Environmental and occupational exposure to cadmium associated with male reproductive health risk: a systematic review and meta-analysis based on epidemiological evidence.

There is an abundance of epidemiological evidence and animal experiments concerning the correlation between cadmium exposure and adverse male reproductive health outcomes. However, the evidence remains inconclusive. We conducted a literature search from PubMed, Embase, and Web of Science over the past 3 decades. Pooled r and 95% confidence intervals (CIs) were derived from Cd levels of the type of biological materials and different outcome indicators to address the large heterogeneity of existing literature. Cd was negatively correlated with semen parameters (r = - 0.122, 95% CI - 0.151 to - 0.092) and positively correlated with sera sex hormones (r = 0.104, 95% CI 0.060 to 0.147). Among them, Cd in three different biological materials (blood, semen, and urine) was negatively correlated with semen parameters, while among sex hormones, only blood and urine were statistically positively correlated. In subgroup analysis, blood Cd was negatively correlated with semen density, sperm motility, sperm morphology, and sperm count. Semen Cd was negatively correlated with semen concentration. As for serum sex hormones, blood Cd had no statistical significance with three hormones, while semen Cd was negatively correlated with testosterone. In summary, cadmium exposure might be associated with the risk of a decline in sperm quality and abnormal levels of sex hormones.

Triggering High Capacity and Superior Reversibility of Manganese Oxides Cathode via Magnesium Modulation for Zn//MnO2 Batteries.

Aqueous zinc-ion batteries (ZIBs) have attracted extensive attention in recent years because of its high volumetric energy density, the abundance of zinc resources, and safety. However, ZIBs still suffer from poor reversibility and sluggish kinetics derived from the unstable cathodic structure and the strong electrostatic interactions between bivalent Zn2+ and cathodes. Herein, magnesium doping into layered manganese dioxide (Mg-MnO2 ) via a simple hydrothermal method as cathode materials for ZIBs is proposed. The interconnected nanoflakes of Mg-MnO2 possess a larger specific surface area compared to pristine δ-MnO2 , providing more electroactive sites and boosting the capacity of batteries. The ion diffusion coefficients of Mg-MnO2 can be enhanced due to the improved electrical conductivity by doped cations and oxygen vacancies in MnO2 lattices. The assembled Zn//Mg-MnO2 battery delivers a high specific capacity of 370 mAh g-1 at a current density of 0.6 A g-1 . Furthermore, the reaction mechanism confirms that Zn2+ insertion occurred after a few cycles of activation reactions. Most important, the reversible redox reaction between Zn2+ and MnOOH is found after several charge-discharge processes, promoting capacity and stability. It believes that this systematic research enlightens the design of high-performance of ZIBs and facilitates the practical application of Zn//MnO2 batteries.

The apoptotic effects of soybean agglutinin were induced through three different signal pathways by down-regulating cytoskeleton proteins in IPEC-J2 cells.

Soybean agglutinin (SBA) is a main anti-nutritional factor in soybean. SBA exhibits its anti-nutritional functions by binding to intestinal epithelial cells. Keratin8 (KRT8), Keratin18 (KRT18) and Actin (ACTA) are the representative SBA-specific binding proteins. Such cytoskeletal proteins act a crucial role in different cell activities. However, limited reports reveal what the signal transduction pathway of apoptosis caused by SBA when binding to KRT8, KRT18 and ACTA. We aimed to evaluate the effects of SBA on cell apoptosis and the expression of the cytoskeletal protein (KRT8, KRT18 and ACTA), reveal the roles of these cytoskeletal proteins or their combinations on SBA-induced cell apoptosis in IPEC-J2 cell line, evaluate the influences of SBA on the mitochondria, endoplasmic reticulum stress and death receptor-mediated apoptosis signal pathway and to show the roles of KRT8, KRT18 and ACTA in different apoptosis signal pathways induced by SBA. The results showed that SBA induced the IPEC-J2 cell apoptosis and decreased the mRNA expression of KRT8, KRT18 and ACTA (p < 0.05). The degree of effect of three cytoskeleton proteins on cell apoptosis was ACTA > KRT8 > KRT18. The roles of these three cytoskeletal proteins on IPEC-J2 apoptotic rates had a certain accumulation effect. SBA up-regulated mitochondrial fission variant protein (FIS1) and fusion protein (Mfn2) promoted CytC and AIF in mitochondria to enter the cytoplasm, activated caspase-9 and caspase-3, damaged or declined mitochondrial function and reduced ATP synthesis (p < 0.05). Also, SBA up-regulated the expression of GRP78, XBP-1, eIF2α, p-eIF2α and CHOP (p < 0.05), down-regulated the expression level of ASK1 protein (p < 0.05). SBA led to the recruitment of FADD to the cytoplasmic membrane and increased the expression of FasL, resulting in caspase-8 processing. SBA up-regulated the expression level of Bax protein and decreased cytosolic Bcl-2 and Bid (p < 0.05). In addition, there was a significant negative correlation between the gene expression of cytoskeleton proteins and apoptosis, as well as the expression of key proteins of apoptosis-related signal transduction pathways. In conclusion, SBA induced the activation of the mitochondria, endoplasmic reticulum stress and the death receptor-mediated apoptosis signal pathway and the crosstalk between them. The effect of SBA on these three pathways was mainly exhibited via down-regulation of the mRNA expression of the three cytoskeletal expressions. This study elucidates the molecular mechanism and signaling pathway of SBA that lead to apoptosis from the perspective of cell biology and molecular biology and provides a new perspective on the toxicity mechanism of other food-derived anti-nutrients, medical gastrointestinal health and related cancer treatment.

MicroRNA-9 restrains the sharp increase and boost apoptosis of human acute myeloid leukemia cells by adjusting the Hippo/YAP signaling pathway.

MicroRNAs (miRNAs) play a very important role in the development of acute myeloid leukemia (AML). This study focuses on the effects of miR-9 on the regulation of AML cells and their related signaling pathways. We found that the expression of miR-9 was significantly decreased in four AML cell lines (THP-1, HL-60, TF-1 and KG-1) compared with the human normal bone marrow cells (HS-5). Moreover, miR-9 overexpression inhibited HL-60 cell proliferation ability, and promoted apoptosis. However, interfering with miR-9 expression promoted the proliferation of HL-6 cells and inhibited apoptosis. Western blotting results subsequently showed that overexpression of miR-9 could elevate the expression of MAT1, LATS1, and LATS2 in HL-60 cells, and inhibit the expression of YAP, while the interference with miR-9 had the opposite result. Taken together, miR-9 may act as a tumor suppressor by activating the Hippo/YAP signaling pathway of AML cells, which in this way supply ideas for the clinical remedy of AML patients.

Possible aerosol transmission of COVID-19 and special precautions in dentistry.

Since its emergence in December 2019, corona virus disease 2019 (COVID-19) has impacted several countries, affecting more than 90 thousand patients and making it a global public threat. The routes of transmission are direct contact, and droplet and possible aerosol transmissions. Due to the unique nature of dentistry, most dental procedures generate significant amounts of droplets and aerosols, posing potential risks of infection transmission. Understanding the significance of aerosol transmission and its implications in dentistry can facilitate the identification and correction of negligence in daily dental practice. In addition to the standard precautions, some special precautions that should be implemented during an outbreak have been raised in this review.

Autotransplantation of third molars with completely formed roots to replace compromised molars with the computer-aided rapid prototyping.

OBJECTIVE: To describe a method to fabricate donor tooth replica to assist surgeons in preparation of recipient socket during tooth autotransplantation. MATERIALS AND METHODS: A total of 28 compromised molars in 27 patients were transplanted with third molars using computer-aided rapid prototyping (CARP) technique. Surgery time and extra-alveolar time were documented. Postoperatively, the distance between cervix of transplanted tooth and the alveolar wall was measured. The degree of postoperative pain experienced was assessed with visual analog scale at day 1, 3, and 7. RESULTS: From 28 clinical cases, the average extra-alveolar time and surgery time were 2.5 minutes (±1.3) and 44 minutes (±6.8), respectively. Postoperatively, the average distance between cervix of transplanted tooth and the alveolar wall was 0.87 mm (±0.15) at the mesial-cervix, 0.95 mm (±0.17) at the distal-cervix, 0.88 mm (±0.18) at the buccal-cervix, and 0.95 mm (±0.13) at the lingual-cervix. The value of visual analog scale score significantly decreased from day 1 to day 3. CONCLUSIONS: CARP is a reliable technique for fabrication of tooth like surgical replicas in conventional autotransplantation. CLINICAL SIGNIFICANCE: CARP technique minimized extra-oral time, reduced iatrogenic damage, and consequently increased the survival rate of tooth autotransplantation.

miR-153 suppresses IDO1 expression and enhances CAR T cell immunotherapy.

BACKGROUND: Indoleamine 2,3-dioxygenase 1 (IDO1) catalyzes the first and rate-limiting step in converting tryptophan to kynurenine. Chimeric antigen receptor (CAR) T cells are T cells with recombinant receptors targeting tumor-associated antigens. The Food and Drug Administration has approved CAR T cells that target CD19 for treatment of advanced B cell leukemia and lymphoma. However, CAR T cell therapy in solid tumors has been hampered by multiple obstacles. Preclinical and clinical studies suggest that combinatorial immune checkpoint blockade and IDO1 inhibition provide durable therapeutic efficacy against cancer. Yet, the combination of IDO1 inhibition and CAR T has not been attempted. METHODS: We analyze IDO1 downregulation by miR-153 in colon cancer cells and the association of IDO1 and miR-153 expression with colorectal patient survival. We generate CAR T cells targeting the epidermal growth factor receptor variant III and measure their tumor killing effects against colon cancer cells with or without miR-153 overexpression by killing assays and in xenografts. RESULTS: IDO1 is highly expressed in colorectal tumors and is inversely associated with patient survival. miR-153 directly inhibits IDO1 expression by targeting its 3' untranslated region in colon cancer cells; yet, miR-153 overexpression does not affect cancer cell survival, apoptosis, and colony formation. When colon cancer cells are targeted by CAR T cells, miR-153 overexpression within tumor cells significantly enhances T cell killing in vitro and suppresses xenograft tumor growth in mice. CONCLUSIONS: These findings indicate that miR-153 inhibits IDO1 expression in colon cancer cells and is a tumor-suppressive miRNA that enhances CAR T cell immunotherapy. This study supports the combinatorial use of IDO1 inhibitors and CAR T cells in treating solid tumors.

DKK1 rescues osteogenic differentiation of mesenchymal stem cells isolated from periodontal ligaments of patients with diabetes mellitus induced periodontitis.

Multiple studies have shown that diabetes mellitus is an established risk factor for periodontitis. Recently mesenchymal stem cells derived from periodontal ligament (PDLSCs) have been utilized to reconstruct tissues destroyed by chronic inflammation. However, impact of periodontitis with diabetes mellitus on PDLSCs and mechanisms mediating effects of complex microenvironments remain poorly understood. In this study, we found multiple differentiation potential of PDLSCs from chronic periodontitis with diabetes mellitus donors (D-PDLSCs) was damaged significantly. Inhibition of NF-κB signaling could rescue osteogenic potential of PDLSCs from simple chronic periodontitis patients (P-PDLSCs), whereas did not promote D-PDLSCs osteogenesis. In addition, we found expression of DKK1 in D-PDLSCs did not respond to osteogenic signal and decreased osteogenic potential of D-PDLSCs treated with DKK1 could be reversed. To further elucidate different character between P-PDLSCs and D-PDLSCs, we treated PDLSCs with TNF-α and advanced glycation end products (AGEs), and find out AGEs which enhance effect of TNF-α in PDLSCs might mediate special personality of D-PDLSCs. The adverse effect of AGEs in PDLSCs could be reversed when PDLSCs were treated with DKK1. These results suggested DKK1 mediating WNT signaling might be a therapy target to rescue potential of PDLSCs in periodontitis with diabetes mellitus.

Correlation of increased plasma osteoprotegerin and cardiovascular risk factors in patients with adult growth hormone deficiency.

Adult growth hormone deficiency (AGHD) is correlated to many adverse effects on metabolism and increases cardiovascular risk. 40 patients with AGHD and 40 healthy subjects were included. Anthropometric parameters such as body mass index, waist circumference, and waist-hip ratio were measured. Meanwhile, plasma levels of total cholesterol, triglyceride, high sensitivity C-relative protein, interleukin-6 and OPG were determined. Homeostasis model assessments for insulin resistance (HOMA-IR) and ß-cell function (HOMA-ß) were calculated using homeostasis model. Plasma OPG concentrations of AGHD patients were significantly higher than those in healthy subjects (131.82 ± 45.04 versus 81.02 ± 45.04, P < 0.01). Plasma OPG levels were positively correlated with age, body mass index, waist circumference, hip circumference, waist-hip ratio, fasting insulin, total cholesterol, triglyceride, high sensitivity C-relative protein and interleukin-6 (P < 0.05), but negatively correlated with high-density lipoprotein cholesterol (P < 0.05). Multiple linear stepwise regression analysis demonstrated that body mass index, triglyceride, and interleukin-6 were independently related to plasma OPG levels (P < 0.05). The levels of plasma OPG were increased in AGHD patients and were closely correlated with glycolipid metabolism and chronic inflammation. OPG might play an important role in the occurrence and development of cardiovascular diseases in AGHD patients.

A time-critical adaptive approach for visualizing natural scenes on different devices.

To automatically adapt to various hardware and software environments on different devices, this paper presents a time-critical adaptive approach for visualizing natural scenes. In this method, a simplified expression of a tree model is used for different devices. The best rendering scheme is intelligently selected to generate a particular scene by estimating the rendering time of trees based on their visual importance. Therefore, this approach can ensure the reality of natural scenes while maintaining a constant frame rate for their interactive display. To verify its effectiveness and flexibility, this method is applied in different devices, such as a desktop computer, laptop, iPad and smart phone. Applications show that the method proposed in this paper can not only adapt to devices with different computing abilities and system resources very well but can also achieve rather good visual realism and a constant frame rate for natural scenes.

[Effect of lipopolysaccharide on proliferation and inflammatory factors expression of human periodontal ligament stem cells].

OBJECTIVE: To investigate the effect of Porphyromonas gingivalis lipopolysaccharide (LPS) on proliferation and inflammatory factors expression of human periodontal ligament stem cells (HPDLSCs). METHODS: HPDLSCs were cultivated and identified. Experiment was divided into 3 groups according to culture solution: Group A with alpha-MEM culture solution containing 10 microg.mL-1 LPS, group B with supernatant fluid containing 10ng.mL-1 LPS stimulated monocyte, group C with alpha-MEM culture solution. The proliferation ability of HPDLSCs was analyzed by MTF assay. The expression levels of interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor (TNF-alpha) mRNA of HPDLSCs were detected by reverse transcriptase polymerase chain reaction(RT-PCR). RESULTS: HPDLSCs had clonality, bone and fat differentiation ability. Compared with group C, the proliferation ability of HPDLSCs of group A and group B was significantly inhibited, and the proliferation ability of HPDLSCs of group B were more significantly inhibited than that of group A (P<0.05). The expression of IL-1beta, IL-6 and TNF-alpha mRNA of group A and group B increased compared with the control group, and the expression of IL-1beta, IL-6 and TNF-alpha mRNA of group B increased more than that of group A (P<0.05). CONCLUSION: Porphyromonas gingivalis may inhibit the proliferation of HPDLSCs directly or indirectly through LPS and increase expression of inflammatory factor, exacerbate periodontal inflammatory tissue damage and delay the self-repairing of periodontal tissue.

Activation of type I and III interferon signalling pathways occurs in lung epithelial cells infected with low pathogenic avian influenza viruses.

The host response to the low pathogenic avian influenza (LPAI) H5N2, H5N3 and H9N2 viruses were examined in A549, MDCK, and CEF cells using a systems-based approach. The H5N2 and H5N3 viruses replicated efficiently in A549 and MDCK cells, while the H9N2 virus replicated least efficiently in these cell types. However, all LPAI viruses exhibited similar and higher replication efficiencies in CEF cells. A comparison of the host responses of these viruses and the H1N1/WSN virus and low passage pH1N1 clinical isolates was performed in A549 cells. The H9N2 and H5N2 virus subtypes exhibited a robust induction of Type I and Type III interferon (IFN) expression, sustained STAT1 activation from between 3 and 6 hpi, which correlated with large increases in IFN-stimulated gene (ISG) expression by 10 hpi. In contrast, cells infected with the pH1N1 or H1N1/WSN virus showed only small increases in Type III IFN signalling, low levels of ISG expression, and down-regulated expression of the IFN type I receptor. JNK activation and increased expression of the pro-apoptotic XAF1 protein was observed in A549 cells infected with all viruses except the H1N1/WSN virus, while MAPK p38 activation was only observed in cells infected with the pH1N1 and the H5 virus subtypes. No IFN expression and low ISG expression levels were generally observed in CEF cells infected with either AIV, while increased IFN and ISG expression was observed in response to the H1N1/WSN infection. These data suggest differences in the replication characteristics and antivirus signalling responses both among the different LPAI viruses, and between these viruses and the H1N1 viruses examined. These virus-specific differences in host cell signalling highlight the importance of examining the host response to avian influenza viruses that have not been extensively adapted to mammalian tissue culture.