Liver ChREBP deficiency inhibits fructose-induced insulin resistance in pregnant mice and female offspring.

High fructose intake during pregnancy increases insulin resistance (IR) and gestational diabetes mellitus (GDM) risk. IR during pregnancy primarily results from elevated hormone levels. We aim to determine the role of liver carbohydrate response element binding protein (ChREBP) in insulin sensitivity and lipid metabolism in pregnant mice and their offspring. Pregnant C57BL/6J wild-type mice and hepatocyte-specific ChREBP-deficient mice were fed with a high-fructose diet (HFrD) or normal chow diet (NC) pre-delivery. We found that the combination of HFrD with pregnancy excessively activates hepatic ChREBP, stimulating progesterone synthesis by increasing MTTP expression, which exacerbates IR. Increased progesterone levels upregulated hepatic ChREBP via the progesterone-PPARγ axis. Placental progesterone activated the progesterone-ChREBP loop in female offspring, contributing to IR and lipid accumulation. In normal dietary conditions, hepatic ChREBP modestly affected progesterone production and influenced IR during pregnancy. Our findings reveal the role of hepatic ChREBP in regulating insulin sensitivity and lipid homeostasis in both pregnant mice consuming an HFrD and female offspring, and suggest it as a potential target for managing gestational metabolic disorders, including GDM.

Moscatilin inhibits vascular calcification by activating IL13RA2-dependent inhibition of STAT3 and attenuating the WNT3/ß-catenin signalling pathway.

INTRODUCTION: Vascular calcification, a devastating vascular complication accompanying atherosclerotic cardiovascular disease and chronic kidney disease, increases the incidence of adverse cardiovascular events and compromises the efficacy of vascular interventions. However, effective therapeutic drugs and treatments to delay or prevent vascular calcification are lacking. OBJECTIVES: This study was designed to test the therapeutic effects and mechanism of Moscatilin (also known as dendrophenol) from Dendrobium huoshanense (an eminent traditional Chinese medicine) in suppressing vascular calcification in vitro, ex vivo and in vivo. METHODS: Male C57BL/6J mice (25-week-old) were subjected to nicotine and vitamin D3 (VD3) treatment to induce vascular calcification. In vitro, we established the cellular model of osteogenesis of human aortic smooth muscle cells (HASMCs) under phosphate conditions. RESULTS: By utilizing an in-house drug screening strategy, we identified Moscatilin as a new naturally-occurring chemical entity to reduce HASMC calcium accumulation. The protective effects of Moscatilin against vascular calcification were verified in cultured HASMCs. Unbiased transcriptional profiling analysis and cellular thermal shift assay suggested that Moscatilin suppresses vascular calcification via binding to interleukin 13 receptor subunit A2 (IL13RA2) and augmenting its expression. Furthermore, IL13RA2 was reduced during HASMC osteogenesis, thus promoting the secretion of inflammatory factors via STAT3. We further validated the participation of Moscatilin-inhibited vascular calcification by the classical WNT/ß-catenin pathway, among which WNT3 played a key role in this process. Moscatilin mitigated the crosstalk between WNT3/ß-catenin and IL13RA2/STAT3 to reduce osteogenic differentiation of HASMCs. CONCLUSION: This study supports the potential of Moscatilin as a new naturally-occurring candidate drug for treating vascular calcification via regulating the IL13RA2/STAT3 and WNT3/ß-catenin signalling pathways.

Ni Single-Atoms Based Memristors with Ultrafast Speed and Ultralong Data Retention.

Memristor with low-power, high density, and scalability fulfills the requirements of the applications of the new computing system beyond Moore's law. However, there are still nonideal device characteristics observed in the memristor to be solved. The important observation is that retention and speed are correlated parameters of memristor with trade off against each other. The delicately modulating distribution and trapping level of defects in electron migration-based memristor is expected to provide a compromise method to address the contradictory issue of improving both switching speed and retention capability. Here, high-performance memristor based on the structure of ITO/Ni single-atoms (NiSAs/N-C)/Polyvinyl pyrrolidone (PVP)/Au is reported. By utilizing well-distributed trapping sites , small tunneling barriers/distance and high charging energy, the memristor with an ultrafast switching speed of 100 ns, ultralong retention capability of 106  s, a low set voltage (Vset ) of ≈0.7 V, a substantial ON/OFF ration of 103 , and low spatial variation in cycle-to-cycle (500 cycles) and device-to-device characteristics (128 devices) is demonstrated. On the premise of preserving the strengths of a fast switching speed, this memristor exhibits ultralong retention capability comparable to the commercialized flash memory. Finally, a memristor ratioed logic-based combinational memristor array to realize the one-bit full adder is further implemented.

Microstructure, Mechanical Properties and Fatigue Crack Growth Behavior of Gas Tungsten Arc Welding Welded Joint of the Hastelloy N Alloy.

Hastelloy N alloy is an excellent oxidation and corrosion-resistant material, which is selected as the shell material for the main vessel of molten salt reactors (MSRs). In this work, we conducted double-sided gas tungsten arc welding (GTAW) on 4 mm thick Hastelloy N alloy plates to examine the microstructure and mechanical properties of the welded joints. The S-N curve was obtained by fatigue test. The experimental results show that fatigue cracks initiate along the weld toe and propagate inward in a fan-shaped pattern. The hardness is highest in the heat-affected zone (HAZ). The fracture mode observed was trans-granular. The plastic zone in the initial stages of crack propagation remained relatively minimal. However, it gradually expanded during subsequent stages of the process. It is noteworthy that the crack propagation process often involves the development of secondary cracks, accompanied by profound plasticity-induced closure effects. The results of our investigation demonstrate that the welded joint exhibits excellent fatigue performance.

N-glycosylation by N-acetylglucosaminyltransferase IVa enhances the interaction of integrin ß1 with vimentin and promotes hepatocellular carcinoma cell motility.

N-glycosylation has been revealed to be tightly associated with cancer metastasis. As a key transferase that catalyzes the formation of ß1,4 N-acetylglucosamine (ß1,4GlcNAc) branches on the mannose core of N-glycans, N-acetylglucosaminyltransferase IVa (GnT-IVa) has been reported to be involved in hepatocellular carcinoma (HCC) metastasis by forming N-glycans; however, the underlying mechanisms are largely unknown. In the current study, we found that GnT-IVa was upregulated in HCC tissues and positively correlated with worse outcomes in HCC patients. We found that GnT-IVa could promote tumor growth in mice; notably, this effect was attenuated after mutating the enzymatic site (D445A) of GnT-IVa, suggesting that GnT-IVa regulated HCC progression by forming ß1,4GlcNAc branches. To mechanistically investigate the role of GnT-IVa in HCC, we conducted GSEA and GO functional analysis as well as in vitro experiments. The results showed that GnT-IVa could enhance HCC cell migration, invasion and adhesion ability and increase ß1,4GlcNAc branch glycans on integrin ß1 (ITGB1), a tumor-associated glycoprotein that is closely involved in cell motility by interacting with vimentin. Interruption of ß1,4GlcNAc branch glycan modification on ITGB1 could suppress the interaction of ITGB1 with vimentin and inhibit cell motility. These results revealed that GnT-IVa could promote HCC cell motility by affecting the biological functions of ITGB1 through N-glycosylation. In summary, our results revealed that GnT-IVa is highly expressed in HCC and can form ß1,4GlcNAc branches on ITGB1, which are essential for interactions with vimentin to promote HCC cell motility. These findings not only proposed a novel mechanism for GnT-IVa in HCC progression but also revealed the significance of N-glycosylation on ITGB1 during the process, which may provide a novel target for future HCC therapy.

Optimizing enteral nutrition delivery by implementing volume-based feeding protocol for critically ill patients: an updated meta-analysis and systematic review.

BACKGROUND: This study aims to provide an updated assessment of the efficacy of optimized enteral nutrition (EN) delivery by implementing the volume-based feeding (VBF) protocol in critically ill patients. METHODS: We updated our previous literature retrieval with no language restrictions. The inclusion criteria were:1) Participants: Critically ill patients (Patients who was admitted in ICU; 2) Intervention: The VBF protocol was adopted for EN administration; 3) Comparison: The rate-based feeding (RBF) protocol was adopted for EN administration; 4) Major outcomes: EN nutrition delivery. The exclusion criteria included participants aged < 18 years, duplicated literature, animal and cellular experiments, and studies lacking any of the outcomes mentioned in the inclusion criteria. The databases included MEDLINE (through PubMed), Web of Science, Cochrane Library, Chinese Biomedical Literature Service System (SinoMed), Wanfang Data Knowledge Service Platform, and China National Knowledge Infrastructure. RESULT: Sixteen studies involving a total of 2896 critically ill patients are included in the updated meta-analysis. Compared with the previous meta-analysis, nine new studies were added that included 2205 more patients. The VBF protocol significantly improved energy (MD = 15.41%, 95% CI: [10.68, 20.14], p < 0.00001) and protein (MD = 22.05%, 95% CI: [10.89, 33.22], p = 0.0001) delivery. The patients in the VBF group stayed in the ICU for a shorter time (MD = 0.78, 95% CI: [0.01, 1.56], p = 0.05). The VBF protocol did not increase the risk of death (RR = 1.03, 95% CI: [0.85, 1.24], p = 0.76) or prolong the mechanical ventilation duration (MD = 0.81, 95% CI: [-0.30,1.92], p = 0.15). In addition, the VBF protocol did not affect EN complications, such as diarrhea (RR = 0.91, 95% CI: [0.73, 1.15], p = 0.43), emesis (RR = 1.23, 95% CI: [0.76, 1.99], p = 0.41), feeding intolerance (RR = 1.14, 95% CI: [0.63, 2.09], p = 0.66), and gastric retention (RR = 0.45, 95% CI: [0.16, 1.30], p = 0.14). CONCLUSION: Our study revealed that the VBF protocol significantly improved calorie and protein delivery in critically ill patients with no additional risk.

Nogo-B inhibition restricts ulcerative colitis via inhibiting p68/miR-155 signaling pathway.

BACKGROUND & AIMS: Ulcerative colitis (UC) is a main type of inflammatory bowel diseases which spreads globally during the westernization of lifestyle over the past few decades. However, the cause of UC is still not fully understood. We aimed to disclose the role of Nogo-B in the development of UC. METHODS: Nogo-deficiency (Nogo-/-) and wild-type male mice were treated with dextran sodium sulfate (DSS) to conduct a UC model, followed by determination of colon and serum inflammatory cytokines level. RAW264.7, THP1 and NCM460 cells were used to determine macrophage inflammation as well as proliferation and migration of NCM460 cells under Nogo-B or miR-155 intervention. RESULTS: Nogo deficiency significantly reduced DSS-induced weight loss, colon length and weight reduction, and inflammatory cells accumulation in the intestinal villus, while increased the expression of tight junctions (TJs) proteins (Zonula occludens-1, Occludin) and adherent junctions (AJs) proteins (E-cadherin, α-catenin), implying that Nogo deficiency attenuated DSS-induced UC. Mechanistically, Nogo-B deficiency reduced TNFα, IL-1ß and IL-6 levels in the colon, serum, RAW264.7 cells and THP1-derived macrophages. Furthermore, we identified that Nogo-B inhibition can reduce the maturation of miR-155, which is essential for Nogo-B-affected inflammatory cytokines expression. Interestingly, we determined that Nogo-B and p68 can interact with each other to promote the expression and activation of Nogo-B and p68, thus facilitating miR-155 maturation to induce macrophage inflammation. Blocking p68 inhibited Nogo-B, miR-155, TNFα, IL-1ß and IL-6 expression. Moreover, the culture medium collected from Nogo-B overexpressed macrophages can inhibit enterocytes NCM460 cells proliferation and migration. CONCLUSION: We disclose that Nogo deficiency reduced DSS-induced UC via inhibiting p68-miR-155-activated inflammation. Our results indicate that Nogo-B inhibition serves as a new potential therapeutic candidate for the prevention and treatment of UC.

Overexpression of NgBR inhibits high-fat diet-induced atherosclerosis in ApoE-deficiency mice.

BACKGROUND: Hyperlipidemia (hypercholesterolemia and/or hypertriglyceridemia) is a risk factor for atherosclerosis. Nogo-B receptor (NgBR) plays important roles in hepatic steatosis and cholesterol transport. However, the effect of NgBR overexpression on atherosclerosis remains unknown. MATERIALS AND METHODS: Apolipoprotein E deficient (ApoE-/-) mice infected with adeno-associated virus (AAV)-NgBR expression vector were fed a high-fat diet for 12 weeks, followed by determination of atherosclerosis and the involved mechanisms. RESULTS: We determined that high expression of NgBR by AAV injection mainly occurs in the liver and it can substantially inhibit en face and aortic root sinus lesions. NgBR overexpression also reduced levels of inflammatory factors in the aortic root and serum, and levels of cholesterol, triglyceride, and free fatty acids in the liver and serum. Mechanistically, NgBR overexpression increased the expression of scavenger receptor type BI and the genes for bile acid synthesis, and decreased the expression of cholesterol synthesis genes by reducing sterol regulatory element-binding protein 2 maturation in the liver, thereby reducing hypercholesterolemia. In addition, NgBR overexpression activated AMP-activated protein kinase α via the Ca2+ signaling pathway, which inhibited fat synthesis and improved hypertriglyceridemia. CONCLUSIONS: Taken together, our study demonstrates that overexpression of NgBR enhanced cholesterol metabolism and inhibited cholesterol/fatty acid synthesis to reduce hyperlipidemia, and reduced vascular inflammation, thereby inhibiting atherosclerosis in ApoE-/- mice. Our study indicates that NgBR might be a potential target for atherosclerosis treatment.

Presence and distribution of triazine herbicides and their effects on microbial communities in the Laizhou Bay, Northern China.

This study investigated the distribution of triazine herbicides in the Laizhou Bay, China and found that the total concentrations of triazine herbicides in the seawater and sediments were 111.15-234.85 ng/L and 0.902-4.661 µg/kg, respectively. Triazine herbicides especially ametryn, atrazine, and simazine were negatively correlated with prokaryote diversity in the seawater. While ametryn, desethylatrazine and desisopropylatrazine had positively significant effects on eukaryotes Dinophyceae, Bacillariophyta, and Cercozoa in the sediments. Moreover, the degree of fragmentation of eukaryotic networks increased dramatically with the increasing numbers of removed nodes, but prokaryotic networks did not change with the decrease of nodes. In addition, the stability analysis and neutral community models revealed that eukaryotes were more sensitive to triazine herbicides than prokaryotes. These results suggest that triazine herbicides might affect the structure and interactions of microbial communities. Therefore, more attentions should be paid to the ecological risk of triazine herbicides in marine ecosystems.

Nanoparticle manipulation using plasmonic optical tweezers based on particle sizes and refractive indices.

As an effective tool for micro/nano-scale particle manipulation, plasmonic optical tweezers can be used to manipulate cells, DNA, and macromolecules. Related research is of great significance to the development of nanoscience. In this work, we investigated a sub-wavelength particle manipulation technique based on plasmonic optical tweezers. When the local plasmonic resonance is excited on the gold nanostructure arrays, the local electromagnetic field will be enhanced to generate a strong gradient force acting on nanoparticles, which could achieve particle sorting in sub-wavelength scale. On this basis, we explored the plasmonic enhancement effect of the sorting device and the corresponding optical force and optical potential well distributions. Additionally, the sorting effect of the sorting device was investigated in statistical methods, which showed that the sorting device could effectively sort particles of different diameters and refractive indices.

Daidzein alleviates doxorubicin-induced heart failure via the SIRT3/FOXO3a signaling pathway.

Heart failure (HF) is a clinical syndrome characterized by typical symptoms that usually occur at the end stage of various heart diseases and lead to death. Daidzein (DAI), an isoflavone found in soy foods, is widely used to treat menopausal syndrome, prostate cancer, breast cancer, heart disease, cardiovascular disease, and osteoporosis, and has anti-oxidant and anti-inflammatory properties. However, the effects of DAI in HF remain unknown. In this study, doxorubicin (DOX) was used to establish HF models of C57BL/6J mice and H9c2 cells with DAI treatment. Our results showed that DAI markedly improved the DOX-induced decline in cardiac function, and decreased the left ventricular ejection fraction, cardiac inflammation, oxidative stress, apoptosis, and fibrosis. Mechanistically, DAI affects cardiac energy metabolism by regulating SIRT3, and meets the ATP demand of the heart by improving glucose, lipid, and ketone body metabolism as well as restoring mitochondrial dysfunction in vivo and in vitro. Additionally, DAI can exert an antioxidant function and alleviate HF through the SIRT3/FOXO3a pathway. In conclusion, we demonstrate that DAI alleviates DOX-induced cardiotoxicity by regulating cardiac energy metabolism as well as reducing inflammation, oxidative stress, apoptosis and fibrosis, indicating its potential application for HF treatment.

Water quality profits by the submerged macrophyte community consisting of multi-functional species-rich groups.

The re-establishment of submerged macrophytes facilitates the formation of a clear-water state in shallow eutrophic lakes. But most restorations of submerged macrophytes are often unstable and cannot maintain a stable clear-water state, probably because the species and functional diversity have not been fully taken into account. In this study, we try to explore submerged macrophyte communities and water quality changes under different submerged macrophyte combinations through mesocosm experiments. We hypothesized that communities with high species and functional diversity would be more conducive to improving water quality. The results showed that the mean community biomass of single-species and 8-species were higher than 5-species. And the stability and mean relative growth rate of the 8-species community were higher than the 5-species community. With the same configuration of three functional groups, the 8-species community was more stable and had better water quality than the 5-species community. The path analysis revealed that different functional groups of submerged macrophytes play different roles. The erect and canopy-producing submerged macrophytes were conducive to reducing total suspended solids (TSS) concentrations in the water column during community construction. In contrast, bottom-dwelling submerged macrophytes were conducive to reducing total nitrogen, total phosphorus, and TSS concentrations during the stage of disturbances. Our results also suggested that canopy-producing groups may have a competitive advantage for light over bottom-dwelling species. Based on the above results and biodiversity insurance hypothesis, we conclude that the community consisting of multi-functional species-rich groups is conducive to building stable submerged macrophyte communities and obtaining a stable clear-water state. Our findings will improve water quality management and pollution control for eutrophic shallow lakes.

Association between fluoroquinolone exposure and children's growth and development: A multisite biomonitoring-based study in northern China.

BACKGROUND: Although animal experiments found that antibiotic exposure during early life increased adiposity, limited human epidemiological evidence is available for the effects of veterinary antibiotic exposure on children's growth and development. OBJECTIVE: This study was conducted to examine the body burden of fluoroquinolones in northern Chinese children and assess its association with growth and development. METHODS: After recruiting 233 children aged 0-15 years from 12 different sites in northern China in 2020, we measured urinary concentrations of 5 respective fluoroquinolones (fleroxacin, ofloxacin, norfloxacin, ciprofloxacin, and enrofloxacin) by high performance liquid chromatography. Categories of children's growth and development were identified based on the Z score of body mass index. The health risks of individual and combined antibiotic exposure were estimated by the hazard quotient (HQ) and hazard index (HI), respectively. The association between children's growth and development with antibiotic concentrations was evaluated via multiple logistic regression analysis. RESULTS: In total, 4 antibiotics, fleroxacin, ofloxacin, ciprofloxacin, and enrofloxacin, were found in urine samples of northern Chinese children at an overall frequency of 57.08%. Due to diet and economic differences, antibiotic concentrations in urine samples differed by study area, and the highest concentrations were found in Tianjin, Henan, and Beijing. The percentage of the participants with HQ > 1 caused by ciprofloxacin exposure was 20.61%, and the HI values in 23.18% of samples exceeded 1, suggesting potential health risks. The odds ratio (95% confidence interval) of overweight or obesity risk of tertile 2 of enrofloxacin was 3.01 (1.12, 8.11), indicating an increase in overweight or obesity risk for children with middle-concentration enrofloxacin exposure. CONCLUSION: This is the first study to show a positive association of enrofloxacin internal exposure with overweight or obesity risk in children, demonstrating that more attention should be given to the usage and disposal of fluoroquinolones to safeguard children's health.

Phosphoinositide 3-kinase/Akt and its related signaling pathways in the regulation of tumor-associated macrophages polarization.

Tumor-associated macrophages (TAMs) are a type of functionally plastic immune cell population in tumor microenvironment (TME) and mainly polarized into two phenotypes: M2 and M1-like TAMs. The M2-like TAMs could stimulate tumor growth and metastasis, tissue remodeling and immune-suppression, whereas M1-like TAMs could initiate immune response to dampen tumor progression. TAMs with different polarization phenotypes can produce various kinds of cytokines, chemokines and growth factors to regulate immunity and inflammatory responses. It is an effective method to treat cancer through ameliorating TME and modulating TAMs by converting M2 into M1-like phenotype. However, intracellular signaling mechanisms underlying TAMs polarization are largely undefined. Phosphoinositide 3-kinase (PI3K)/Akt is an important signaling pathway participating in M2-like TAMs polarization, survival, growth, proliferation, differentiation, apoptosis and cytoskeleton rearrangement. In the present review, we analyzed the mechanism of TAMs polarization focusing on PI3K/Akt and its downstream mitogen­activated protein kinase (MAPK) as well as nuclear factor kappa B (NF-κB) signaling pathways, thus provides the first evidence of intracellular targets for cancer immunotherapy.

High Performance 3D Self-Supporting Cu-Bi Aerogels for Electrocatalytic Reduction of CO2 to Formate.

The electrocatalytic reduction of CO2 (CO2 RR) to CO, formate, methane, and other high-value compounds is a promising technique. However, current electrocatalysts suffer from drawbacks such as few active catalytic sites, poor selectivity and low stability, etc, which restrict the practical application. Although monatomic metal catalysts have been widely reported in recent years, high performance non-noble metal aerogels were rarely investigated for electrocatalytic CO2 RR. Herein, Cu-Bi aerogels with boosted CO2 RR activity were well constructed by a simple one-step self-assembly method. The resultant Cu1 Bi2 exhibits excellent CO2 RR activity with high faradaic efficiency (FE) of 96.57 % towards HCOOH at a potential of -0.9 V vs. RHE, and the FEHCOOH remains over 80.18 % in a wide potential window (-0.8 V to -1.2 V vs. RHE). It demonstrated that the enhanced CO2 RR activity of Cu-Bi aerogels could be attributed to the 3D self-supporting structure of the catalysis, synergistic effect, and low interfacial charge transfer resistance.

Adult Vanishing White Matter Disease with a Novel EIF2B4 Mutation.

Vanishing white matter disease (VWMD) is an autosomal recessive genetic disease characterised by progressive loss of white matter in both cerebral hemispheres. VWMD is caused by mutations in eukaryotic translation initiation factor 2B (EIF2B). The disease typically occurs in children. Ovarioleukodystrophies disease (OLD) is a special type of adult VWMD, associated with primary ovarian insufficiency. Herein, we report an adult woman with VWMD who had a novel EIF2B4 mutation. A 27-year woman presented with complaints of intermittent movement disorder of both upper extremities for 5 years and walking instability for 1 year. She had primary amenorrhea and infertility, low sex hormones, and a primordial uterus. MRI showed progressive loss of white matter in the brain. Whole-exome sequencing showed a novel EIF2B4 gene mutation: c.1441 (exon13) T>C. Therefore, a diagnosis of OLD, a special type of adult VWMD, was established. To our knowledge, this is a novel mutation and has not been reported till date. This report extends the mutation spectrum and phenotypic heterogeneity of VWMD. Key Words: Vanishing White matter, EIF2B, Primary ovarian insufficiency.

A sweet spot for macrophages: Focusing on polarization.

Macrophages are a type of functionally plastic cells that can create a pro-/anti-inflammatory microenvironment for organs by producing different kinds of cytokines, chemokines, and growth factors to regulate immunity and inflammatory responses. In addition, they can also be induced to adopt different phenotypes in response to extracellular and intracellular signals, a process defined as M1/M2 polarization. Growing evidence indicates that glycobiology is closely associated with this polarization process. In this research, we review studies of the roles of glycosylation, glucose metabolism, and key lectins in the regulation of macrophages function and polarization to provide a new perspective for immunotherapies for multiple diseases.

Identification of MMACHC and PROKR2 mutations causing coexistent cobalamin C disease and Kallmann syndrome in a young woman.

Cobalamin C (cblC) disease and Kallmann syndrome (KS) are rare hereditary diseases. To date, no report has described the coexistence of those two genetic disorders in the same patient, or an association between them. We report the case of a 23-year-old woman with cblC defect and KS. She first presented mild memory problems in puberty, which worsened in adulthood to progressive memory loss accompanied by slow and unsteady walking, slow response, inattention, cognitive impairment, insomnia, no sense of smell, and the lack of spontaneous puberty. Laboratory tests revealed gonadotropin deficiency, a low estrogen level, and remarkably elevated serum homocysteine and serum and urine organic acid levels. Whole-exome sequencing detected compound heterozygous variants in MMACHC [c.398_399del (p.Gln133Argfs*4) and c.482G > A (p.Arg161Gln)] and heterozygous variants in PROKR2 [c.337T > C (p.Tyr113His)]. Thus, clinical and genetic examinations confirmed the cblC disease and KS diagnoses. This report on coexisting cblC disease and KS caused by different pathogenic genes in a single patient enriches the clinical research on these two rare genetic diseases.

Occurrence and partition of organochlorine pesticides (OCPs) in water, sediment, and organisms from the eastern sea area of Shandong Peninsula, Yellow Sea, China.

To evaluate the occurrence and partition of organochlorine pesticides (OCPs), hexachlorocyclohexanes (HCHs) and dichlorodiphenyltrichloroethanes (DDTs), water, sediment, and organisms were sampled from the eastern sea area of Shandong Peninsula (Yellow Sea, China) across all four seasons in 2016. There were three OCP hotspots in the sediment, mainly caused by the transportation of lindane and dicofol from adjacent Swan Lake and Guhe River. Waterborne OCP levels were highest in winter and lowest in spring, without vertical variability, suggesting that the Yellow Sea Cold Water Mass was governing the spatio-temporal distribution of OCPs in seawater. There was substantial accumulation of HCHs and DDTs in organisms via sediment, as indicated by the relatively low fraction of sedimental fugacity, high bio-sediment accumulation factor, and a positive linear correlation between logΣHCHs and trophic level. This is the first study that has focused on the accumulation of OCPs in entire sediment-seawater-organism system involving multi-phyla of species.

Association of PTEN Gene SNPs rs2299939 With PFS in Patients With Small Cell Lung Cancer Treated With Early Radiotherapy.

Lung cancer has higher morbidity and mortality than most cancers. It is common that there are some phenomenons of secondary drug resistance, radiotherapy resistance and poor prognosis during the treatment of small cell lung cancer (SCLC). Recent studies revealed that the single-nucleotide polymorphisms (SNPs) are associated with the curative effect among patients with the same pathological type and stage. Our study analyzed the start time of radiotherapy and the relationship between PTEN gene rs2299939 polymorphisms and survival time among 116 SCLC patients. The results showed that early radiotherapy significantly improved the time of survival in patients compared with late radiotherapy ( P = 0.029). Simultaneously, the study found that patients with the rs2299939 AA genotype showed significant sensitivity to both early and late radiotherapy, but early radiotherapy is better. The median survival time of CC genotype patients was 12 months in the early radiotherapy group while it was 9 months in the late radiotherapy group, thus recommending early radiotherapy among these patients. In addition, it was found that rs2299939 could regulate the expression of related genes in peripheral blood and lung tissues by eQTL analysis. This study revealed that the early radiotherapy could prolong the PFS of SCLC and shall be performed in SCLC treatment.