Factors associated with nocturnal and diurnal glycemic variability in patients with type 2 diabetes: a cross-sectional study.

PURPOSE: There is little information on factors that influence the glycemic variability (GV) during the nocturnal and diurnal periods. We aimed to examine the relationship between clinical factors and GV during these two periods. METHODS: This cross-sectional study included 134 patients with type 2 diabetes. 24-h changes in blood glucose were recorded by a continuous glucose monitoring system. Nocturnal and diurnal GV were assessed by standard deviation of blood glucose (SDBG), coefficient of variation (CV), and mean amplitude of glycemic excursions (MAGE), respectively. Robust regression analyses were performed to identify the factors associated with GV. Restricted cubic splines were used to determine dose-response relationship. RESULTS: During the nocturnal period, age and glycemic level at 12:00 A.M. were positively associated with GV, whereas alanine aminotransferase was negatively associated with GV. During the diurnal period, homeostatic model assessment 2-insulin sensitivity (HOMA2-S) was positively associated with GV, whereas insulin secretion-sensitivity index-2 (ISSI2) was negatively associated with GV. Additionally, we found a J-shape association between the glycemic level at 12:00 A.M. and MAGE, with 9.0 mmol/L blood glucose level as a cutoff point. Similar nonlinear associations were found between ISSI2 and SDBG, and between ISSI2 and MAGE, with ISSI2 value of 175 as a cutoff point. CONCLUSION: Factors associated with GV were different between nocturnal and diurnal periods. The cutoff points we found in this study may provide the therapeutic targets for beta-cell function and pre-sleep glycemic level in clinical practice.

Dose-related effects of early-life intake of sn-2 palmitate, a specific positionally distributed human milk fatty acid, on the composition and metabolism of the intestinal microbiota.

sn2 Palmitate in human milk plays an important role in the physiological health of infants by reducing mineral loss, improving stool hardness, and relieving constipation. Also, sn-2 palmitate modulates intestinal microbiota. However, it remains unclear whether the effects of sn-2 palmitate on infant gut microbiota are dose-dependent. In this study, we investigated the effects of low, medium, and high doses (600, 1,800, and 5,400 mg/kg body weight, respectively) of sn-2 palmitate on the structure, composition, and metabolic function of intestinal microbes in mice. Our results showed that high doses of sn-2 palmitate significantly modulated α- and ß-diversity of the intestinal microbiota. The relative abundance of Lachnospiraceae_NK4A136_group decreased with increasing doses of sn-2 palmitate. In contrast, the abundances of Bacteroidetes phylum, Bacteroides, uncultured_Lachnospiraceae, and uncultured_Muribaculaceae were positively correlated with sn-2 palmitate doses. The number of genes predicted encoding autophagy-yeast, phospholipase D signaling pathway, and pentose and glucuronate interconversion metabolic functions of intestinal microbiota increased with increasing doses of sn-2 palmitate. In addition, low and medium doses of sn-2 palmitate significantly upregulated the arginine and proline metabolic pathways, and high doses of sn-2 palmitate significantly increased purine metabolism. Our results revealed that the effects of sn-2 palmitate intake early in life on the composition and metabolism of the intestinal microbiota of mice showed dose-related differences. The study is expected to provide a scientific basis for the development of infant formulas.

Anti-Cancer Effects of Disulfiram in Cervical Cancer Cell Lines Are Mediated by Both Autophagy and Apoptosis.

Disulfiram (DSF), which is used to treat alcohol dependence, has been reported to have anticancer effects in various malignant tumors. We studied the anti-cancer effects and mechanism of action of DSF on cervical cancer cell lines HeLa and SiHa. The anti-cancer effects of DSF were confirmed in vivo using a xenograft tumor model. The anti-cancer effects of DSF in human head and neck squamous cell carcinoma were found to be copper (Cu)-dependent. The anti-tumor effects of DSF/Cu were time- and dose-dependent and were mediated by both autophagy and apoptosis. DSF/Cu shows stronger cytotoxicity to adenocarcinoma cell lines with higher malignant behavior, and valosin-containing protein (VCP) is its potential target. The cytotoxic effect of DSF/Cu against cervical cancer cell lines in vitro was mediated by apoptosis and autophagy simultaneously. Analysis of the clinical relevance of DSF/Cu on a xenograft animal model showed that DSF markedly stimulated tumor necrosis. DSF may contribute to improved survival of patients with cervical cancer. The antitumor characteristic of DSF can be used in the development of a new drug for advanced and refractory patients with cervical cancer.

[ABC prognostic classification and MELD 3.0 and COSSH-ACLF â ¡ prognostic evaluation in acute-on-chronic liver failure].

Objective: To investigate the ABC prognostic classification and the updated version of Model for End-stage Liver Disease (MELD) score 3.0 and Chinese Group on the Study of Severe Hepatitis B ACLF Ⅱ score (COSSH-ACLF Ⅱ score) to evaluate the prognostic value in acute-on-chronic liver failure (ACLF). Methods: ABC classification was performed on a 1 409 follow-up cohorts. The area under the receiver operating characteristic curve (AUROC) was used to analyze MELD, MELD 3.0, COSSH-Ⅱ and COSSH-Ⅱ score after 3 days of hospitalization (COSSH-Ⅱ-3d). The prognostic predictive ability of patients were evaluated for 360 days, and the prediction differences of different classifications and different etiologies on the prognosis of ACLF were compared. Results: The survival curve of 1 409 cases with ACLF showed that the difference between class A, B, and C was statistically significant, Log Rank (Mantel-Cox) χ2=80.133, P<0.01. Compared with class A and C, χ2=76.198, P<0.01, the difference between class B and C, was not statistically significant χ2=3.717, P>0.05. AUROC [95% confidence interval (CI)] analyzed MELD, MELD 3.0, COSSH-Ⅱ and COSSH-Ⅱ-3d were 0.644, 0.655, 0.817 and 0.839, respectively (P<0.01). COSSH-Ⅱ had better prognostic predictive ability with class A ACLF and HBV-related ACLF (HBV-ACLF) for 360-days, and AUROC (95% CI) were 0.877 and 0.881, respectively (P<0.01), while MELD 3.0 prognostic predictive value was not better than MELD. Conclusion: ACLF prognosis is closely related to ABC classification. COSSH-Ⅱ score has a high predictive value for the prognostic evaluation of class A ACLF and HBV-ACLF. COSSH-Ⅱ score has a better prognostic evaluation value after 3 days of hospitalization, suggesting that attention should be paid to the treatment of ACLF in the early stage of admission.

Scaling Law Describes the Spin-Glass Response in Theory, Experiments, and Simulations.

The correlation length ξ, a key quantity in glassy dynamics, can now be precisely measured for spin glasses both in experiments and in simulations. However, known analysis methods lead to discrepancies either for large external fields or close to the glass temperature. We solve this problem by introducing a scaling law that takes into account both the magnetic field and the time-dependent spin-glass correlation length. The scaling law is successfully tested against experimental measurements in a CuMn single crystal and against large-scale simulations on the Janus II dedicated computer.

[Clinical analysis of 2 820 cases of drug-induced liver injury].

Objective: To investigate the clinical characteristics, incidence trend, underlying diseases, causative drug and prognosis of drug-induced liver injury (DILI), so as to provide basis for its prevention and treatment. Methods: A retrospective study was conducted on 2 820 DILI cases who were admitted to our hospital from January 2002 to December 2015, and their clinical characteristics, incidence trends, underlying related diseases, causative drug, treatment and outcome were analyzed. Results: Among 2 820 DILI cases, the ratio of male to female was 1:1.44, and the age was (44.00±16.32) years old. According to the clinical classification of DILI, there were 2 353 cases (83.43%) of hepatocyte injury, 353 cases (12.51%) of cholestatic type and 114 cases (4.04%) of mixed type. In the three clinical classification of DILI, there was no statistically significant difference in the ratio of male to female (χ(2) = 3.032, P > 0.05). However, the difference in the ratio of male to female between different age groups was statistically significant (χ(2) = 48.367, P < 0.001). Among the patients with liver disease and acute liver disease admitted to our hospital from January 2002 to December 2015, the proportion of DILI and acute DILI showed an overall upward trend. The main underlying related diseases of 2 820 DILI cases were fever (15.14%), skin diseases (11.84%), cardiovascular and cerebrovascular diseases (11.17%). Chinese herbal patent medicines (37.49%), antibiotics (15.85%), antipyretic-analgesics (14.37%), and so on were the main causative drugs involved, and the prognostic differences among the three clinical classifications of DILI in terms of cure, improvement, ineffectiveness, and death were statistically significant (H = 61.300, P < 0.001). Conclusion: In recent years, among the patients with liver disease in our hospital, the proportion of DILI has shown an obvious upward trend, involving a variety of underlying diseases and causative drugs, and thus it needs clinical attention.

[Experts consensus on the management of delirium in critically ill patients].

To establish the experts consensus on the management of delirium in critically ill patients. A special committee was set up by 15 experts from the Chinese Critical Hypothermia-Sedation Therapy Study Group. Each statement was assessed based on the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) principle. Then the Delphi method was adopted by 36 experts to reassess all the statements. (1) Delirium is not only a mental change, but also a clinical syndrome with multiple pathophysiological changes. (2) Delirium is a form of disturbance of consciousness and a manifestation of abnormal brain function. (3) Pain is a common cause of delirium in critically ill patients. Analgesia can reduce the occurrence and development of delirium. (4) Anxiety or depression are important factors for delirium in critically ill patients. (5) The correlation between sedative and analgesic drugs and delirium is uncertain. (6) Pay attention to the relationship between delirium and withdrawal reactions. (7) Pay attention to the relationship between delirium and drug dependence/withdrawal reactions. (8) Sleep disruption can induce delirium. (9) We should be vigilant against potential risk factors for persistent or recurrent delirium. (10) Critically illness related delirium can affect the diagnosis and treatment of primary diseases, and can also be alleviated with the improvement of primary diseases. (11) Acute change of consciousness and attention deficit are necessary for delirium diagnosis. (12) The combined assessment of confusion assessment method for the intensive care unit and intensive care delirium screening checklist can improve the sensitivity of delirium, especially subclinical delirium. (13) Early identification and intervention of subclinical delirium can reduce its risk of clinical delirium. (14) Daily assessment is helpful for early detection of delirium. (15) Hopoactive delirium and mixed delirium are common and should be emphasized. (16) Delirium may be accompanied by changes in electroencephalogram. Bedside electroencephalogram monitoring should be used in the ICU if conditions warrant. (17) Pay attention to differential diagnosis of delirium and dementia/depression. (18) Pay attention to the role of rapid delirium screening method in delirium management. (19) Assessment of the severity of delirium is an essential part of the diagnosis of delirium. (20) The key to the management of delirium is etiological treatment. (21) Improving environmental factors and making patient comfort can help reduce delirium. (22) Early exercise can reduce the incidence of delirium and shorten the duration of delirium. (23) Communication with patients should be emphasized and strengthened. Family members participation can help reduce the incidence of delirium and promote the recovery of delirium. (24) Pay attention to the role of sleep management in the prevention and treatment of delirium. (25) Dexmedetomidine can shorten the duration of hyperactive delirium or prevent delirium. (26) When using antipsychotics to treat delirium, we should be alert to its effect on the heart rhythm. (27) Delirium management should pay attention to brain functional exercise. (28) Compared with non-critically illness related delirium, the relief of critically illness related delirium will not accomplished at one stroke. (29) Multiple management strategies such as ABCDEF, eCASH and ESCAPE are helpful to prevent and treat delirium and improve the prognosis of critically ill patients. (30) Shortening the duration of delirium can reduce the occurrence of long-term cognitive impairment. (31) Multidisciplinary cooperation and continuous quality improvement can improve delirium management. Consensus can promote delirium management in critically ill patients, optimize analgesia and sedation therapy, and even affect prognosis.

Functional analysis of p.Ala253_Leu254insAsn mutation in PLS3 responsible for X-linked osteoporosis.

Mutations in Plastin-3 (PLS3) have been identified as a cause of X-linked osteoporosis. To reveal the molecular mechanism of PLS3 on osteoporosis, we characterized the p.Ala253_Leu254insAsn mutation in PLS3. We first identified Lymphocyte cytosolic protein 1 (LCP1) as a binding partner of PLS3 and the mutation disrupted the interaction between them. We then confirmed the roles of PLS3 and LCP1 in the regulation of intracellular Ca2+ , which was weakened by the mutant PLS3. Moreover, the interaction between PLS3 and LCP1 was enhanced under a low concentration of extracellular Ca2+ . However, the mutation in PLS3 weakened the responsiveness. The reduced regulation on Ca2+ caused by p.Ala253_Leu254insAsn may be the possible molecular mechanism of osteoporosis.

A mixture of Lactobacillus species isolated from traditional fermented foods promote recovery from antibiotic-induced intestinal disruption in mice.

AIMS: This study evaluated the antibiotic-induced changes in microbial ecology, intestinal dysbiosis and low-grade inflammation; and the combined effect of four different Lactobacillus species on recovery of microbiota composition and improvement of gut barrier function in mice. METHODS AND RESULTS: Administration of the antibiotic ampicillin for 2 weeks decreased microbial community diversity, induced caecum tumefaction and increased gut permeability in mice. Application of a probiotic cocktail of four Lactobacillus species (JUP-Y4) modulated the microbiota community structure and promoted the abundance of potentially beneficial bacteria such as Akkermansia. Ampicillin administration led to a decline in Bacteroidetes from 46·6 ± 3·91% to 0·264 ± 0·0362%; the addition of JUP-Y4 restored this to 41·4 ± 2·87%. This probiotic supplementation was more effective than natural restoration, where the levels of Bacteroidetes were only restored to 29·3 ± 2·07%. Interestingly, JUP-Y4 treatment was more effective in the restoration of microbiota in faecal samples than in caecal samples. JUP-Y4 also significantly reduced the levels of d-lactate and endotoxin (lipopolysaccharide, LPS) in the serum of mice, and increased the expression of tight-junction proteins while reducing the production of inflammatory cytokines (TNF-α, IL-6, MCP-1, IFN-γ and IL-1ß) in the ileum and the colon of antibiotic-treated mice. CONCLUSIONS: JUP-Y4 not only promoted recovery from antibiotic-induced gut dysbiosis, but also enhanced the function of the gut barrier, reduced inflammation and lowered levels of circulating endotoxin in mice. SIGNIFICANCE AND IMPACT OF THE STUDY: Consumption of a mixture of Lactobacillus species may encourage faster recovery from antibiotic-induced gut dysbiosis and gut microbiota-related immune disturbance.

Association between interleukin-10 gene polymorphisms and susceptibility to diabetic nephropathy in a Chinese population.

In this study, we investigated the association between the interleukin (IL)-10 -592C/A, -819C/T, and -1082G/A genetic variations and susceptibility to diabetic nephropathy in a Chinese population. The IL-10 -592C/A, -819C/T, and -1082G/A polymorphisms were genotyped in diabetic nephropathy patient and control samples by polymerase chain reaction-restriction fragment length polymorphism. The results were then statistically analyzed using SPSS 17.0. The results of the χ(2) test revealed a significant difference in the frequencies of the GG, GA, and AA genotypes of IL-10 -1082G/A between patients with diabetic nephropathy and control subjects (χ(2) = 10.03, P = 0.007). Unconditional logistic regression analysis revealed that the AA genotype of IL-10 -1082G/A significantly increased the susceptibility to diabetic nephropathy [adjusted odds ratio (OR) = 2.52, 95% confidence interval (CI) = 1.31-4.82] compared to the wild-type genotype. Moreover, the A allele of this polymorphism was associated with an increased risk of diabetic nephropathy compared to the G allele (adjusted OR = 1.51, 95%CI = 1.15-1.99). However, the IL-10 -819T/C and -592A/C genetic polymorphisms did not increase the risk of diabetic nephropathy. In conclusion, the IL-10 -1082G/A polymorphism was found to be correlated with the development of diabetic nephropathy.

Monoenergetic positronium emission from metal-organic framework crystals.

Recently it has been discovered that positronium (Ps), after forming in metal-organic framework (MOF) crystals, is emitted into vacuum with a high efficiency and low energy that can only be explained by its propagating as delocalized Bloch states. We show that the Ps atoms are emitted from MOFs in a series of narrow energy peaks consistent with Ps at Bloch-state energy minima being emitted adiabatically into the vacuum. This implies that the Ps emission energy spectra can be directly compared with calculations to obtain detailed information about the Ps band structure in the MOF crystal. The narrow energy width of the lowest energy Ps peak from one MOF sample (2-Methylimidazole zinc salt ZIF-8) suggests it originates from a polaronic Ps surface state. Other peaks can be assigned to Ps with an effective mass of about twice that of bare Ps. Given the immense catalog of available MOF crystals, it should be possible to tune the Ps properties to make vastly improved sources with high production efficiency and a narrow energy spread, for use in fundamental physics experiments.

Exceptional material requirement for reproduction in mouse oocytes.

Limited information on oocytes and fertilization prevents the efficient therapy of patients with infertility. The most important reason for this lack of understanding is a deficiency in research dedicated to oocytes and fertilization. Currently, we are concerned with the role of nutrition in the process of oocyte development to better understand the relationship between nutrition and infertility. The aim of this study was to explore the relationship between some exceptional materials and infertility to elucidate the role of these materials in oocyte development. We used proteomic analysis to identify numerous nutrition-related proteins in three developmental stages: the germinal vesicle stage, the metaphase II-arrested stage, and the fertilized oocyte-zygote stage. Specific proteins were abundantly expressed during the three stages. These proteins included astacin-like metalloendopeptidase, selenium-binding proteins, and other proteins involved in metabolic and signaling pathways. Other proteins were involved in the citrate cycle, the electron transport chain, the urea cycle, fatty acid metabolism, and the insulin signaling pathway. Almost all these proteins exhibited different expression levels in the three stages. The results of the present study provide a better understanding of the molecular mechanisms of early embryonic development and suggest new treatment methods for infertility.

Development and characterization of novel expressed sequence tag-derived simple sequence repeat markers in Hevea brasiliensis (rubber tree).

Cultivated clones of Hevea brasiliensis have a narrow genetic base. In order to broaden the genetic base, it is first necessary to investigate the genetic diversity of wild populations. Expressed sequence tag-simple sequence repeat (EST-SSR) markers were developed to investigate the genetic diversity of Hevea populations. Four hundred and thirty microsatellites were identified and 148 primers were designed to amplify the loci. Twenty-nine primer pairs were synthesized and evaluated for their ability to detect genetic polymorphisms among 40 wild accessions of H. brasiliensis. Twenty-one of the 29 loci were polymorphic. The number of alleles per locus in the 40 accessions ranged from 2 to 7. H(O) and H(E) at each locus ranged from 0.0000 to 0.9000 and from 0.0000 to 0.8704, respectively. All 21 loci could amplify in H. brasiliensis, H. pauciflora, H. nitida, H. spruceana, and H. camargoana. The EST-SSR primers developed herein can be used in genetic diversity and structure studies in H. brasiliensis.

Long-term effects of choline on productive performance and egg quality of brown-egg laying hens.

A total of five hundred forty 19-wk-old HyLine Brown hens were used to study the long-term effects of increasing choline with 0 (control), 425, 850, 1,700, 3,400, and 6,800 mg/kg of corn-soybean meal-based diets on productive performance and egg quality. Phase 1 was from 19 to 58 wk, and phase 2 was from 59 to 68 wk. During the whole experimental period, dietary choline had no significant effects on feed intake, egg weight, and egg mass (P > 0.05). During phase 1, egg production decreased linearly (P < 0.05) and feed conversion ratio (FCR) tended to increase linearly (P = 0.057) with increasing choline level in the diet. Moreover, BW decreased both linearly (P < 0.01) and quadratically (P < 0.05) as choline increased from 0 to 6,800 mg/kg. No significant treatment effects were found for shell thickness and shell strength of eggs (P > 0.05). However, albumen height and Haugh units increased linearly (P < 0.01 and P < 0.05, respectively) as choline increased during phase 2. Compared with the control group, diets supplemented with 425 or 850 mg of choline/kg significantly (P < 0.01) improved yolk color during phase 1. This study indicates that a dietary choline level of no more than 700 mg/kg is sufficient to maintain egg production. The effect of choline on egg quality was minimal when hens were fed a corn-soybean meal-based diet from 19 to 68 wk of age.

Downregulation of miR-181a upregulates sirtuin-1 (SIRT1) and improves hepatic insulin sensitivity.

AIMS/HYPOTHESIS: Sirtuin-1 (SIRT1) is a potential therapeutic target to combat insulin resistance and type 2 diabetes. This study aims to identify a microRNA (miRNA) targeting SIRT1 to regulate hepatic insulin sensitivity. METHODS: Luciferase assay combined with mutation and immunoblotting was used to screen and verify the bioinformatically predicted miRNAs. miRNA and mRNA levels were measured by real-time PCR. Insulin signalling was detected by immunoblotting and glycogen synthesis. Involvement of SIRT1 was studied with adenovirus, inhibitor and SIRT1-deficient hepatocytes. The role of miR-181a in vivo was explored with adenovirus and locked nucleic acid antisense oligonucleotides. RESULTS: miR-181a targets the 3' untranslated region (3'UTR) of Sirt1 mRNA through a miR-181a binding site, and downregulates SIRT1 protein abundance at the translational level. miR-181a is increased in insulin-resistant cultured hepatocytes and liver, and in the serum of diabetic patients. Overexpression of miR-181a decreases SIRT1 protein levels and activity, and causes insulin resistance in hepatic cells. Inhibition of miR-181a by antisense oligonucleotides increases SIRT1 protein levels and activity, and improves insulin sensitivity in hepatocytes. Ectopic expression of SIRT1 abrogates the effect of miR-181a on insulin sensitivity, and inhibition of SIRT1 activity or SIRT1 deficiency markedly attenuated the improvement in insulin sensitivity induced by antisense miR-181a. In addition, overexpression of miR-181a by adenovirus impairs hepatic insulin signalling, and intraperitoneal injection of locked nucleic acid antisense oligonucleotides for miR-181a improves glucose homeostasis in diet-induced obesity mice. CONCLUSIONS/INTERPRETATION: miR-181a regulates SIRT1 and improves hepatic insulin sensitivity. Inhibition of miR-181a might be a potential new strategy for treating insulin resistance and type 2 diabetes.

Osteogenesis and angiogenesis of a bulk metallic glass for biomedical implants.

Implantation is an essential issue in orthopedic surgery. Bulk metallic glasses (BMGs), as a kind of novel materials, attract lots of attentions in biological field owing to their comprehensive excellent properties. Here, we show that a Zr61Ti2Cu25Al12 (at. %) BMG (Zr-based BMG) displays the best cytocompatibility, pronounced positive effects on cellular migration, and tube formation from in-vitro tests as compared to those of commercial-pure titanium and poly-ether-ether-ketone. The in-vivo micro-CT and histological evaluation demonstrate the Zr-based BMG can significantly promote a bone formation. Immunofluorescence tests and digital reconstructed radiographs manifest a stimulated effect on early blood vessel formation from the Zr-based BMG. Accordingly, the intimate connection and coupling effect between angiogenesis and osteogenesis must be effective during bone regeneration after implanting Zr-based BMG. Dynamic gait analysis in rats after implanting Zr-based BMG demonstrates a tendency to decrease the pain level during recovery, simultaneously, without abnormal ionic accumulation and inflammatory reactions. Considering suitable mechanical properties, we provide a realistic candidate of the Zr61Ti2Cu25Al12 BMG for biomedical applications.

Cancer cell-intrinsic STING is associated with CD8 + T-cell infiltration and might serve as a potential immunotherapeutic target in hepatocellular carcinoma.

PURPOSE: The activation of stimulator of interferon genes (STING) pathway triggers the antitumor immunity by CD8 + T cells. However, the differentiated antitumor effects of STING activation in different cell types is still unclear. We aimed to investigate the expression and potential prognostic value of cancer cell-intrinsic STING in hepatocellular carcinoma (HCC), and whether STING could be a potential immunotherapeutic target of HCC was then evaluated. METHODS: We separately assessed the expression of STING in cancer cells and infiltrating immune cells in HCC tissues. The independent clinicopathological factors associated with survival outcomes were evaluated by the multivariable analysis. The HCC orthotopic mice model were used to confirm the immunotherapeutic effects of STING agonists, and CD8 + T-cell infiltration level was analyzed through immunofluorescence and flow cytometry. RESULTS: The expression of cancer cell-intrinsic STING was significantly reduced in HCC compared with adjacent tissues. Patients with low levels of cancer cell-intrinsic STING expression was associated with increased tumor volume (P = 0.009), higher serum AFP levels (P = 0.028), and decreased CD8 + T-cell infiltration (P = 0.002). Low levels of cancer cell-intrinsic STING expression indicated a poor overall survival (OS) and disease-free survival (DFS). Multivariate analysis demonstrated that low levels of cancer cell-intrinsic STING expression was an independent prognostic factor. Additionally, cancer cell-intrinsic STING expression was positively related with CD8 + T-cell infiltration levels in HCC patients (r = 0.308; P = 0.001). When mice with orthotopic HCC tumors treated with STING agonists, tumor growth was significantly reduced with enhanced levels of CD8 + T-cell infiltration. CONCLUSION: Cancer cell-intrinsic STING might affect HCC tumor progression through enhancing CD8 + T-cell infiltration and can be an immunotherapeutic target for HCC.

Does endoplasmic reticulum stress stimulate the apoptosis of granulosa cells in polycystic ovary syndrome?

The aim of this study was to determine whether endoplasmic reticulum (ER) stress is involved in the apoptosis of granulosa cells in patients with polycystic ovary syndrome (PCOS). A total of 116 patients undergoing in vitro fertilization/intracytoplasmic sperm injection cycles at the Binzhou Medical University Hospital IVF Center between September 2019 and January 2020 were enrolled in the study. Apoptosis of the granulosa cells in each patient was analyzed using flow cytometry, and progesterone and estrogen levels in the cell-culture fluid were measured by enzyme-linked immunosorbent assay. The expressions of X-box-binding protein 1 (XBP1(s)), activating transcription factor 6 (ATF6), C/EBP homologous protein (CHOP), B-cell CLL/lymphoma 2 protein (Bcl-2), and Bcl-2 associated X protein (Bax) at the gene or protein level were analyzed using quantitative real-time polymerase chain reaction and Western blotting, respectively. In patients with PCOS, body mass index and basal serum concentrations of luteinizing hormone, testosterone (T), and anti-Mullerian hormone significantly increased (P < 0.05). The number of oocytes retrieed and the rate of clinical pregnancy after the first frozen embryo transfer also significantly increased (P < 0.05). Although apoptosis rate in the granulosa cells significantly increased in patients with PCOS, progesterone (P) and estrogen (E2) levels in the cell-culture fluid significantly decreased (P < 0.05). The apoptosis of granulosa cells was also found to affect blastocyst formation. Furthermore, the messenger ribonucleic acid (mRNA) expressions of XBP1(s), ATF6, CHOP, and Bax significantly increased in patients with PCOS, while that of Bcl-2 significantly decreased (P < 0.05). The protein expressions of CHOP and Bax significantly increased in patients with PCOS, while that of Bcl-2 significantly decreased (P < 0.05). After treatment of the granulosa cells with tauroursodeoxycholic acid, apoptosis rate and mRNA or protein expressions of XBP1(s), CHOP, and Bax significantly decreased, while the expression of Bcl-2 and levels of progesterone and estrogen significantly increased (P < 0.05). We conclude that ER stress could induce the apoptosis of granulosa cells in patients with PCOS. Cell apoptosis may decrease the number of blastocysts formed.

Isolation of Photobacterium sp. LuB-1 and its application in rapid assays for chemical toxicants in water.

AIMS: To isolate marine bacteria with strong bioluminescence in a wide range of NaCl concentration, especially at low salt conditions. METHODS AND RESULTS: A luminous bacterium named LuB-1 was isolated from China. It was identified by biochemical analysis and phylogenetic analysis based on the 16S rRNA gene and designated as Photobacterium sp. The isolate is capable of emitting strong and stable luminescence in a wide range of NaCl concentration from 0.2 to 5% (w/v). For most toxic agents tested in this study, the response of LuB-1 was better than that of MicrotoxVibrio fischeri under both low salt (0.9% NaCl) and high salt (2.0% NaCl) conditions. CONCLUSION: The strain LuB-1 had an obvious predominance of bioluminescence in a wide range of NaCl concentration and better response for heavy metal pollutants and some organic toxicants in both low and high salt toxicity test systems. SIGNIFICANCE AND IMPACT OF THE STUDY: Because of its good sensitivity in a wide range of salt concentration, the strain LuB-1 should have its unique advantage in rapid assay for toxicants in water with different salt concentrations.

Whale Optimization Algorithm for Multiconstraint Second-Order Stochastic Dominance Portfolio Optimization.

In the field of asset allocation, how to balance the returns of an investment portfolio and its fluctuations is the core issue. Capital asset pricing model, arbitrage pricing theory, and Fama-French three-factor model were used to quantify the price of individual stocks and portfolios. Based on the second-order stochastic dominance rule, the higher moments of return series, the Shannon entropy, and some other actual investment constraints, we construct a multiconstraint portfolio optimization model, aiming at comprehensively weighting the returns and risk of portfolios rather than blindly maximizing its returns. Furthermore, the whale optimization algorithm based on FTSE100 index data is used to optimize the above multiconstraint portfolio optimization model, which significantly improves the rate of return of the simple diversified buy-and-hold strategy or the FTSE100 index. Furthermore, extensive experiments validate the superiority of the whale optimization algorithm over the other four swarm intelligence optimization algorithms (gray wolf optimizer, fruit fly optimization algorithm, particle swarm optimization, and firefly algorithm) through various indicators of the results, especially under harsh constraints.