Search

Effects of four types of cereal dietary fibers (DF) on blood glucose, inflammatory factors and gut microbiota in db/db mice were investigated. The db/db mice were fed with diets containing four types of dietary fibers of wheat (WDF), brown rice (BDF), oat (ODF) and buckwheat (BWDF) respectively. The fasting blood glucose (FBG) level was measured every two weeks, and oral glucose tolerance tests (OGTT) were conducted at the 8th and 14th weeks. At 14 weeks, feces were collected to analyze the changes of microbiota, and serum was collected to determine the level of blood lipid and inflammatory factors. Four types of cereal DF could reduce the FBG and the area under the blood glucose curve (AUC) at 8 weeks in db/db mice, improve dyslipidemia and reduce the concentration of blood pro-inflammatory factors (P < 0.05). All four types of cereal DF could increase the diversity of gut microbiota and change the abundance of different microbiota. Among them, WDF mainly increased the abundance of Faecalibaculum and Romboutsia, BDF increased the abundance of Actinobacteriota and the ratio of Firmicutes to Bacteroidota (F/B), ODF mainly promoted the proliferation of Alistipes, and BWDF increased the abundance of norank_f__Muribaculaceae and decreased the level of Bacteroides. Correlation analysis showed that F/B and Actinobacteriota were significantly negatively correlated with FBG, AUC, pro-inflammatory factor (IL-8) and low-density lipoprotein cholesterol (LDL-C) levels, and positively correlated with anti-inflammatory factor (IL-10) and high-density lipoprotein cholesterol (HDL-C) levels, while Bacteroides was the opposite. Alistipes, Faecalibaculum, and Romboutsia were negatively correlated with pro-inflammatory factors IL-1β, IL-8 and TNF-α respectively. Four types of cereal DF can improve the glycolipid metabolism disorder and inflammatory response in type 2 diabetic db/db mice by increasing the diversity of gut microbiota and exerting different regulatory effects on microbiota.

In the process of murder investigation, it is of great significance to find the discarded and buried human remains accurately. The main methods of searching for human remains include human visual search, aerial detection, geophysical technology, remote imaging technology and canine olfactory search technique. Canine olfactory search for human remains is a recognized time-effective and non-invasive search method, making dogs the most valuable search tool in forensic investigation. By systematically reviewing and summarizing relevant literature, and based on the theory of volatile organic compound produced by the decomposition of human remains, this paper explores the basic principle of the canine olfactory search technique for human remains. This paper also reviews the application of training canine search technique for human remains in forensic investigation by using human blood, tissue, cadaver putrefying fluid and odor substitutes as sniffing sources. The application prospect of canine olfactory search for human remains was prospected from the perspectives of detection of volatile organic compound during cadaver decay, development of odor substitutes and adsorption devices, and technology tactics used in canine training and use, to provide references for the relevant research of canine olfactory search for human remains in China.

Abstract Background Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria. Case presentation We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone. Conclusions Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren’t enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

AIM:To compare the corneal refractive power and visual quality after three kinds of corneal refractive surgery: laser subepithelial keratomileusis(LASEK), transepithelial photorefractive keratectomy(TransPRK)and femtosecond laser assisted in situ keratomileusis(FS-LASIK).METHODS: Retrospective study. A total of 232 patients(464 eyes)who underwent elective corneal refractive surgery in our hospital from January 2021 to December 2022 were selected as the study subjects. They were divided into the LASEK group of 70 cases(140 eyes), TransPRK group of 76 cases(152 eyes), and FS-LASIK group of 86 cases(172 eyes)according to the different surgical choices made by the patients. Uncorrected visual acuity(UCVA), visual quality, biomechanical stability, tear film break-up time(BUT), Schirmer Ⅰ test(SⅠt)and quality of life were compared among the three groups at 1 and 3 mo postoperatively.RESULTS: The UCVA of the three groups significantly improved at 1 and 3 mo postoperatively, the total high-order aberrations, spherical aberration, horizontal coma, and vertical coma of the entire cornea were significantly increased, while the biomechanical stability in all three groups were significantly reduced(all P0.05).CONCLUSION:In the treatment of ametropia, LASEK, TransPRK and FS-LASIK all have certain effects, and have similar results in improving UCVA and increasing visual quality. However, TransPRK and LASEK have more stable biomechanical properties than FS-LASIK, and have better efficacy in improving patients' quality of life.

Summary: Epstein-Barr virus (EBV), an oncogenic herpesvirus, is predominantly found in the latent infection form and is highly associated with many human malignancies, which mainly have poor prognoses and no effective treatments. Here, we obtained thirteen compounds from small-molecule libraries for specific inhibition of EBV-latently infected cell growth in vitro by high-throughput screening. Among them, cetrimonium bromide (CetB) was identified to selectively inhibit the growth of different EBV-infected B lymphoma cell lines. Importantly, CetB reduced EBNA1 protein stability, activated G1 arrest and early apoptosis of EBV-latently infected cells without viral lytic reactivation, which leads to dramatically inhibit colony formation and tumor growth of EBV-infected cells in vitro and in vivo, and significantly prolong the survival of tumor-bearing mice. Overall, these findings demonstrate that CetB acts as a highly selective inhibitor of the growth of EBV-infected cells and has the potential for further development of effective therapeutic strategies specific against EBV-associated cancers.

Transcriptional factor Forkhead box M1 (FOXM1) plays an important role in pancreatic ductal adenocarcinoma (PDAC) development and progression. The molecular mechanisms underlying its dysregulation remain unclear. We identified and functionally validated the microRNAs (miRNAs) that critically regulate FOXM1 expression in PDAC. The expression levels of miRNA-23a (miR-23a-3p and -5p) were altered in PDAC cell lines and their effects on FOXM1 signaling and cell proliferation and migration and tumorigenesis were examined in vitro and in vivo using mouse PDAC models. Compared with non-tumor pancreatic tissues, PDAC tissues and cell lines exhibited significantly reduced levels of miR-23a expression. Reduced miR-23a expression and concomitant increase in FOXM1 expression were also observed in acinar-to-ductal metaplasia and pancreatic intraepithelial neoplasia, the major premalignant lesions of PDAC. Transgenic expression of miR-23a reduced the expression of FOXM1 and suppressed cell proliferation and migration in PDAC cells, whereas the inhibitors of miR-23a did the opposite. Loss or reduced levels of miR-23a increased the levels of FOXM1 expression, while increased expression of FOXM1 down-regulated miR-23a expression, suggesting that miR-23a and FOXM1 were mutual negative regulators of their expression in PDAC cells. Therefore, the miR-23a/FOXM1 signaling axis is important in PDAC initiation and progression and could serve as an interventional or therapeutic target for patients with early or late stages of PDAC.

Abstract Gastric cancer (GC) is a major global health issue, being the fifth most prevalent cancer and the third highest contributor to cancer-related deaths. Although treatment strategies for GC have diversified, the prognosis for advanced GC remains poor. Hence, there is a critical need to explore new directions for GC treatment to enhance diagnosis, treatment, and patient prognosis. Extracellular vesicles (EVs) have emerged as key players in tumor development and progression. Different sources of EVs carry different molecules, resulting in distinct biological functions. For instance, tumor-derived EVs can promote tumor cell proliferation, alter the tumor microenvironment and immune response, while EVs derived from immune cells carry molecules that regulate immune function and possess tumor-killing capabilities. Numerous studies have demonstrated the crucial role of EVs in the development, immune escape, and immune microenvironment remodeling in GC. In this review, we discuss the role of GC-derived EVs in immune microenvironment remodeling and EVs derived from immune cells in GC development. Furthermore, we provide an overview of the potential uses of EVs in immunotherapy for GC.

Abstract Background Long non-coding RNAs (lncRNAs) play a crucial role in regulating gene expression vital for the growth and development of plants. Despite this, the role of lncRNAs in Chinese cabbage (Brassica rapa L. ssp. pekinensis) pollen development and male fertility remains poorly understood. Results In this study, we characterized a recessive genic male sterile mutant (366–2 S), where the delayed degradation of tapetum and the failure of tetrad separation primarily led to the inability to form single microspores, resulting in male sterility. To analyze the role of lncRNAs in pollen development, we conducted a comparative lncRNA sequencing using anthers from the male sterile mutant line (366–2 S) and the wild-type male fertile line (366–2 F). We identified 385 differentially expressed lncRNAs between the 366–2 F and 366–2 S lines, with 172 of them potentially associated with target genes. To further understand the alterations in mRNA expression and explore potential lncRNA-target genes (mRNAs), we performed comparative mRNA transcriptome analysis in the anthers of 366–2 S and 366–2 F at two stages. We identified 1,176 differentially expressed mRNAs. Remarkably, GO analysis revealed significant enrichment in five GO terms, most notably involving mRNAs annotated as pectinesterase and polygalacturonase, which play roles in cell wall degradation. The considerable downregulation of these genes might contribute to the delayed degradation of tapetum in 366–2 S. Furthermore, we identified 15 lncRNA-mRNA modules through Venn diagram analysis. Among them, MSTRG.9997-BraA04g004630.3 C (β-1,3-glucanase) is associated with callose degradation and tetrad separation. Additionally, MSTRG.5212-BraA02g040020.3 C (pectinesterase) and MSTRG.13,532-BraA05g030320.3 C (pectinesterase) are associated with cell wall degradation of the tapetum, indicating that these three candidate lncRNA-mRNA modules potentially regulate pollen development. Conclusion This study lays the foundation for understanding the roles of lncRNAs in pollen development and for elucidating their molecular mechanisms in regulating male sterility in Chinese cabbage.

Macrophages are central to the immune system and are found in nearly all tissues. Recently, the development of therapies based on macrophages has attracted significant interest. These therapies utilize macrophages' key roles in immunity, their ability to navigate biological barriers, and their tendency to accumulate in tumors. This review explores the advancement of macrophage-based treatments. We discuss the bioengineering of macrophages for improved anti-tumor effects, the use of CAR macrophage therapy for targeting cancer cells, and macrophages as vehicles for therapeutic delivery. Additionally, we examine engineered macrophage products, like extracellular vesicles and membrane-coated nanoparticles, for their potential in precise and less toxic tumor therapy. Challenges in moving these therapies from research to clinical practice are also highlighted. The aim is to succinctly summarize the current status, challenges, and future directions of engineered macrophages in cancer therapy.

Post-industrial regeneration, the conversion and integration of brown lands into green spaces, has become a prevalent process in contemporary urban sustainable development. Previous research on post-industrial landscapes has mostly focused on qualitative studies and paid little attention to the visual and physical attributes of these landscapes, providing little quantitative analyses of their physical qualities. We examined the relationship between landscape characteristics and individual perceptions and preferences of post-industrial landscapes. We used statistical modeling, including multivariate stepwise regression models, to involve the multidimensional integration of participants’ physiological responses, eye-tracking responses, and mental activity data. We found: 1) The hypothesis that “coherence and legibility may not serve as mediating factors in the relationship between low-level image features and preference as well as positive perception“ has been rejected. 2) The post-industrial landscape has unique aesthetic features of “Original – New Placement”. In this study, participants preferred artificial to natural scenes. 3) The significant factors in enhancing participants’ perceptions and preferences were the increase in the percentages of industrial remains, new construction, and ground-covering plants elements. 4) The type of artificial views in the post-industrial landscape has been positively influenced by the sense of industrial historical atmosphere and the sense of aesthetic appeal for industrial remains. 5) The percentage of water in post-industrial waterfront environments might reduce participants’ initial attraction to industrial remains in their original location. In application, these findings could help improve public preference and satisfaction in the design of post-industrial landscapes.

Abstract Background Neovascular eye disease is characterized by pathological neovascularization, with clinical manifestations such as intraocular exudation, bleeding, and scar formation, ultimately leading to blindness in millions of individuals worldwide. Pathologic ocular angiogenesis often occurs in common fundus diseases including proliferative diabetic retinopathy (PDR), age-related macular degeneration (AMD), and retinopathy of prematurity (ROP). Anti-vascular endothelial growth factor (VEGF) targets the core pathology of ocular angiogenesis. Main body In recent years, therapies targeting metabolism to prevent angiogenesis have also rapidly developed, offering assistance to patients with a poor prognosis while receiving anti-VEGF therapy and reducing the side effects associated with long-term VEGF usage. Phosphofructo-2-kinase/fructose-2,6-bisphosphatase 3 (PFKFB3), a key enzyme in targeted metabolism, has been shown to have great potential, with antiangiogenic effects and multiple protective effects in the treatment of neovascular eye disease. In this review, we summarize the mechanisms of common types of neovascular eye diseases; discuss the protective effect and potential mechanism of targeting PFKFB3, including the related inhibitors of PFKFB3; and look forward to the future exploration directions and therapeutic prospects of PFKFB3 in neovascular eye disease. Conclusion Neovascular eye disease, the most common and severely debilitating retinal disease, is largely incurable, necessitating the exploration of new treatment methods. PFKFB3 has been shown to possess various potential protective mechanisms in treating neovascular eye disease. With the development of several drugs targeting PFKFB3 and their gradual entry into clinical research, targeting PFKFB3-mediated glycolysis has emerged as a promising therapeutic approach for the future of neovascular eye disease.

Abstract Background In recent years, the development of adjunctive therapeutic hyperthermia for cancer therapy has received considerable attention. However, the mechanisms underlying hyperthermia resistance are still poorly understood. In this study, we investigated the roles of cold‑inducible RNA binding protein (Cirbp) in regulating hyperthermia resistance and underlying mechanisms in nasopharyngeal carcinoma (NPC). Methods CCK-8 assay, colony formation assay, tumor sphere formation assay, qRT-PCR, Western blot were employed to examine the effects of hyperthermia (HT), HT + oridonin(Ori) or HT + radiotherapy (RT) on the proliferation and stemness of NPC cells. RNA sequencing was applied to gain differentially expressed genes upon hyperthermia. Gain-of-function and loss-of-function experiments were used to evaluate the effects of RNAi-mediated Cirbp silencing or Cirbp overexpression on the sensitivity or resistance of NPC cells and cancer stem-like cells to hyperthermia by CCK-8 assay, colony formation assay, tumorsphere formation assay and apoptosis assay, and in subcutaneous xenograft animal model. miRNA transient transfection and luciferase reporter assay were used to demonstrate that Cirbp is a direct target of miR-377-3p. The phosphorylation levels of key members in ATM-Chk2 and ATR-Chk1 pathways were detected by Western blot. Results Our results firstly revealed that hyperthermia significantly attenuated the stemness of NPC cells, while combination treatment of hyperthermia and oridonin dramatically increased the killing effect on NPC cells and cancer stem cell (CSC)‑like population. Moreover, hyperthermia substantially improved the sensitivity of radiation‑resistant NPC cells and CSC‑like cells to radiotherapy. Hyperthermia noticeably suppressed Cirbp expression in NPC cells and xenograft tumor tissues. Furthermore, Cirbp inhibition remarkably boosted anti‑tumor‑killing activity of hyperthermia against NPC cells and CSC‑like cells, whereas ectopic expression of Cirbp compromised tumor‑killing effect of hyperthermia on these cells, indicating that Cirbp overexpression induces hyperthermia resistance. ThermomiR-377-3p improved the sensitivity of NPC cells and CSC‑like cells to hyperthermia in vitro by directly suppressing Cirbp expression. More importantly, our results displayed the significantly boosted sensitization of tumor xenografts to hyperthermia by Cirbp silencing in vivo, but ectopic expression of Cirbp almost completely counteracted hyperthermia-mediated tumor cell-killing effect against tumor xenografts in vivo. Mechanistically, Cirbp silencing-induced inhibition of DNA damage repair by inactivating ATM-Chk2 and ATR-Chk1 pathways, decrease in stemness and increase in cell death contributed to hyperthermic sensitization; conversely, Cirbp overexpression-induced promotion of DNA damage repair, increase in stemness and decrease in cell apoptosis contributed to hyperthermia resistance. Conclusion Taken together, these findings reveal a previously unrecognized role for Cirbp in positively regulating hyperthermia resistance and suggest that thermomiR-377-3p and its target gene Cirbp represent promising targets for therapeutic hyperthermia.

The effluent from the secondary sedimentation tank of the wastewater treatment plant of a liquor production enterprise in Guizhou was taken as the research object. Zero-valent iron（Fe0） activated persulfate（S2O82-，PS） advanced oxidation method was used to further treat the effluent，and the process conditions were optimized. The effects of initial pH，PS dosage and molar ratio of Fe0 to PS on the treatment effect of liquor wastewater were investigated by single factor experiment，and the process conditions were further optimized by response surface method. The results show that persulfate process can effectively reduce the organic content of liquor wastewater. The optimal process conditions are as follows：initial pH is 4.08，The PS dosage was 1.39 times the theoretical dosage （1 mg/L COD complete oxidation theoretically requires 12 mg/L PS），n（Fe0）∶n（PS）=1.27. Under these conditions，the COD removal rate of liquor wastewater reaches 70.33%.

The laser frequency stabilization technology is very important in the development of laser applications, and the improvement of this technology has tend to further expectations for portability and low cost, in addition to the realization of strict frequency control. In this context, we construct a dual-cavity laser frequency stabilization system based on an intracavity dual-mode self-reference mechanism. With this approach, we achieve remarkable results with a laser frequency drift of about 6.6 kHz and an Allen deviation (ADEV) of 10−13 levels over an integration time scale from 0.01 s to 1000 s. Notably, the solution achieves one of the best results without the need for an external reference structure. This work provides a way to realize wavelength-stabilized laser sources by interlocking two DFB lasers. This approach is distinguished by its simplicity and cost-effectiveness, making it a promising option for a variety of applications outside of the laboratory environment.

The stability of black rice anthocyanin microcapsules at high temperature, light and pH, and their release in simulated gastroenteric fluid were studied by emulsification and gelation of black rice anthocyanin microcapsules with calcium alginate as wall material. The stability of black rice anthocyanin in microcapsules prepared under the process parameters of sodium alginate concentration of 15 g/L, water oil volume ratio of 1∶3, wall to core ratio M (C3G)∶M (NaAlg) of 2∶1, and solution pH of 4.5 was significantly higher than that of uncoated free black ones under different pH, temperature, and light conditions. The microencapsulated anthocyanin could be kept for 4 hours in simulated gastric fluid, and the wall material was slowly decomposed and released in simulated intestinal fluid. The microencapsulation technology based on emulsified gel can improve the stability of anthocyanins, and achieve their intestinal delivery and sustained release in vivo.

Abstract Background Targeted drugs are not quite effective for prolonging the survival of patients with gastric cancer due to off-target effects as well as tumor immune escape mechanisms. Circular RNAs widely exist in tumor regions as biomarkers and can be developed as effective drug targets. Methods Western blot, QRT-PCR, fluorescence in situ hybridization, and flow cytometry were used to investigate the function of hsa_circ_0136666 in promoting the proliferation of gastric cancer cells. Tissue immunofluorescence, enzyme-linked immunosorbent assay (ELISA), as well as flow cytometric analysis, was conducted to explore the process of tumor immune evasion in tumor-bearing mice. The differences of circRNA expression in clinical samples were analyzed through tissue microarray FISH. The effect of siRNA on improving the efficacy of anti-PDL1 drugs and suppressing the immune microenvironment was evaluated by the coadministration model. Results We demonstrated that hsa_circ_0136666 was widely and highly expressed in gastric cancer tissues and cells. Functionally, hsa_circ_0136666 promoted gastric cancer tumor proliferation and tumor microenvironment formation, leading to tumorigenesis immune escape, and this effect was dependent on CD8 + T cells. Mechanistically, we confirmed that hsa_circ_0136666 competitively upregulated PRKDC expression by sponging miR-375-3p, regulating immune checkpoint proteins, prompting phosphorylation of PD-L1 to preventing its degradation, driving PD-L1 aggregation and suppressing immune function, thereby impairing cancer immune responses. In terms of application, we found that LNP-siRNA effectively improved anti-PDL1 drug efficacy and inhibited immune escape. Conclusion Our results reveal an oncogenic role played by hsa_circ_0136666 in gastric cancer, driving PD-L1 phosphorylation via the miR-375/PRKDC signaling axis, prompting immune escape. This work proposes a completely new pathogenic mechanism of gastric cancer, uncovers a novel role for hsa_circ_0136666 as an immune target, and provides a rationale for enhancing the efficacy of anti-PD-L1 therapy for gastric cancer.

Abstract Backgrounds Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease characterized by synovial hyperplasia. Maintaining a balance between the proliferation and apoptosis of rheumatoid arthritis synovial fibroblasts (RASFs) is crucial for preventing the erosion of bone and cartilage and, ultimately, mitigating the progression of RA. We found that the lncRNA LEF1-AS1 was expressed at low levels in the RASFs and inhibited their abnormal proliferation by targeting PIK3R2 protein and regulating the PI3K/AKT signal pathway through its interaction with miR-30-5p. In this study, we fabricated a nano-drug delivery system for LEF1-AS1 using Zn-Adenine nanoparticles (NPs) as a novel therapeutic strategy against RA. Methods The expression levels of LEF1-AS1, miR-30-5p, PIK3R2, p-PI3K, and p-AKT were detected in the primary RASFs and a human fibroblast-like synovial cell line (HFLS). Zn-Adenine nanoparticles (NPs) were functionalized with anti-CD305 antibody to construct (Zn-Adenine)@Ab. These NPs were then loaded with LEF1-AS1 to form (Zn-Adenine)@Ab@lncRNA LEF1-AS1. Finally, the (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs were locally injected into a rat model with collagen-induced arthritis (CIA). The arthritic injuries in each group were evaluated by HE staining and other methods. Results LEF1-AS1 was expressed at low levels in the primary RASFs. High expression levels of LEF1-AS1 were detected in the HFLS cells, which corresponded to a significant downregulation of miR-30-5p. In addition, the expression level of PIK3R2 was significantly increased, and that of p-PI3K and p-AKT were significantly downregulated in these cells. The (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly inhibited the proliferation of RASFs and decreased the production of inflammatory cytokines (IL-1β, IL-6, TNF-α). Intra-articular injection (IAI) of (Zn-Adenine)@Ab@lncRNA LEF1-AS1 NPs significantly alleviated cartilage destruction and joint injury in the CIA-modeled rats. Conclusions LEF1-AS1 interacts with miR-30-5p to inhibit the abnormal proliferation of RASFs by regulating the PI3K/AKT signal pathway. The (Zn-Adenine)@Ab NPs achieved targeted delivery of the loaded LEF1-AS1 into the RASFs, which improved the cellular internalization rate and therapeutic effects. Thus, LEF1-AS1 is a potential target for the treatment of RA.

AbstractContext Ginsenoside metabolite compound K (CK) is an active metabolite produced by ginsenosides in vivo that has an anti-arthritic effect related to the glucocorticoid receptor (GR). However, the potential mechanisms of CK remain unclear.Objective This study explores the role and potential mechanisms of CK in vivo and in vitro.Materials and methods Adjuvant arthritis (AA) model was induced in Sprague-Dawley (SD) rats; the rats were randomly divided into four groups (n = 10): normal, AA, CK (80 mg/kg), and dexamethasone (Dex) group (1 mg/kg). From day 15, rats were treated with CK (once a day, i.g.) and Dex (once every 3 days, i.p.) for 18 days. To further verify the mechanism of CK, fibroblast-like synoviocytes (FLS) were stimulated by tumour necrosis factor α (TNF-α) to establish an inflammatory model in vitro.Results CK (80 mg/kg) reduced paw swelling (52%) and arthritis global assessment (31%) compared to that in AA rats. In addition, CK (80 mg/kg) suppressed GLUT1 (38%), HK2 (50%), and PKM2 (56%) levels compared with those in AA FLS. However, the effects of CK (30 μM) on these events were weakened or enhanced after GR knockdown or overexpression in FLS stimulated by TNF-α (30 ng/mL). CK (80 mg/kg) also downregulated the expression of P65 (61%), p-IκB (92%), and HIF-1α (59%).Discussion and conclusions The inhibition of CK on glycolysis and the NF-κB/HIF-1α pathway is potentially mediated through activating GR. These findings provide experimental evidence for elucidating the molecular mechanism of CK in treating rheumatoid arthritis (RA).

Chinese cabbage (Brassica rapa L. ssp. pekinensis) ranks among the most cultivated and consumed vegetables in China. A major threat to its production is Plasmodiophora brassicae, which causes large root tumors, obstructing nutrient and water absorption and resulting in plant withering. This study used a widely targeted metabolome technique to identify resistance-related metabolites in resistant (DH40R) and susceptible (DH199S) Chinese cabbage varieties after inoculation with P. brassicae. This study analyzed disease-related metabolites during different periods, identifying 257 metabolites linked to resistance, enriched in the phenylpropanoid biosynthesis pathway, and 248 metabolites linked to susceptibility, enriched in the arachidonic acid metabolism pathway. Key metabolites and genes in the phenylpropanoid pathway were upregulated at 5 days post-inoculation (DPI), suggesting their role in disease resistance. In the arachidonic acid pathway, linoleic acid and gamma-linolenic acid were upregulated at 5 and 22 DPI in resistant plants, while arachidonic acid was upregulated at 22 DPI in susceptible plants, leading to the conclusion that arachidonic acid may be a response substance in susceptible plants after inoculation. Many genes enriched in these pathways were differentially expressed in DH40R and DH199S. The research provided insights into the defense mechanisms of Chinese cabbage against P. brassicae through combined metabolome and transcriptome analysis.

Arundo donax (family: Poaceae) is a perennial rhizomatous plant with considerable economic and ecological benefits. The plant is characterized by its fast growth, high yield, wide adaptability, and strong disease resistance. However, widespread cultivation is difficult because A. donax can only be asexually propagated. This study tested the efficacy of an aqua-based culture method with short duration and high rooting rate. The aqua-based culture protocol involved treating cane fragments with the commercial broad-spectrum rooting powder ABT-1 (No. 1 of the ABT series) at 100 mg/L for 24 h, followed by culturing in tap water for 19 days. We found that plant materials sampled from September to February of the following year were more suitable for aqua-based culturing than materials sampled from other months. Nodes on different parts of the cane did not vary significantly in the ability to form seedlings. The rooting percentage reached >95% after only 20 days, while the sprouting percentage was >93%. The seedlings obtained were strong, with high survival rates during cultivation and acclimation. No strict requirements for the growing media were necessary to achieve these results. In conclusion, this study provides an empirical foundation for a technique that could facilitate the factory production of high-quality A. donax seedlings.

Objective To compare the effectiveness of anterior cervical discectomy and fusion (ACDF) and anterior cervical corpectomy and fusion (ACCF) in the treatment of twolevel cervical spondylotic myelopathy. Methods Clinical data of 58 patients with two-level cervical spondylotic myelopathy treated from January 2020 to December 2022 at Nanjing Jiangbei Hospital Affiliated to Xinglin College, Nantong University were retrospectively analyzed. Patients were divided into ACDF group (n=30) and ACCF group (n=28) based on the surgical procedure. Perioperative data (hospitalization time, intraoperative blood loss and operation time), clinical parameters ［neck disability index (NDI) score and visual analog scale (VAS) score］, and imaging data (segmental angle, T1 slope, C 2-7sagittal vertical axis, C 2-7cervical lordosis, and fusion rate) were compared between the two groups. Results The operation time ［（107.38±12.29）min vs (118.37±11.36)min, t=3.529, P＜0.01］ and intraoperative blood loss ［（58.36±24.31）mL vs （77.73±27.51）mL, t=2.846, P＜0.01］ were lower in the ACDF group than in the ACCF group. Both groups showed significantly decreased NDI and VAS scores postoperatively compared to preoperative scores (P＜0.05), but the difference between the two groups was not statistically significant (P＞0.05). The ACDF group showed significant improvements in segmental angle and C 2-7cervical lordosis postoperatively and at the last follow-up, which were greater than those in the ACCF group (P＜0.05). There was no statistically significant difference in T1 slope, C 2-7sagittal vertical, and fusion rate between the two groups (P＞0.05). Conclusion In the treatment of two-level cervical spondylotic myelopathy, ACDF has less surgical trauma than ACCF and is more advantageous in restoring cervical lordosis. For cases without significant bony spinal cord compression, ACDF is a preferable surgical option for two-level cervical spondylotic myelopathy.

Clubroot disease poses a significant threat to Brassica crops, necessitating ongoing updates on resistance gene sources. In F2 segregants of the clubroot-resistant inbred line BrT18-6-4-3 and susceptible DH line Y510, the genetic analysis identified a single dominant gene responsible for clubroot resistance. Through bulk segregant sequencing analysis and kompetitive allele-specific polymerase chain reaction assays, CRA8.1.6 was mapped within 110 kb (12,255–12,365 Mb) between markers L-CR11 and L-CR12 on chromosome A08. We identified B raA08g015220.3.5C as the candidate gene of CRA8.1.6. Upon comparison with the sequence of disease-resistant material BrT18-6-4-3, we found 249 single-nucleotide polymorphisms, seven insertions, six deletions, and a long terminal repeat (LTR) retrotransposon (5,310 bp) at 909 bp of the first intron. However, the LTR retrotransposon was absent in the coding sequence of the susceptible DH line Y510. Given the presence of a non-functional LTR insertion in other materials, it showed that the LTR insertion might not be associated with susceptibility. Sequence alignment analysis revealed that the fourth exon of the susceptible line harbored two deletions and an insertion, resulting in a frameshift mutation at 8,551 bp, leading to translation termination at the leucine-rich repeat domain’s C-terminal in susceptible material. Sequence alignment of the CDS revealed a 99.4% similarity to Crr1a, which indicate that CRA8.1.6 is likely an allele of the Crr1a gene. Two functional markers, CRA08-InDel and CRA08-KASP1, have been developed for marker-assisted selection in CR turnip cultivars. Our findings could facilitate the development of clubroot-resistance turnip cultivars through marker-assisted selection.

Objective Primary Sjögren’s syndrome (pSS) is the second most common chronic autoimmune connective tissue disease. Autoantibodies, immunoglobulin (IgG) anti-SSA/Ro, in serum is a key diagnostic feature of pSS. Since pSS is a disease of the salivary gland, we investigated anti-SSA/Ro52 in saliva.Methods Using a novel electrochemical detection platform, Electric Field-Induced Release and Measurement, we measured IgG/M/A, IgG, IgA, IgA isotypes (IgA1 and IgA2) and IgA1 subclasses (polymeric and monomeric IgA1) to anti-SSA/Ro52 in saliva supernatant of 34 pSS, 35 dry eyes and dry mouth (patients with Sicca) and 41 health controls.Results Saliva IgG/M/A, IgG, IgA, IgA isotypes and IgA1 subclasses to anti-SSA/Ro52 differed significantly between pSS, non-pSS Sicca and healthy subjects. Elevated monomeric IgA1 was observed in patients with non-pSS Sicca while elevated polymeric IgA1 (pIgA1) was observed in patients with pSS. Salivary polymeric but not monomeric IgA1 (mIgA1) isoform correlated with focus score (r2=0.467, p=0.001)Conclusions Salivary anti-Ro52 polymeric IgA1 isoform is associated with glandular inflammation in pSS, while salivary monomeric IgA1 is associated with Sicca. Whether IgA1 isotope switching plays a role in the progression of the Sicca to pSS warrants further investigation.

Abstract Background Breast cancer remains a global health challenge, necessitating innovative therapeutic approaches. Immunomodulation and immunotherapy have emerged as promising strategies for breast cancer treatment. Engineered exosomes are the sort of exosomes modified with surface decoration and internal therapeutic molecules. Through suitable modifications, engineered exosomes exhibit the capability to overcome the limitations associated with traditional therapeutic approaches. This ability opens up novel avenues for the development of more effective, personalized, and minimally invasive interventions. Main body In this comprehensive review, we explore the molecular insights and therapeutic potential of engineered exosomes in breast cancer. We discuss the strategies employed for exosome engineering and delve into their molecular mechanisms in reshaping the immune microenvironment of breast cancer. Conclusions By elucidating the contribution of engineered exosomes to breast cancer immunomodulation, this review underscores the transformative potential of this emerging field for improving breast cancer therapy. Highlights Surface modification of exosomes can improve the targeting specificity. The engineered exosome‐loaded immunomodulatory cargo regulates the tumour immune microenvironment. Engineered exosomes are involved in the immune regulation of breast cancer.

BackgroundIn China, most of the citizens experienced SARS-CoV-2 infection since the end of 2022. The Coronavirus disease 2019 (COVID-19) pandemic affected people’s physical health and also had a significant impact on mental well-being. The present study aims to discover if the experience of SARS-CoV-2 infection influences patients’ anxiety toward third molar surgery in the Chinese population.Materials and methodsThe present study took the form of a questionnaire survey. From January 1, 2023, to June 30, 2023, patients who went to the Stomatology Center of China-Japan Friendship Hospital (Beijing, China) for the third molar extraction were included according to the inclusion criteria. The information on COVID-19 infection and the Modified Dental Anxiety Scale (MDAS) was collected. The software SPSS 22.0 was used for the statistical analyses.ResultsA total of 574 survey results were harvested in the present study. The infection rate of COVID-19 was 86.6% (p > 0.05). The Average MDAS scores between patients who had been infected with COVID-19 and patients who were never infected were not significantly different (11.65 ± 4.41 vs. 11.42 ± 4.41, p > 0.05). The subgroup analysis was conducted according to the length of time after the recovery of COVID-19 (Model 1), and the highest temperature during the infection (Model 2). In Model 1 and Model 2, the one-way ANOVA test did not find statistical significance between the groups (Model 1 p = 0.114; Model 2 p = 0.481). The MDAS scores in female patients were significantly higher than in male patients (12.29 ± 4.53 vs. 9.91 ± 3.80, p

Abstract Background The Forkhead box M1 factor (FOXM1) is a crucial activator for cancer cell proliferation. While FOXM1 has been shown to promote hepatocellular carcinoma (HCC) progression, its transcriptional mechanisms remain incompletely understood. Methods We performed an in-house tissue microarray on 313 HCC and 37 non-HCC tissue samples, followed by immunohistochemical staining. Gene chips and high throughput sequencing data were used to assess FOXM1 expression and prognosis. To identify candidate targets of FOXM1, we comprehensively reanalyzed 41 chromatin immunoprecipitation followed by sequencing (ChIP-seq) data sets. We predicted FOXM1 transcriptional targets in HCC by intersecting candidate FOXM1 targets with HCC overexpressed genes and FOXM1 correlation genes. Enrichment analysis was employed to address the potential mechanisms of FOXM1 underlying HCC. Finally, single-cell RNA sequencing analysis was performed to confirm the transcriptional activity of FOXM1 on its predicted targets. Results This study, based on 4235 HCC tissue samples and 3461 non-HCC tissue samples, confirmed the upregulation of FOXM1 in HCC at mRNA and protein levels (standardized mean difference = 1.70 [1.42, 1.98]), making it the largest multi-centered study to do so. Among HCC patients, FOXM1 was increased in Asian and advanced subgroups, and high expression of FOXM1 had a strong ability to differentiate HCC tissue from non-HCC tissue (area under the curve = 0.94, sensitivity = 88.72%, specificity = 87.24%). FOXM1 was also shown to be an independent exposure risk factor for HCC, with a pooled hazard ratio of 2.00 [1.77, 2.26]. The predicted transcriptional targets of FOXM1 in HCC were predominantly enriched in nuclear division, chromosomal region, and catalytic activity acting on DNA. A gene cluster encoding nine transcriptional factors was predicted to be positively regulated by FOXM1, promoting the cell cycle signaling pathway in HCC. Finally, the transcriptional activity of FOXM1 and its targets was supported by single-cell analysis of HCC cells. Conclusions This study not only confirmed the upregulation of FOXM1 in HCC but also identified it as an independent risk factor. Moreover, our findings enriched our understanding of the complex transcriptional mechanisms underlying HCC pathogenesis, with FOXM1 potentially promoting HCC progression by activating other transcription factors within the cell cycle pathway.

Abstract Objective To analyze factors influencing the underestimation of noise-induced permanent threshold shift (NIPTS) among manufacturing workers, providing baseline data for revising noise exposure standard. Design A cross-sectional study was designed with 2702 noise-exposed workers from 35 enterprises from 10 industries. Personal noise exposure level(L Aeq,8h ) and noise kurtosis level were determined by a noise dosimeter. Questionnaires and hearing loss tests were performed for each subject. The predicted NIPTS was calculated using the ISO 1999:2013 model for each participant, and the actual measured NIPTS was corrected for age and sex. The factors influencing the underestimation of NIPTS were investigated. Results The predicted NIPTS at each test frequency (0.5, 1, 2, 3, 4, or 6kHz) and mean NIPTS at 2, 3, 4, and 6kHz (NIPTS2346) using the ISO 1999:2013 model were significantly lower than their corresponding measured NIPTS, respectively (P 90 dB(A)]. The underestimated NIPTS2346 increased with an increase in noise kurtosis after adjusting for the noise exposure level and exposure duration and ultimately exhibiting a linear regression relationship. Conclusions The ISO 1999 predicting model significantly underestimated the noise-induced hearing loss among manufacturing workers. The degree of underestimation became more significant at the noise exposure condition of fewer than ten years, less than 90 dB(A), and higher kurtosis levels. It is necessary to apply kurtosis to adjust the underestimation of hearing loss and consider the applying condition of noise energy metrics when using the ISO predicting model.

Abstract Background Recent advances in circulating cell-free DNA (cfDNA) analysis from biofluids have opened new avenues for liquid biopsy (LB). However, current cfDNA LB assays are limited by the availability of existing information on established genotypes associated with tumor tissues. Certain cancers present with a limited list of established mutated cfDNA biomarkers, and thus, nonmutated cfDNA characteristics along with alternative biofluids are needed to broaden the available cfDNA targets for cancer detection. Saliva is an intriguing and accessible biofluid that has yet to be fully explored for its clinical utility for cancer detection. Methods In this report, we employed a low-coverage single stranded (ss) library NGS pipeline “Broad-Range cell-free DNA-Seq” (BRcfDNA-Seq) using saliva to comprehensively investigate the characteristics of salivary cfDNA (ScfDNA). The identification of cfDNA features has been made possible by applying novel cfDNA processing techniques that permit the incorporation of ultrashort, ss, and jagged DNA fragments. As a proof of concept using 10 gastric cancer (GC) and 10 noncancer samples, we examined whether ScfDNA characteristics, including fragmentomics, end motif profiles, microbial contribution, and human chromosomal mapping, could differentiate between these two groups. Results Individual and integrative analysis of these ScfDNA features demonstrated significant differences between the two cohorts, suggesting that disease state may affect the ScfDNA population by altering nuclear cleavage or the profile of contributory organism cfDNA to total ScfDNA. We report that principal component analysis integration of several aspects of salivary cell-free DNA fragmentomic profiles, genomic element profiles, end-motif sequence patterns, and distinct oral microbiome populations can differentiate the two populations with a p value of

Abstract MOFs have considerable adsorption capacity due to their huge specific surface area. They have the characteristics of photocatalysts for their organic ligands can absorb photons and produce electrons. In this paper, the photodegradation properties of TiO2 composites loaded with UiO-66 were investigated for the first time for MO. A series of TiO2@UiO-66 composites with different contents of TiO2 were prepared by a solvothermal method. The photocatalytic degradation of methyl orange (MO) was performed using a high-pressure mercury lamp as the UV light source. The effects of TiO2 loading, catalyst dosage, pH value, and MO concentration were investigated. The results showed that the degradation of MO by TiO2@UiO-66 could reach 97.59% with the addition of only a small amount of TiO2 (5 wt%). TiO2@UiO-66 exhibited significantly enhanced photoelectron transfer capability and inhibited efficient electron–hole recombination compared to pure TiO2 in MO degradation. The composite catalyst indicated good stability and reusability when they were recycled three times, and the photocatalytic reaction efficiencies were 92.54%, 88.76%, and 86.90%. The results provide a new option to design stable, high-efficiency MOF-based photocatalysts.

Arundo donax is widely used as an ornamental plant in landscape gardening because of its adaptability to varying degrees of waterlogged conditions. However, to date, little information is available about the adaptive mechanism of A. donax under waterlogging stress. The results showed that long-term mild waterlogging efficiently induced the formation of adventitious roots (ARs) and further promoted root aerenchyma development, and that the activity of antioxidant enzymes (SOD, POD, and CAT) in Ars also was greatly enhanced after waterlogging. At the transcriptomic level, the expression of genes related to apoptosis, the regulation of cell division, ethylene biosynthesis, alginate synthesis, auxin signaling pathways, and anaerobic respiration was mostly up-regulated after the occurrence of waterlogging stress but genes involved in the abscisic acid signaling pathways were partly down-regulated, which indicated a preferential and favorable transcriptional response in regulating adventitious root development. Taken together, this study definitely advances our knowledge of the morphological, physiological, and transcriptomic responses of A. donax under waterlogging stress and sheds new lights on its adaptive mechanisms.

Abstract Objective To determine the efficacy of cataract surgeries in blindness prevention programs in Chongqing. Methods During February–December 2019, we prospectively enrolled 487 patients (592 eyes) undergoing cataract surgery during blindness prevention programs in 6 Chongqing district/county hospitals (experimental group) and 481 patients (609 eyes) undergoing cataract surgery in the First Affiliated Hospital of Chongqing Medical University (controls). Uncorrected visual acuity (UCVA), refractive status, best corrected visual acuity (BCVA), slit lamp examination, and visual function/quality of life (VF-QOL) questionnaire scores were evaluated preoperatively, and at 1 and 6 months postoperatively. Results In the experimental group, UCVA, BCVA, and VF-QOL scores at 1 and 6 months were better than the preoperative values (P 0.5 logMAR) in the experimental group were uncorrected refractive errors (33.0%), PCO (29.5%), and fundus diseases (33.9%). Conclusion Cataract surgeries in blindness prevention programs in Chongqing significantly improved visual acuity, VF, and QOL, but underperformed compared to surgeries in the tertiary teaching hospital.

In the face of a serious occupational disease prevention and control situation, the lack of efficient supervision and regulation methods has become a prominent contradiction. This paper reviewed the progress and application of occupational health grading and classification supervision methods for employers in China in recent years, and analyzed the characteristics and limitations of selected methods. The grading and classification supervision methods have gradually developed from considering only inherent health risk of occupational disease hazards, to considering both inherent attributes of occupational disease hazards and exposure duration. Some regional authorities introduced trial measures for grading and classification of occupational health supervision by embracing exposure level of an occupational disease hazard of interest, associated outcome severity, and occupational health management situation of targeted employers. In October 2022, the National Disease Control and Prevention Bureau issued the Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which further promoted the establishment of a differentiated occupational health supervision model. Grading and classification of occupational health supervision can improve the supervision efficiency of public health administration departments and promote employers to fulfill the main responsibility of occupational disease prevention and control.

The National Disease Control and Prevention Bureau and the National Health Commission jointly issued an announcement on Notice on Carrying out Pilot Work of Occupational Health Classification Supervision and Law Enforcement, which presented a method of comprehensive risk assessment method of occupational disease hazards of employers. This method embraces relevant factors at full scale and is simple in operation, but its applicability and accuracy of assessment results need further practical study. Based on the steps of occupational health risk assessment and proven occupational health risk assessment methods available at home and abroad, this paper proposed improvements and discussed the comprehensive risk assessment method of occupational disease hazards of employers, so as to provide a technical basis to implement the occupational disease hazard classification management of employers for relevant government supervision departments.

The study investigates the impact of steam explosion pretreatment on the distribution of free and combined phytosterols within rapeseed and its derived products. Utilizing solid phase extraction-gas chromatography (SPE-GC) analysis, we elucidated the composition and distribution of phytosterols in five rapeseed varieties and their corresponding processed oils and cakes. The results indicated that Zhongyou 516 and Xiwang 988 are richer in combined phytosterols, whereas Dadi 199, Zhongyouza 501, and Xiwang 291 have a greater concentration of free phytosterols. Steam explosion pretreatment significantly increased the extraction proportion of combined phytosterols in rapeseeds. Throughout the oil process, more than half of the total phytosterol content, specifically 57.0%, was transferred from the steam explosion-treated rapeseed into the rapeseed oil. The variety Xiwang 291 showed the highest efficiency in this transfer, achieving a rate of 61.7%. The study provides crucial data for the enhancement of rapeseed processing techniques and the efficient utilization of phytosterols. Moreover, the study highlights the potential use of the ratio of free to combined phytosterols as a discriminator for different rapeseed oil varieties, offering valuable insights for quality assurance and product differentiation in the industry.

Agricultural pests and diseases critically impact the quality and yield of crops, thereby underscoring the practical importance of their automatic monitoring, identification, and timely management in agricultural production. This study develops a targeted detection model using a deep learning approach, specifically by enhancing the Faster R-CNN algorithm. Modifications were implemented in three key areas of the basic Faster R-CNN: First, the DIOU-NMS technique was employed to optimize the ancillary network during the feature extraction phase. Secondly, an attention mechanism along with an SE module was integrated within the DIOU-NMS to augment the network’s capability. During the training phase, optimization was facilitated through stochastic gradient descent. The efficacy of the refined Faster RCNN model was established via ablation studies, and its performance was benchmarked against existing methodologies for small and general target detection. Results indicate that the enhanced Faster R-CNN framework surpasses conventional small target and generic detection models in accuracy, achieving a 6.4% higher detection rate for various pest categories compared to its predecessor. The findings affirm the potential of the advanced Faster R-CNN in effective agricultural pest detection. Furthermore, this paper advocates a tripartite strategy for pest management, encompassing phytosanitary measures, agricultural interventions, and chemical controls.

Urban green spaces shaped by the post-industrial landscape possess distinctive characteristics and aesthetic features due to the exceptional properties of industrial remains. Previous studies have indicated that various types of urban green spaces without industrial remains, such as urban parks, waterfronts, and streets, have a positive impact on the public's physiological and psychological well-being. However, the extent and mechanisms of the public's response to post-industrial landscapes remain unclear. To investigate mechanisms of public perceptions of and preferences for post-industrial landscape types and elements, we conducted quantitative analysis by coupling multimodal data and comparative or difference analyses among urban green spaces. We conducted a randomized controlled experiment with 48 participants who viewed images of different combinations of post-industrial landscapes in a distraction-free environment. After a pause, Positive-Negative perception and Preference questionnaires were completed. Eye tracking data were recorded during the experiment. Changes in electrodermal activity and heart rate variability were used to measure physiological stress. This study employed Pearson's correlation model to examine the relationships between objective data and subjective data. The ANOVA test was utilized to investigate the variability of objective and subjective data across different groups. Additionally, a multiple-stepwise regression model was employed to analyze the specific influencing factors and their respective degrees of influence. We found that (1) artificial landscape elements in post-industrial landscapes were more appealing to participants and heightened their sense of stress; natural landscape elements can alleviate stress and promote restoration. (2) The percentage of flowering shrub and tree elements was significantly positively correlated with preference, while the percentage of ground-covering plant elements was significantly negatively correlated with preference. (3) Industrial construction was significantly positively correlated with the sense of historical value while industrial construction and pavement elements negatively correlated with preference. However, pavement elements significantly mitigated the sense of insecurity, poor accessibility, and pollution risk. (4) Industrial construction and pavement distinguished the post-industrial landscape from other green spaces without industrial remains while maximizing historical value and curiosity helped increase positive effects. Although impact mechanisms of natural elements in other green spaces without industrial remains showed homogeneous similarities, the scene composed of industrial mixed with natural elements may lead to different perceptions. Our findings indicate that multimodal data coupled with comparative analysis of multiple green space types can help to fully identify mechanisms by which landscape types and elements influence public perceptions and preferences. This understanding can help increase public satisfaction with post-industrial landscapes and enable researchers to determine the sustainability of post-industrial sites using interrogative design.

BACKGROUND Human health is closely related to the geological environment. There’re various geological environment factors affecting human health in a composite way. Geological background characteristics, including tectonic structure, lithologic features, and landform configuration shape the living conditions of human being. Climate conditions and the spatial and temporal variation characteristics influence the comfortable level for habitation. More importantly, the direct and indirect impacts of elements and chemicals in rock, soil, water, and air and biosphere on human health are comprehensive and significant. In addition, various human activities have increasingly influenced geological substances and geological processes since the Industrial Revolution, which together with natural geological factors contribute to the unique public health characteristics of a region. (Fig.1). Quantifying the impact of geological environment on human health has always been a hot topic in the study of environment, geology, and other disciplines. In terms of environmental health impact assessment, many scholars or organizations have developed different evaluation indicator systems from different research perspectives. Existing studies focus on assessing health risks from a single perspective, such as chemical substances or engineering construction, while comprehensive evaluation of the health impact of the geological environment from the perspective of the earth system is still rare. In today’s world of rapid socio-economic development, the relationship between human health and geological environment is even more complex, and single methods of evaluating environmental and population health are increasingly inadequate to cope with the increasingly complex health factors. The study of the suitability of geological environment for human health is rapidly progressing under a new theoretical framework. RESULTS (1) The evaluation index system. A comprehensive geological environmental health suitability evaluation index system was developed based on a composite perspective, taking into account multiple dimensions such as environmental geochemistry, regional geological background, climate conditions, and intensity of human activities. The rock strata, topography, climate conditions, as well as the geochemical quality of multiple media such as soil, water, and crops in a certain area, shape the specific lifestyle and behavioral habits of the regional population, resulting in unique regional health characteristics. (2) GHI evaluation method. The geological health index (GHI) evaluation method was established, which divides the health suitability of regional geological environments into five grades based on GHI scores: excellent (85 points or above), good (75-85), fair (60-75), poor (50-60), and very poor, representing the conditions of extremely suitable, suitable, moderately suitable, possibly suitable, and unsuitable for human health. (3) Case study. A case study was conducted in Anji and Longyou counties of Zhejiang Province using the GHI method. The overall GHI scores of the two regions indicated that the health suitability of the geological environment in Anji county was rated as “good” (78.16), while Longyou county was rated as “excellent” (85.50). The evaluation results reflected the health suitability of the regional geological environment, and could provide guidance for rational utilization of geological resources beneficial to health and avoidance of geological risks adverse to health. DISCUSSION (1) Principles for choosing indicators. The assessment index system was established following scientific principles, making sure the indicators are representative for general geological environment and closely related to human health. The influence of each indicator on health should be based on evidence, which can objectively reflect the difference of geological environment on population health. Furthermore, the indicators should be available in most settings and be simple to calculate. It is beneficial to have the current environmental industry or health industry standards as a reference. (2) Composition of the index system. The GHI index system included 15 specific indicators, which were listed in Table 1. Four sub-indexes were classified to represent the influencing factors of geological environment on human health, which were climate, geological background, environmental geochemistry characteristics and human activities. Two indicators of human comfort level, representing integrated influence of air temperature, humidity and wind, and incidence of extreme weather, were used to characterize the climate factors that affect human health. Four indicators, including regional crustal stability, natural environmental radioactivity, altitude and vegetation coverage, which were closely related to population health, were extracted to characterize the suitability of spatial characteristics of structure, rock, strata and epigenetic systems to population health. Seven indicators including environmental air quality, drinking water quality, irrigation water quality, cultivated land soil quality, agricultural product quality, water resource quantity and land resource quantity were used to characterize the environmental geochemical elements that have an important impact on population health. Human activities have influenced and changed the natural substances at global and regional scales, which have brought about significant impacts on the survival of organisms and human health. In this study, population density and per capita gross industrial and agricultural product were used to characterize the intensity of human activities. (3) GHI evaluation method. The evaluation of the health suitability of the geological environment was performed following the processes of data standardization, weight assignment, index score calculation and evaluation level classification. A two-step method was proposed to standardize data processing to complete the evaluation process of health suitability of the geological environment. Firstly, the environmental quality level corresponding to all indicators was determined by comparing with the national average level, national and industrial standards and specifications. Secondly, the impact of different levels of geological environmental quality on population health was evaluated with reference to literature, world and national health standards, and the degree of impact is measured with 0-100 points. The weights were assigned to each indicator according to analytic hierarchy procedure (AHP). The scores of each sub-index and total GHI index were calculated according to corresponding equation. Finally, the health suitability of regional geological environment is divided into five levels: excellent (85 points and above), good (75-85), general (60-75), poor (50-60) and bad (below 50), which respectively represent the state of extremely suitable, suitable, relatively suitable, possibly suitable and unsuitable to population health in certain regional geological environment. (4) Case study. A case study was conducted in Anji and Longyou counties of Zhejiang Province using the GHI method. The results showed that the two regions scored similarly in the three sub-indices of “climate conditions”, “geological background”, and “human activity intensity”, while there was a significant difference in the sub-index of “environmental geochemistry”. This was because the agricultural products in the selenium-enriched area of Anji were severely contaminated with heavy metals, while there was no such phenomenon in the selenium-enriched land of Longyou County. The overall GHI scores of the two regions indicated that the health suitability of the geological environment in Anji county was rated as “good” (78.16), while Longyou County was rated as “excellent” (85.50). However, the investigation found little difference in the health status of the residents in the two areas, with the average life expectancy of the residents in both areas higher than the national average. This suggests that although the geological environment in Anji County has high geochemical characteristics of Cd and Ni, the selenium-enriched environment has played a certain compensatory role, and Anji County still maintains an overall level of “suitable” for human health. (5) Limitations and future research prospects. With the rapid development of global society and economy, the relationship between population health and geological environment is complicated, and the evaluation method with single dimension is difficult to adapt to the increasingly complicated situation of health influencing factors. In this study, the GHI method is proposed to evaluate the health suitability of geological environment. Based on the multi-dimension of environmental geochemistry, regional geological background, climate condition and human activity intensity, the evaluation index system and evaluation method of geological environmental health suitability are studied from a composite perspective. The GHI evaluation method could be used for regional geological environment evaluation and zoning, and the evaluation results could help manage a more habitable environment and improve the health level of the population. However, there are still some limitations to this approach: ①There is no grouping of the target population. ②The exposure time is not considered. ③The actual intake of water and food is not confirmed. To sum up, the method will be continuously improved by refining the index system, to develop a health suitability assessment method with greater spatial heterogeneity that could meet the needs of the public and government to the greatest extent.

Abstract Background It is unclear whether excessive salt intake accelerates the progression of cerebral small vessel disease (CSVD). The major objective of this study was to investigate the harmful effect of excessive salt intake on the progression of CSVD in older individuals. Methods Between May 2007 and November 2010, 423 community-dwelling individuals aged 60 years and older were recruited from the Shandong area, China. Salt intake was estimated using 24-hour urine collection for 7 consecutive days at baseline. Participants were classified into low, mild, moderate and high groups according to the salt intake estimation. CSVD including white matter hyperintensities (WMHs), lacunes, microbleeds and an enlarged perivascular space (EPVS) were determined using brain magnetic resonance imaging. Results During an average of five years of follow-up, the WMH volume and WMH-to-intracranial ratio were increased in the four groups. However, the increasing trends in the WMH volume and WMH-to-intracranial ratio were significantly faster in the higher salt intake groups compared with the lower salt intake groups (P adjusted < 0.001). The cumulative hazard ratios of new-incident WMHs (defined as those with Fazekas scale scores ≥ 2), new-incident lacunes, microbleeds or an EPVS, as well as composites of CSVD, were respectively 2.47, 2.50, 3.33, 2.70 and 2.89 for the mild group; 3.72, 3.74, 4.66, 4.01 and 4.49 for the moderate group; and 7.39, 5.82, 7.00, 6.40 and 6.61 for the high group, compared with the low group after adjustment for confounders (P adjusted < 0.001). The risk of new-incident WMHs, lacunes, microbleeds or an EPVS, and composites of CSVD was significantly increased with each 1-standard-deviation increment in salt intake (P adjusted < 0.001). Conclusion Our data indicates that excessive salt intake is an important and independent contributor to the progression of CVSD in older adults.

To optimize the gas transfer, adsorption and photo-generated charge separation in the process of photocatalytic CO2 reduction by g-C3N4, the photocatalytic materials were designed from the aspects of foam pore structure and heterojunction construction. The typical g-C3N4 foam was first constructed using surfactant foaming method, and then Cu(OH)2 nanosheets were loaded to prepare the Cu(OH)2/CNF composites with projects of electroless copper plating and hydrogen oxidation treatment. The structure and photocatalytic properties of the as-prepared samples were investigated. The results show that g-C3N4 foam and Cu(OH)2/CNF all demonstrate developed structures with 3D micron pore frameworks, which is conducive to improving CO2 diffusion and adsorption at dynamics during gas-solid catalytic process. The adsorption amounts of CO2 for g-C3N4 foam and Cu(OH)2/CNF are respectively 3.97 cm3/g and 3.59 cm3/g, which are 2.96 times and 2.68 times respectively higher than that of pure g-C3N4 powder. Moreover, many Cu(OH)2 nanosheets are also formed in the Cu(OH)2/CNF samples which provide a way to simultaneously broaden light absorption and form heterojunction between g-C3N4 and Cu(OH)2. This heterojunction can accelerate the separation of photo-generated e--h+ and make photo-generated electrons transfer from g-C3N4 to Cu(OH)2. As a result, the Cu(OH)2/CNF has demonstrated optimal photocatalytic activity with CO production rate at 11.041 μmol·g-1·h-1, which is 2.76 times and 6.83 times respectively higher than that of g-C3N4 foam and g-C3N4 powder.

Food provides abundant nutrients for human beings, but also has sensory functions and physiological regulation. Lipids are the main components of food as well as the important structural and functional components of cells. Nevertheless, lipids are easily oxidized by different ways, such as thermal oxidation and air oxidation. Lipid oxidation has adverse effects on food quality and human health. Therefore, efforts should be made to reduce lipid oxidation and improve its stability. This review focuses on important knowledge about lipid oxidation, including the concept of lipids and lipid oxidation, the main pathways and mechanisms of lipid oxidation, factors affecting lipid oxidation, strategies to improve the stability of lipid oxidation, and the recent research progress of lipid oxidation in food science and nutritional health.

DHA-enriched eggs have gained popularity due to their unique nutritional value, but their flavor can be challenging for some consumers to accept. The study analyzed the correlation of lipids and flavors in DHA-enriched egg yolks using comprehensive lipidomics and volatile compound analysis. The results showed that 411 lipids were detected in two egg yolk samples. Among them, 148 lipid species, including 48 DHA-containing lipids, were significantly higher in DHA-enriched egg yolks than in Common ones (P ​

This study investigated the incorporation of nervonic acid into the chemical structure of phosphatidylcholine via a lipase-catalyzed acidolysis reaction to obtain a functional phospholipid. Lipase immobilization was conducted, and Amberlite XAD7-HP was selected as a carrier to immobilize phospholipase A1 (PLA1) for subsequent experiments. The main acidolysis reaction parameters, including enzyme load, substrate ratio, temperature, and water content, were studied against the reaction time. The optimum reaction conditions obtained were enzyme load, 20%; reaction temperature, 55 °C; water content, 1%; and reaction time, 9 h. The maximum incorporation of nervonic acid into phosphatidylcholine was 48 mol%, with PC recovery at 61.6 mol%. The positional distribution of structured phosphatidylcholine shows that nervonic acid was found in the sn-1 position due to enzyme specificity and in the sn-2 position, possibly due to acyl migration.

ABSTRACT To explore the functions of Txnip and its mechanism in adipocyte differentiation, the preadipocytes were isolated from subcutaneous adipose tissue of three-day-old piglets and induced into adipogenic differentiation. The expression of Txnip and ChREBP was silenced, and the Txnip overexpression was achieved in the cells with transfection of the recombinant lentivirus strategies. Txnip silencing promoted the differentiation of porcine preadipocytes and PPARγ expression, and a PPARγ inhibitor reduced this facilitation. Instead, Txnip overexpression exerted a suppressive effect on the cell differentiation and PPARγ expression, and the PPARγ agonist offset this inhibition. High glucose stimulated the preadipocyte differentiation and expressions of ChREBP and Txnip. In contrast, Txnip expression was reduced by ChREBP silencing, suggesting glucose-regulated Txnip expression through the mediation of ChREBP. Moreover, the expressions of ChREBP and Glut4 induced by high glucose and glucose uptake of the cells were reduced by Txnip-overexpression, but increased by Txnip silencing, while these changes of Txnip did not alter their expressions under low glucose. Collectively, Txnip could be an inhibitor of porcine preadipocyte differentiation, which attenuated the adipogenesis through the negative feedback regulation on PPARγ. Txnip impaired the induction of glucose on the preadipocyte differentiation through decreasing Glut4 expression and glucose uptake and subsequent decrease of the expression and transcriptional activity of ChREBP.

Abstract Background Pneumoconiosis is the most prevalent occupational disease and displays different patterns in each province of China. Clarifying specific incidence patterns and temporal trends in Zhejiang Province can help provide valuable information on the prevention of pneumoconiosis. Methods Annual reports of pneumoconiosis for Zhejiang Province from 2006 to 2020 were extracted from the National Occupational Disease and Occupational Health Information Monitoring System. The information of cases included regions, diagnosis ages, genders, exposure durations, pneumoconiosis categories and stages, the first year of exposure, enterprise industries, scales and ownerships. Results Totally 6037 new cases of pneumoconiosis were reported between 2006 and 2020, which increased at first and then gradually declined since 2013. Among all pneumoconiosis cases, silicosis accounted for the majority (72.17%). Most of the cases occurred in small-scale and domestic-funded enterprises, which accounted for 71.75% and 96.97%, respectively. When analyzing the industry distribution, the cases were mainly concentrated in mining (37.12%), manufacturing (31.11%) and ‘public administration and social organization’ (23.94%) industry. The average diagnosis age among the pneumoconiosis cases was 55.44 years, and the median exposure duration was 11.00 years. Significantly older diagnosis age and longer exposure duration were found in females, coal workers’ pneumoconiosis cases, cases with higher stages, cases with the first year of dust exposure earlier and cases from large-scale companies. In regional distribution, the top three cities reporting the most pneumoconiosis cases in Zhejiang Province were Taizhou, Quzhou and Hangzhou. Conclusion The current situation of pneumoconiosis in Zhejiang Province was still serious, and government should further strengthen the surveillance of occupational diseases and supervision of enterprises. Moreover, publicity and education regarding pneumoconiosis should be carried out to raise awareness of dust exposure risk and associated health consequences.

The hydration characteristics, performance, and economic feasibility of inorganic cementitious materials prepared using circulating fluidized bed fly ash (FA), carbide slag (CS), and flue-gas-desulfurization gypsum (FGDG) are investigated, focusing particularly on FA-CS binary and FA-CS-FGDG ternary cementitious systems. Experimental results show that the compressive strength of the binary system is less than that of the ternary one. The ternary cementitious material exhibits strong synergistic effects, as the 28 days compressive strength of the ternary system can reach 6.35 MPa, suggesting that it has good prospects for practical application. A dry-mixed mortar using the material has been manufactured and tested in a pilot project; it meets Chinese government quality standards and reduces cost and carbon emissions relative to traditional mortar. The 28 days compressive strength of dry mix mortar can reach 13.1 MPa, the production cost of solid waste-based dry-mixed mortar was reduced by approximately 48.8%, and the carbon dioxide emission reduction ratio was 82.9%.

Abstract Background Numerous studies have shown that gluten aggregation properties directly affect the processing quality of wheat, however, the genetic basis of gluten aggregation properties were rarely reported. Results To explore the genetic basis of gluten aggregation properties in wheat, an association population consisted with 207 wheat genotypes were constructed for evaluating nine parameters of aggregation properties on GlutoPeak across three-year planting seasons. A total of 940 significant SNPs were detected for 9 GlutoPeak parameters through genome-wide association analysis (GWAS). Finally, these SNPs were integrated to 68 non-redundant QTL distributed on 20 chromosomes and 54 QTL was assigned as pleiotropic loci which accounting for multiple parameters of gluten aggregation property. Furthermore, the peak SNPs representing 54 QTL domonstrated additive effect on all the traits. There was a significant positive correlation between the number of favorable alleles and the phenotypic values of each parameter. Peak SNPs of two novel QTL, q3AL.2 and q4DL, which contributing to both PMT (peak maximum time) and A3 (area from the first minimum to torque 15 s before the maximum torque) parameters, were selected for KASP (Kompetitive Allele Specific PCR) markers development and the KASP markers can be used for effectively evaluating the quality of gluten aggregation properties in the association population. Conclusion The rapid and efficient GlutoPeak method for gluten measurement can be used for early selection of wheat breeding. This study revealed the genetic loci related to GlutoPeak parameters in association population, which would be helpful to develop wheat elite lines with improved gluten aggregation through molecular marker-assisted breeding.

Circular RNA (circRNA) has been confirmed to be the key regulators of diabetic nephropathy (DN) progression. However, the role of circ_0114428 in the DN progression remains unclear. Glomerular mesangial cells (GMCs) were treated with high glucose (HG) to mimic DN cell models in vitro. The expression levels of circ_0114428, microRNA (miR)-185-5p, and SMAD3 mRNA were examined by quantitative real-time PCR. Cell proliferation ability was detected by MTT assay, EdU staining and flow cytometry. The protein levels of proliferation marker, fibrosis markers, epithelial-mesenchymal transition (EMT) markers and SMAD3 were measured by western blot assay. The interaction between miR-185-5p and circ_0114428 or SMAD3 was confirmed via dual-luciferase reporter assay, RIP assay and RNA pull-down assay. Our data showed that circ_0114428 was upregulated in HG-induced GMCs. Circ_0114428 overexpression could aggravate the promotion effect of HG on the proliferation, fibrosis and EMT process of GMCs, while its knockdown had an opposite effect. In the terms of mechanisms, circ_0114428 could sponge miR-185-5p to regulate SMAD3. MiR-185-5p inhibitor could reverse the suppressive effect of circ_0114428 knockdown on the proliferation, fibrosis and EMT process in HG-induced GMCs. Also, SMAD3 overexpression abolished the inhibition of miR-185-5p on the proliferation, fibrosis and EMT process in HG-induced GMCs. Taken together, our data suggested that circ_0114428 might promote DN progression by regulating the miR-185-5p/SMAD3 axis.

Background Immunotherapy, including adoptive cell therapy (ACT) and immune checkpoint inhibitors (ICIs), has a limited effect in most patients with colorectal cancer (CRC), and the efficacy is further limited in patients with liver metastasis. Lack of antitumor lymphocyte infiltration could be a major cause, and there remains an urgent need for more potent and safer therapies for CRC.Methods In this study, the antitumoral synergism of low molecular weight heparin (LMWH) combined with immunotherapy in the microsatellite stable (MSS) highly aggressive murine model of CRC was fully evaluated.Results Dual LMWH and ACT objectively mediated the stagnation of tumor growth and inhibition of liver metastasis, neither LMWH nor ACT alone had any antitumoral activity on them. The combination of LMWH and ACT obviously increased the infiltration of intratumor CD8+ T cells, as revealed by multiplex immunohistochemistry, purified CD8+ T-cell transfer assay, and IVIM in vivo imaging. Mechanistically, evaluation of changes in the tumor microenvironment revealed that LMWH improved tumor vascular normalization and facilitated the trafficking of activated CD8+ T cells into tumors. Similarly, LMWH combined with anti-programmed cell death protein 1 (PD-1) therapy provided superior antitumor activity as compared with the single PD-1 blockade in murine CT26 tumor models.Conclusions LMWH could enhance ACT and ICIs-based immunotherapy by increasing lymphocyte infiltration into tumors, especially cytotoxic CD8+ T cells. These results indicate that combining LMWH with an immunotherapy strategy presents a promising and safe approach for CRC treatment, especially in MSS tumors.