associated with better distance stereoacuity, whereas large distance exodeviation (>60PD: OR, 23.513), and dominant eye best corrected visual acuity (BCVA) worsen than 0.20 (OR, 2.987) were positively associated with poor distance stereoacuity. Conclusion: CI-type X(T) declined surgery early, with small distance exodeviation, better sensory status, and low incidence of ocular muscle dysfunction. A strong dose-dependent link between early onset age, long misalignment duration, worse dominant eye BCVA, distance exodeviation, amblyopia, anisometropia, and poor stereoacuity was confirmed.

Chinese herbal compound preparation Qing-Xin-Jie-Yu granules for intermediate coronary lesions in patients with stable coronary artery disease: Study protocol for a multicenter, randomized, double-blind, placebo-controlled trial.

INTRODUCTION: Despite the available secondary preventive treatments, the management of stable coronary artery disease (SCAD) remains challenging. Intermediate coronary lesion (ICL), defined as luminal stenosis between 50% and 70%, is a key stage of SCAD. However, existing therapeutic strategies are limitated in delaying plaque progression and associated with various adverse effects and economic burdens. Qing-Xin-Jie-Yu Granules (QXJYG) with proven anti-platelet, anti-inflammatory, and lipid-lowering effects may compensate for the drawbacks of current treatments and can be tested as a complementary therapy. Therefore, this study aims to investigate the efficacy and safety of QXJYG in treating ICL, with a particular focus on its impact on myocardial ischemia and plaque progression. MATERIALS AND METHODS: This is a multicenter, randomized, double-blind, placebo-controlled trial. A total of 120 participants with ICL will be randomly assigned to two groups in a 1:1 ratio. In addition to basic medications, the intervention group will receive QXJYG, while the control group will receive a placebo for over 6 months, followed by a 12-month follow-up. The primary efficacy outcome is computed tomography-derived fractional flow reserve. The secondary outcomes include the degree of coronary stenosis, coronary artery calcification score, Gensini score, Seattle Angina Questionnaire score, high-sensitivity C-reactive protein, matrix metalloproteinase-9, blood lipids, and carotid artery ultrasound parameters. Major adverse cardiovascular events are recorded as endpoints. The safety outcomes include composite events of bleeding, laboratory test results, and adverse events. Clinical visits are scheduled at baseline, every 2 months during the treatment, and after a 12-month follow-up. DISCUSSION: This trial is anticipated to yield reliable results to verify the efficacy and safety of QXJYG in the treatment of ICL, which will provide novel insights to help address the prevailing therapeutic dilemma of ICL, thereby facilitating for the management of SCAD. TRIAL REGISTRATION: Chinese Clinical Trial Registry, ChiCTR2200059262. Registered on April 27, 2022.

Gradient Hierarchically Porous Ionic-Junction Fibers of Wet-Spun Carboxymethyl Cellulose Coagulated with Copper Sulfate.

Polyelectrolyte-based ionic-junction fibers newly serve as signal transmission and translation media between electronic devices and biological systems, facilitating ion transport within organic matrices. In this work, we fabricated gel filaments of carboxymethyl cellulose (CMC) chelated with Cu(II) ions through wet-spinning, using a saturated coagulant of CuSO4. Interestingly, the as-spun fibers exhibited dramatic 3D porous frameworks that varied with the temperature and precursor concentration. At 20 °C, the Cu(II) chelation networks favored the formation of well-organized cellular chambers or corrugated channels, displaying dense stacking patterns. However, critical transitions from cellular chambers to corrugated channels occurred at precursor dope concentrations of approximately 2 and 7 wt %, with the porous structure diminishing beyond 8 wt %. We have proposed schematic diagrams to mimic the 3D pore structure, dense porous stacking, and formation mechanism, according to electronic micrographs. Our investigations revealed that the distinct ion-junction channels or chambers are under the control of axial drawing extension as well as the outside-inside penetration of Cu(II) ions into the dope and inside-outside diffusion of water into coagulants. Therefore, controlling the metal chelation-water diffusion process at specific temperatures and concentrations will offer valuable insights for tailoring ionic-junction soft filaments with gradient hierarchically porous structures and shape memory properties.

Optimization of Eisenia fetida stocking density for biotransformation during green waste vermicomposting.

Appropriate stocking density plays an important role in ensuring the stability and improving the overall efficiency of the vermicomposting system. Although some studies have shown that earthworms can degrade lignocellulosic materials, relatively few studies have been conducted on the effect of earthworm stocking density on the degradation of a single green waste (GW) with high lignocellulosic content. Therefore, this study investigated the degradation effect of earthworms on GW at different stocking densities, and assessed the stability and maturity of the whole vermicomposting by comprehensively analysing the changes in physicochemical and biological properties of earthworms during vermicomposting, and by combining the growth of earthworms with a multi-dimensional assessment of the stability and maturity of the whole vermicomposting. In this study, six stocking densities (CK-T5) were set up, namely, no earthworms, 10, 20, 30, 40, and 50 worms/kg. The results showed that compared with the CK (without earthworms), when there were 30 earthworms per kg of GW (i.e. T3), the total nitrogen, total phosphorus, total potassium, organic matter decomposition, bacterial and fungal numbers, and germination index of earthworm compost products increased by 14 %, 29 %, 32 %, 35 %, 42 %, 94 %, and 125 %, respectively. T3 also enhanced the activities of cellulase and alkaline phosphatase. The results were further supported by principal component analysis. Finally, we conclude that when the stocking density of earthworms is appropriate (T3), it not only favours the growth of earthworms, but also positively affects the physicochemical properties of the vermicomposting process, which in turn significantly improves the biodegradation efficiency of GW.

Gut microbiota affects the activation of STING pathway and thus participates in the progression of colorectal cancer.

BACKGROUND: More and more studies showed that gut microbiota was closely related to the development of colorectal cancer (CRC). However, the specific pathway of gut microbiota regulating CRC development is still unknown. METHODS: We collected fecal samples from 14 CRC patients and 20 normal volunteers for 16 S sequencing analysis. At the same time, 14 CRC patients' tumors and their adjacent tissues were collected for the detection of STING pathway related protein level. Mice were injected with azoxymethane (AOM) to establish an animal model of CRC, and antibiotics were given at the same time to evaluate the influence of gut microbiota on STING pathway and whether it was involved in regulating the tumor development of CRC mice. RESULTS: The sequencing results showed that compared with the normal group, the gut microbiota gut microbiota of CRC patients changed significantly at different species classification levels. At the level of genus, Akkermansia, Ligilactobacillus and Subdoligranulum increased the most in CRC patients, while Bacteroides and Dialister decreased sharply. The expression of STING-related protein was significantly down-regulated in CRC tumor tissues. Antibiotic treatment of CRC mice can promote the development of tumor and inhibit the activation of STING pathway. CONCLUSION: Gut microbiota participates in CRC progress by mediating STING pathway activation.

Transcriptome-Based Analysis of the Mechanism of Action of Metabolic Disorders Induced by Waterborne Copper Stress in Coilia nasus.

To reveal the effects of waterborne copper stress on gene expression changes, molecular pathways, and physiological functions in Coilia nasus, juvenile fish were equally divided into two experimental groups, and the copper levels were 1.61 ± 0.03 mg/L (copper-exposed group) and 0 mg/L (control group), respectively. After 4 h, gill tissue samples were collected for transcript sequencing analysis, and two libraries were constructed from the copper treatment group (Cu) and the control group (C) and sequenced using Illumina sequencing technology. The results showed that approximately 40.2-46.0 M clean reads were obtained from each library, and the percentage of uniquely mapped transcripts ranged from 80.57 to 84.93%. A total of 3915 differentially expressed genes (DEGs) were identified under waterborne copper stress, among which 1300 genes were up-regulated, and 2615 genes were down-regulated. Twelve DEGs were randomly selected for quantitative RT-PCR (qRT-PCR) analysis, and the results confirmed that the transcriptome analysis was reliable. Furthermore, the DEGs were subjected to Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and the results showed that most of the DEGs were involved in metabolic pathways, including steroid biosynthesis, glutathione metabolism, and peroxisome proliferator-activated receptor (PPAR) signaling pathways. Furthermore, due to the waterborne copper levels, gsk-3ß was significantly up-regulated, while other metabolism-related genes (tor, pi3k, lpl, aqp7, fabp3) were significantly down-regulated. In addition, the copper-exposed group significantly reduced the expression of some immunity genes (ifn-γ, stat1, cxcl10, and tgf-ß), and enhanced the expression of il-1ß and tnf-α. In summary, these results indicated that copper causes metabolic disorders and insufficient energy supply in the body, and induces oxidative stress, which results in reduced immune functions.

Exendin-4 Caused Growth Arrest by Regulating Sugar Metabolism in Hyphantria cunea (Lepidoptera: Erebidae) Larvae.

Insects' growth and development are highly dependent on energy supply, with sugar metabolism playing a pivotal role in maintaining homeostasis and regulating physiological processes. The present study investigated the effects of exendin-4, a glucagon-like peptide-1 receptor (GLP-1R) agonist, on the growth, development, glycolysis, and energy metabolism of fourth-instar larvae of the fall webworm, Hyphantria cunea. We determined the impact of exendin-4 on larval growth and nutritional indices, analyzed the responses of glycolytic and metabolic pathways, and revealed the underlying regulatory mechanisms. Exendin-4 treatment significantly decreased growth and nutritional indices, influenced the activity of digestive enzymes, and induced changes in metabolite profiles, particularly affecting energy substance metabolism. We observed an increase in the glycogen content and a decrease in glucose and trehalose levels in the hemolymph, suggesting a regulatory effect on blood sugar homeostasis. Furthermore, exendin-4 promoted glycolysis by enhancing the activities and expressions of key glycolytic enzymes, leading to an increase in pyruvate production. This was accompanied by a reduction in ATP levels and the activation of AMP-activated protein kinase (AMPK), which may underlie the growth arrest in larvae. Our findings provide novel insights into the effects of exendin-4 on insect responses from an energy metabolism perspective and may contribute to the development of GLP-1R agonists for pest management.