Qualities of Older Adults' Family and Friendship Relationships and Their Association with Life Satisfaction.

While family and friendship relationship qualities are associated with life satisfaction, evidence on how these types of relationships interact to contribute to older adults' life satisfaction is sparse. This study examined how family and friendship relationship qualities may be supportive of (compensatory) or conflict with (competing) older adults' life satisfaction. We adopted a cross-sectional design to analyze data from the Health and Retirement Study (n = 1178, females = 54.8%, mean age = 67.9 years, SD = 9.3 years) to examine compensatory (as in social support) and competing (as in social strain) qualities of family and friendship social relationships and their association with life satisfaction in older adults. For greater explanatory power, we also controlled for life satisfaction by sociodemographic variables of age, gender, education, self-reported general health, physical health and activity, depression, and personality traits. Our findings indicate that the spouse/partner support relationship contributes to older adults' life satisfaction overall and is associated with greater social support and less social strain. Friendship support is associated with improved life satisfaction for older adults reporting spouse/partner strain. Relationship support for the life satisfaction of older adults should consider their need for social support from their social network while minimizing the risk of social strain from adversarial relationships in life situations.

SYT7 regulates the progression of chronic lymphocytic leukemia through interacting and regulating KNTC1.

BACKGROUND: Chronic lymphocytic leukemia (CLL) is one of the most frequent occurring types of leukemia. It typically occurs in elderly patients and has a highly variable clinical course. At present, the molecular mechanism driving the pathogenesis and progression of CLL is not fully understood. The protein Synaptotagmin 7 (SYT7) encoded by the SYT7 gene has been found to be closely related to the development of various solid tumors, but its role in CLL is unclear. In this study, we investigated the function and molecular mechanism of SYT7 in CLL. METHODS: The expression level of SYT7 in CLL was determined by immunohistochemical staining and qPCR. The role of SYT7 in promoting CLL development was verified by in vivo and in vitro experiments. The molecular mechanism of SYT7 in CLL was elucidated by methods such as GeneChip analysis and Co-immunoprecipitation assay. RESULTS: Malignant behaviors such as proliferation, migration, and anti-apoptosis of CLL cells were significantly inhibited after SYT7 gene knockdown. In contrast, SYT7 overexpression promoted CLL development in vitro. Consistently, the knockdown of SYT7 also inhibited xenograft tumor growth of CLL cells. Mechanistically, SYT7 promoted CLL development by inhibiting SYVN1-mediated KNTC1 ubiquitination. The KNTC1 knockdown also attenuated the effects of SYT7 overexpression on development of CLL. CONCLUSIONS: SYT7 regulates the progression of CLL through SYVN1-mediated KNTC1 ubiquitination, which has potential value for molecular targeted therapy of CLL.

Targeting efficacy of spironolactone in patients with heart failure with preserved ejection fraction: the TOPCAT study.

AIMS: We aimed to explore the heterogeneous treatment effects (HTEs) for spironolactone treatment in patients with Heart failure with preserved ejection fraction (HFpEF) and examine the efficacy and safety of spironolactone medication, ensuring a better individualized therapy. METHODS AND RESULTS: We used the causal forest algorithm to discover the heterogeneous treatment effects (HTEs) from patients in the Treatment of Preserved Cardiac Function Heart Failure with an Aldosterone Antagonist (TOPCAT) trial. Cox regressions were performed to assess the hazard ratios (HRs) of spironolactone medication for cardiovascular death and drug discontinuation in each group. The causal forest model revealed three representative covariates and participants were partitioned into four subgroups which were Group 1 (baseline BMI ≤ 31.71 kg/m2 and baseline ALP ≤ 80 U/L, n = 759); Group 2 (BMI ≤ 31.71 kg/m2 and ALP > 80 U/L, n = 1088); Group 3 (BMI > 31.71 kg/m2 , and WBC ≤ 6.6 cells/µL, n = 633); Group 4 (BMI > 31.71 kg/m2 and WBC > 6.6 cells/µL, n = 832), respectively. In the four subgroups, spironolactone therapy reduced the risk of cardiovascular death in high-risk group (Group 4) with both high BMI and WBC count (HR: 0.76; 95% CI 0.58 to 0.99; P = 0.045) but increased the risk in low-risk group (Group 1) with both low BMI and ALP (HR: 1.45; 95% CI 1.02 to 2.07; P = 0.041; P for interaction = 0.020) but showed similar risk of drug discontinuation (P for interaction = 0.498). CONCLUSION: Our study manifested the HTEs of spironolactone in patients with HFpEF. Spironolactone treatment in HFpEF patients is feasible and effective in patients with high BMI and WBC while harmful in patients with low BMI and ALP. Machine learning model could be meaningful for improved categorization of patients with HFpEF, ensuring a better individualized therapy in the clinical setting.

Monoclonal gammopathy of undetermined significance (MGUS) characterized by refractory lower gastrointestinal postoperative bleeding with coagulopathy.

Bleeding is a common complication after lower gastrointestinal surgery, and cases due to coagulation dysfunction are rare. The current authors encountered a 54-year-old Chinese man with refractory bleeding after endoscopic rectal polypectomy, and multiple endoscopic and surgical interventions failed to control that bleeding. An APTT mixing test could not be corrected and there was no evidence of autoimmune-related disease, so the presence of nonspecific antibodies was considered. After empiric therapy with a cyclophosphamide and glucocorticoid, APTT was corrected and gastrointestinal bleeding stopped. Based on laboratory results and therapeutic results, the patient was ultimately diagnosed with prolonged APTT induced by monoclonal gammopathy of undetermined significance (MGUS). MGUS and coagulopathy characterized by a prolonged APTT has rarely been reported. Here, studies noting elevated monoclonal immunoglobulins and coagulopathy have been reviewed. If a prolonged APTT of undetermined significance cannot be corrected with an APTT mixing test and if autoimmune-related factors are excluded, then plasma cell-related diseases such as MGUS need to be considered.

[Distribution, Migration, and Transformation Mechanism of Labile Phosphorus in Sediments of Xixi River Estuary, Xiamen].

To explore the effect of manganese, iron, and sulfur geochemistry on the distribution of labile phosphorus in different estuarine areas, the diffusion gradient in thin-film (DGT) sampling technique was used for in-situ high-resolution monitoring of available phosphorus (DGT-P), manganese, iron, and sulfur in sediments from Xixi River estuary in Xiamen. The results showed that the distribution of DGT-P in the vertical profile was closely related to the redox transformation of iron and sulfur and the background value of active phosphorus in sediments. The passivation/activation of phosphorus was mainly controlled by the oxidative adsorption/reductive dissolution of phosphorus by iron oxides and the activation of phosphorus induced by sulfate reduction and sulfide accumulation. Along the sampling sites, the average concentration of DGT-P varied greatly (0.075-0.80 mg·L-1), which was not related to salinity but closely related to redox conditions, that is, the deeper the oxidation zone, the lower the average concentration of DGT-P. The simulation results showed that the phosphorus resupply capacity from surface sediments to porewater was correlated with DGT-P concentration and redox conditions, that is, the oxidative environment was unconducive to the desorption and resupply of sediment phosphorus, whereas the coupling with iron and sulfur geochemistry in the reducing environment was conducive to the maintenance of high labile phosphorus concentration and the continuous release of phosphorus.

[Clinical Observation of Neutropenia Patients with Hematonosis Treated with Polymyxin B Sulfate].

OBJECTIVE: To observe the clinical efficacy and safety of polymyxin B sulfate in febrile neutropenia patients with hematonosis. METHODS: Clinical data of 50 patients in the department of hematology, Fujian Medical University Union Hospital from October 2019 to September 2020 were collected. All the patients developed febrile neutropenia after chemotherapy or hematopoietic stem cell transplantation. According to the results of drug susceptible test, polymyxin B sulfate was administrated mainly when the empirical antimicrobial treatments was poor and the pathogenic microbes test was positive. RESULTS: A total of 85 times of infection occurred in 50 patients. The infection sites were lung, blood flow, intestinal tract, oral cavity, perianal, soft tissue and nasal cavity. Gram negative bacteria was the main pathogenic microbe. After administration of polymyxin B sulfate when the etiology was confirmed, the total effective rate was 68%, especially the effective rate increased significantly after more than 7 days of polymyxin B sulfate treatment. Also, 24% and 8% of the patients were discharged automatically and died respectively. The effective rate of patients receiving carbapenem antibiotics changed to polymyxin B sulfate within 14 or 7 days was 80% and 70.6%, respectively, while the effective rate of patients who changed after 2 weeks was only 33.3%. The effective rate of patients receiving tigecycline changed to polymyxin B sulfate within 14 or 7 days was 80% and 66.7%, respectively. The incidence of adverse reactions of polymyxin B sulfate was low, most of which were mild, and only one patient occurred rhabdomyolysis. CONCLUSION: Polymyxin B sulfate has good clinical efficacy and safety in febrile neutropenia patients with hematonosis.

Effects of Different Pesticides on the Brewing of Wine Investigated by GC-MS-Based Metabolomics.

The application of pesticides is critical during the growth of high-quality grape for wine making. However, pesticide residues have significant influence on the wine flavor. In this study, gas chromatography-mass spectrometry (GC-MS) was performed and the obtained datasets were analyzed with multivariate statistical methods to investigate changes in flavor substances in wine during fermentation. The principal component analysis (PCA) score plot showed significant differences in the metabolites of wine treated with various pesticides. In trials using five pesticides (hexaconazole, difenoconazole, flutriafol, tebuconazole, and propiconazole), more than 86 metabolites were changed. Most of these metabolites were natural flavor compounds, like carbohydrates, amino acids, and short-chain fatty acids and their derivatives, which essentially define the appearance, aroma, flavor, and taste of the wine. Moreover, the five pesticides added to grape pulp exhibited different effects on the metabolic pathways, involving mainly alanine, aspartate and glutamate metabolism, butanoate metabolism, arginine, and proline metabolism. The results of this study will provide new insight into the potential impact of pesticide residues on the metabolites and sensory profile of wine during fermentation.

The optimized biocatalytic synthesis of (S)-methyl 2-chlorobutanoate by Acinetobacter sp. lipase.

Epilepsy is a chronic disease caused by sudden abnormal discharge of brain neurons, leading to transient brain dysfunction. Levetiracetam, developed by the UCB company in Belgium, is an effective drug for the treatment of epilepsy. (S)-Methyl 2-chlorobutanoate is an important chiral building block of levetiracetam, which has attracted a great deal of attention. In this study, a strain of lipase-produced Acinetobacter sp. zjutfet-1 was screened from soil samples. At optimized conditions for fermentation and biocatalysis, the bacterial lipase exhibited high catalytic activity for hydrolysis and stereoselectivity toward racemic methyl 2-chlorobutanoate. When the enzymatic reaction was carried out in 6% of racemic substrate, the enantiomeric excess (e.e.s ) reached more than 95%, with a yield of over 86%. Therefore, this lipase can efficiently resolve racemic methyl 2-chlorobutanoate and obtain (S)-methyl 2-chlorobutanoate, which presents great potential in the industrial production of levetiracetam.

Bright CsPbBr3 Perovskite Nanocrystals with Improved Stability by In-Situ Zn-Doping.

In this study, facile synthesis, characterization, and stability tests of highly luminescent Zn-doped CsPbBr3 perovskite nanocrystals (NCs) were demonstrated. The doping procedure was performed via partial replacement of PbBr2 with ZnBr2 in the precursor solution. Via Zn-doping, the photoluminescence quantum yield (PLQY) of the NCs was increased from 41.3% to 82.9%, with a blue-shifted peak at 503.7 nm and narrower spectral width of 18.7 nm which was consistent with the highly uniform size distribution of NCs observed from the TEM image. In the water-resistance stability test, the doped NCs exhibited an extended period-over four days until complete decomposition, under the harsh circumstances of hexane-ethanol-water mixing solution. The Zn-doped NC film maintained its 94% photoluminescence (PL) intensity after undergoing a heating/cooling cycle, surpassing the un-doped NC film with only 67% PL remaining. Based on our demonstrations, the in-situ Zn-doping procedure for the synthesis of CsPbBr3 NCs could be a promising strategy toward robust and PL-efficient nanomaterial to pave the way for realizing practical optoelectronic devices.

Bioinspired antifouling Fe-based amorphous coating via killing-resisting dual surface modifications.

Fe-based amorphous coatings with outstanding corrosion resistance are promise for marine applications. However, these coatings encounter a great challenge of biofouling in marine environments. Inspired by the unique micro-nano hierarchical structure of shark skin with excellent antifouling properties, in this paper, we construct a bioinspired Fe-based amorphous coating with killing-resisting dual-effect via proper surface modifications, i.e., the modification with micro-patterned nanostructured Cu2O fibers (killing effect), followed by the modification with superhydrophobic surface (resisting effect). As a result, the modified amorphous coating exhibits impressive antifouling properties, achieving 98.6% resistance to Nitzschia closterium f. minutissima, 87% resistance to Bovine serum albumin protein and 99.8% resistance to Pseudomonas aeruginosa, respectively. The remarkable antifouling performance is attributed to a synergistic antifouling mechanism from both resisting effect and killing effect, wherein the superhydrophobic surface provides a barrier to resist protein adsorption, while the patterned nanostructured Cu2O fibers supply Cu+ ions to kill bacterial cells. In addition, the modified amorphous coating also exhibits excellent mechanical robustness, which ensures the durability of the Fe-based amorphous coating in practical services. This work may promote the development of new durable metal-based coatings integrated with anti-fouling and anti-corrosion properties.

Heart rate-corrected QT interval: A novel diagnostic biomarker for diabetic peripheral neuropathy.

AIMS/INTRODUCTION: To explore the relationship between heart rate-corrected QT (QTc) interval and diabetic peripheral neuropathy (DPN), and whether QTc interval has diagnostic utility for DPN beyond nerve conduction velocity. MATERIALS AND METHODS: A total of 965 patients with diabetes, including 473 patients with DPN and 492 patients without DPN, underwent standard 12-lead electrocardiography and detailed assessments of peripheral neuropathy. RESULTS: Patients with DPN had longer QTc intervals than those without. Among participants, from the first to fourth quartile of QTc interval, the proportion of patients with DPN appreciably increased and the nerve conduction velocity obviously decreased (P for trend <0.001). The univariate and multivariate analyses showed that prolonged QTc interval was closely associated with increased risk of DPN (univariable odds ratio 1.112, 95% confidence interval 1.097-1.127, P < 0.001; multivariable odds ratio 1.118, 95% confidence interval 1.099-1.137, P < 0.001). Receiver operating characteristic analysis for the diagnosis of DPN showed a greater area under the curve for QTc interval of 0.894 than the median nerve motor conduction velocity of 0.691, median nerve sensory conduction velocity of 0.664 and peroneal nerve motor conduction velocity of 0.692. The optimal cut-off point of QTc interval for DPN was 428.5 ms with sensitivity of 0.715 and specificity of 0.920 (P < 0.001). The combination of QTc interval and nerve conduction testing increased the area under the curve for the diagnosis of DPN (from 0.736 to 0.916; P < 0.001). CONCLUSIONS: QTc interval with 428.5 ms has more reliable diagnostic utility for DPN than nerve conduction velocity, and prolonged QTc interval is closely associated with an increased risk of DPN.

[Expression and Clinical Significance of Heat Shock Protein 90 in Multiple Myeloma Patients].

OBJECTIVE: To investigate the expression of HSP90 in bone marrow samples of multiple myeloma (MM) patients and explore its clinical significance. METHODS: Maxvision immunohistochemistry technique was used to detect the protein expression level of HSP90 76 MM patients and 29 normal healthy donors. The clinical characteristics of the patients were collected, and the correlation between the HSP90 expression and the clinical characteristics was analyzed. RESULTS: The count of MM patients with positive HSP90 protein was significantly higher than that of normal healthy donor, and there were no significant correlation between HSP90 expression and age, sex, hemoglobin (Hb), creatinine (CREA), blood calcium, lactate dehydrogenase (LDH), bone marrow plasma cell proportion and MM subtypes (P>0.05), but HSP90 expression was correlated with ß2-microglobulin (ß2-MG) and ISS stage (P<0.05). The survival time was lower in MM patients with high expression HSP90 as compared with low expression HSP90 MM patients. CONCLUSION: HSP90 protein was over-expressed in MM patients, and was correlated with ß2-microglobulin, ISS stage and OS of MM patients.

Comparative Study of the Clinical Application of 2 Bleeding Grading Systems for Pregnant Women With Immune Thrombocytopenia.

Objective: To compare the clinical practicability of two bleeding grading systems (BGS) in pregnancy with Immune Thrombocytopenia (ITP). Methods: The clinical data of 154 cases were retrospectively analyzed with the 2016 version of the ITP Bleeding Scale (ITP-2016) and the ITP-specific bleeding assessment tool (ITP-BAT). The correlation between the two BGS and the relations among the platelet counts, gestational ages, and disease stages were respectively analyzed. Results: There is no significant difference between the two BGS in the patients' ages, nor between the newly diagnosed and the persistent group or the chronic group, while the difference between the persistent and the chronic group was significant (P = 0.001; P = 0.001). There is a negative correlation between the bleeding grade and platelet count (r = -0.436; r = -0.390), while the correlation between the two BGS was positive (r = 0.921). The proportions of identical scores provided by two different physicians using the two BGS were 94.8% and 93.5%. The difference before and after the treatment were significantly different (P = 0.013; P = 0.037). It takes less time to score with the ITP-2016 (P = 0.011). Conclusion: Both systems can be useful for disease evaluations, risk assessments and efficacy evaluations in Chinese pregnant women with ITP. The ITP-2016 takes less time and is more suitable for Chinese pregnant patients with ITP.

Cytogenetic abnormalities in patients with newly diagnosed multiple myeloma as a secondary primary malignancy: a retrospective study.

Objectives: Multiple myeloma (MM) often develops as a secondary primary malignancy (SPM). The retinoblastoma susceptibility gene (RB1) was the first tumour suppressor gene to be identified. We pooled and analyzed available data to compare the incidence of RB1 gene deletions and other cytogenetic abnormalities in patients with MM alone or as an SPM.Methods: We conducted a retrospective study of 475 patients. The experimental group comprised 18 patients with MM as an SPM, and the control group comprised 457 MM patients. We analyzed the baseline information in both groups, and used the odds ratio (OR), 95% confidence interval (CI), and forest plot to determine the incidence of SPMs with and without cytogenetic abnormalities.Results: The incidence of RB1 gene deletion was higher in the experimental group. There was no significant difference in other cytogenetic abnormalities.Conclusions: RB1 gene deletions appear to be associated with MM that develops as an SPM.

PiggyBac transposon system with polymeric gene carrier transfected into human T cells.

CAR-T cell-based immunotherapy has shown great promise in clinical trials for the treatment of hematological malignancies. The majority of these trials utilize retroviral and lentiviral vectors to introduce CAR transgene. In spite of its satisfactory efficiency, the concerns about the potential carcinogenicity and complicated synthesis procedure restrict widespread clinical applications of viral vectors. Recent studies show that transposon-based gene transfer is a safer and simpler non-viral approach for stable transgene expression. Here, we developed an in house made polymeric nanomicelles carrier for piggyBac (PB) transposon delivery to primary T lymphocytes. The properties, transfection efficiency and toxicity of this carrier was analyzed. Results indicated that nanomicelles produced in our study were stable and reduction-sensitive. These micelles can completely condense DNA and mediate transfection with efficiency of average 30.2% with high cell viability (> 80%). Furthermore, incorporating piggyBac transposase elements into polyplexes promoted persistent expression of the transgene (up to 55%). At the end of culture, CAR-T cells mainly exhibited memory phenotype and consisted of CD3+CD8+ T cells. The cytotoxicity of these CAR-T cells was average 17% at 20:1 ratio. In conclusion, polymeric nanomicelles provide a flexible and safe method for gene delivery to T lymphocytes.

TL1A modulates the severity of colitis by promoting Th9 differentiation and IL-9 secretion.

AIMS: TL1A was reported to contribute to the susceptibility to ulcerative colitis (UC). However, the molecular mechanisms of TL1A in UC development are poorly understood. We aimed to investigate the role of TL1A in colitis, and reveal the regulatory mechanism of TL1A in chronic colitis development. MAIN METHODS: Wild-type mice and transgenic mice with overexpressing TL1A in lymphocytes were used to construct chronic DSS colitis models. To investigate the molecular mechanism in vitro, CD4+ T cells were sorted from spleens and mesenteric lymph node cells to induce Th9 cells. Biopsy specimens from ulcerative colitis patients were collected for in vivo validation. KEY FINDINGS: The elevated TL1A expression in chronic DSS colitis models exacerbated intestinal inflammation. The differentiation of Th9 cells, IL-9 secretion and production of TGF-ß, IL-4 and PU.1 was significantly enhanced in transgenic mice with TL1A overexpression. In vitro results showed that TL1A enhanced the Th9 cells, IL-9 and PU.1 production, while TL1A antibodies inhibited their production. In human translational studies, patients with ulcerative colitis with elevated TL1A expression also exhibited more serious inflammation with higher levels of Th9 cells, IL-9 and PU.1 expression. SIGNIFICANCE: We presented a possible mechanism of TL1A in UC development that TL1A may promote the differentiation of Th9 cells and enhanced IL-9 secretion by up-regulating the expression of TGF-ß, IL-4 and PU.1, which provided a novel perspective to study the UC pathogenesis, and indicated that targeting of TL1A signal pathway may by a likely strategy for the treatment of chronic colitis.

SENP2 exerts an anti­tumor effect on chronic lymphocytic leukemia cells through the inhibition of the Notch and NF­κB signaling pathways.

Chronic lymphocytic leukemia (CLL) is one of the most often diagnosed hematological malignant tumors in the Western world and a type of inert B­cell lymphoma that commonly attacks the elderly. Small ubiquitin related modifier (SUMO)­specific protease 2 (SENP2) can act as a suppressor in various types of cancer by regulating the stability of ß­catenin to affect the Notch signaling pathway; however, it has a low expression level in CLL cells. In this study, we firstly used western blot analysis and RT­qPCR to detect the protein and mRNA expression levels of SENP2 in the peripheral blood of patients with CLL and healthy volunteers. Secondly, we overexpressed or knocked down the expression of SENP2 in CLL cells and then determined the cell invasive and chemotactic ability in a Transwell assay and chemotaxis assay. We examined the sensitivity of the cells to cytarabine and dexamethasone via a CCK­8 assay and determined the cell apoptotic condition and the expression of the Notch signaling pathway using flow cytometry and western blot analysis. The results demonstrated that the patients with CLL had relatively low expression levels of SENP2. The overexpression of SENP2 in the CLL cells decreased their invasive and proliferative ability, as well as their chemotactic response and enhanced their sensitivity to cytarabine and dexamethasone, while it promoted cell apoptosis. The silencing of SENP2 in the CLL cells generally produced the opposite results. We thus hypothesized that the overexpression of SENP2 downregulated ß­catenin expression, thus inhibiting the Notch signaling pathway in CLL cells. Moreover, the nuclear factor (NF)­κB signaling pathway was also regulated by the overexpression of SENP2. On the whole, the findings of this study indicate tha SENP2 can act as a tumor suppressor in CLL cells, and may thus prove to be a novel target for CLL treatment in clinical practice.

Comparison of the life-history parameters and competition outcome with Moina macrocopa between two morphs of Brachionus forficula.

In rotifers, the costs of morphological defenses, especially the development of long spines, have been investigated for several decades. However, the obtained results were inconsistent and the underlying reasons were complicated. Investigations on more species might be helpful to find out the reasons. In the present study, Brachionus forficula was selected as the model organism. The differences in developmental durations, life-table demography, starvation resistant time and the competitive ability with Moina macrocopa were compared between B. forficula with long (LPS) and short (SPS) posterior spines. The results showed that LPS showed relatively longer durations of juvenile stage at 1.0 × 106, 2.0 × 106 and 4.0 × 106 cells/ml Scenedesmus obliquus, and longer embryo stage at 2.0 × 106 cells/ml S. obliquus than SPS. The intrinsic rate of population increase and net reproduction rate were lower in LPS than SPS, suggesting the energy input to reproduction decreased. The starvation resistant time was also reduced in LPS, in comparison to SPS, further supporting that LPS consumed more energy, which might be directed to the development of long spines. All these results revealed that LPS spent more energy for individual growth than SPS, which might be used to develop long spines. Moreover, the maximum population density and population growth rate of LPS were always lower than those of SPS, suggesting that LPS might have a weaker competition ability with M. macrocope than SPS.