Impact of COVID-19 infection experience on mental health status of intensive care unit patients' family members: a real-world study.

PURPOSE: Family members of patients hospitalized in intensive care unit (ICU) are susceptible to adverse psychological outcomes. However, there is a paucity of studies specifically examining the mental health symptoms in ICU patients' family members with a prior history of coronavirus disease 2019 (COVID-19) infection. AIM: This study aimed to investigate mental health status and its influencing factors of ICU patients' family members with previous COVID-19 infection experience in China. DESIGN: Nationwide, cross-sectional cohort of consecutive participants of family members of ICU patients from 10 provinces randomly selected in mainland China conducted between October 2022 and May 2023. METHODS: The basic information scale, Self-rating depression scale, Self-rating Anxiety Scale, Impact of Event Scale-Revised, Pittsburgh sleep quality index, Perceived Stress Scale, Connor-Davidson resilience scale, Simplified Coping Style Questionnaire were employed to explore mental health status among participants. RESULTS: A total of 463 participants, comprising 156 individuals in Covid-19 family member cohort (infection group) and 307 individuals in control family member cohort (control group), met inclusion criteria. The infection group exhibited significantly higher incidence of composite mental health symptoms compared to control group (P = 0.017). Multivariable logistic regression analysis revealed that being female, engaging in physical/mental labor, residing in rural areas, and having children were identified as risk factors for the development of depression, anxiety, and post-traumatic stress disorder symptoms, while medical history of surgery was protective factor. A predictive model demonstrated a favorable discriminative ability and excellent calibration. CONCLUSION: COVID-19 infection experience regarded as new traumatic stressors worsen mental health status of ICU patients' family members.

[Endoscopic treatment of infectious necrosis in severe acute pancreatitis].

Severe acute pancreatitis (SAP) is one of the most common acute and critical diseases. SAP is often accompanied by necrosis of the pancreas and surrounding tissues.When necrosis is co-infected, it often means high mortality. With the development of endoscopic technology, endoscopic intervention in the treatment of necrotizing pancreatitis has achieved good results, which has the advantages of minimal-invasiveness, effectiveness, and safety, and could significantly improve the prognosis of patients with SAP. This article aims to review the research progress of endoscopic treatment of necrotizing pancreatitis.

Composition-dependent effects of oxygen on atomic structure and mechanical properties of metallic glasses.

Although minor alloying in metallic glasses (MGs) has been extensively investigated, the effect of O doping is still a debatable topic. In the present study, the atomic-level structures and mechanical properties of Zr-based MGs doped with different O contents have been analyzed using ab initio molecular dynamics simulations. It is revealed that O atoms prefer to bond to Zr atoms due to their low mixing enthalpy, and that O atoms degrade the properties of Zr-lean MGs but hardly affect the properties of Zr-rich MGs, with results suggesting a compositional dependence of O doping. For Zr-lean MGs, the fraction of full icosahedra, size of the medium-range-order clusters, Young's modulus and shear modulus decrease sharply with O content, while accompanied by a sharp increase of the non-Frank-Kasper polyhedra, and the ratio of bulk modulus to shear modulus and Poisson's ratio, indicating decreased strength and improved plasticity. For Zr-rich MGs, however, the above-mentioned structural and mechanical features experience little change or only change slightly after O doping, showing low oxygen sensitivity. It is shown that the high Zr content weakens the effect of Zr-O bonding to some extent. The present study not only sheds light on the atomic-level structures of O-doped MGs, which may provide guidelines for designing MGs with low-grade materials, but also helps to explain the previous conflicting results based on the composition-dependence effect.

Correlation analysis of ADAMTS-4, VCAM-1, and TAK1 expression in cartilage tissue from spine tuberculosis.

A disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS-4) can effectively degrade articular cartilage matrix proteoglycan and damage the intervertebral disc of spinal tuberculosis patients, resulting in deterioration of the physical properties of articular cartilage. Transforming growth factor ß activated kinase 1 (TAK1) is similar to vascular cell adhesion molecule 1 (VCAM-1) and closely related to a variety of pathophysiological processes. This study intended to explore the expression of ADAMTS-4, VCAM-1, and TAK1 in cartilage tissue obtained from spinal tuberculosis patients and their inter-relationships, aiming to provide new treatment approaches for spinal tuberculosis. Patients with spinal tuberculosis (N = 60) from the department of orthopedics and patients with traumatic spinal fracture (N = 60, controls) were recruited for the study. ADAMTS-4, VCAM-1, and TAK1 expression was detected by immunohistochemistry. SPSS 19.0 software was used for data processing and analysis. The score values of ADAMTS-4, TAK1, and VCAM-1 were 1.45 ± 0.10, 1.33 ± 0.09, and 1.54 ± 0.11, respectively, which were significantly higher than those in normal controls (P < 0.05). ADAMTS-4 showed positive correlation with VCAM-1 and TAK1. ADAMTS-4, TAK1, and VCAM-1 expressions increased in spinal tuberculosis patients. They could provide clinical reference for spinal tuberculosis diagnosis and new treatment strategies can be devised by focusing on their positive correlation.

Efficient androst-1,4-diene-3,17-dione production by co-expressing 3-ketosteroid-Δ1 -dehydrogenase and catalase in Bacillus subtilis.

AIMS: 3-ketosteroid-Δ1 -dehydrogenase (KSDD), a flavin adenine dinucleotide (FAD)-dependent enzyme involved in sterol metabolism, specifically catalyses the conversion of androst-4-ene-3,17-dione (AD) to androst-1,4-diene-3,17-dione (ADD). However, the low KSDD activity and the toxic effects of hydrogen peroxide (H2 O2 ) generated during the biotransformation of AD to ADD with FAD regeneration hinder its application on AD conversion. The aim of this work was to improve KSDD activity and eliminate the toxic effects of the generated H2 O2 to enhance ADD production. METHODS AND RESULTS: The ksdd gene obtained from Mycobacterium neoaurum JC-12 was codon-optimized to increase its expression level in Bacillus subtilis, and the KSDD activity reached 12·3 U mg-1 , which was sevenfold of that of codon-unoptimized gene. To improve AD conversion, catalase was co-expressed with KSDD in B. subtilis 168/pMA5-ksddopt -katA to eliminate the toxic effects of H2 O2 generated during AD conversion. Finally, under optimized bioconversion conditions, fed-batch strategy was carried out and the ADD yield improved to 8·76 g l-1 . CONCLUSIONS: This work demonstrates the potential to improve enzyme activity by codon-optimization and eliminate the toxic effects of H2 O2 by co-expressing catalase. SIGNIFICANCE AND IMPACT OF THE STUDY: This study showed the highest ADD productivity ever reported and provides a promising strain for efficient ADD production in the pharmaceutical industry.

Cyclic Deformation in Metallic Glasses.

Despite the utmost importance and decades of experimental studies on fatigue in metallic glasses (MGs), there has been so far little or no atomic-level understanding of the mechanisms involved. Here we perform molecular dynamics simulations of tension-compression fatigue in Cu50Zr50 MGs under strain-controlled cyclic loading. It is shown that the shear band (SB) initiation under cyclic loading is distinctly different from that under monotonic loading. Under cyclic loading, SB initiation takes place when aggregates of shear transformation zones (STZs) accumulating at the MG surface reach a critical size comparable to the SB width, and the accumulation of STZs follows a power law with rate depending on the applied strain. It is further shown that almost the entire fatigue life of nanoscale MGs under low cycle fatigue is spent in the SB-initiation stage, similar to that of crystalline materials. Furthermore, a qualitative investigation of the effect of cycling frequency on the fatigue behavior of MGs suggests that higher cycling frequency leads to more cycles to failure. The present study sheds light on the fundamental fatigue mechanisms of MGs that could be useful in developing strategies for their engineering applications.

Strong and superplastic nanoglass.

The strength-ductility tradeoff has been a common long-standing dilemma in materials science. For example, superplasticity with a tradeoff in strength has been reported for Cu50Zr50 nanoglass (NG) with grain sizes below 5 nm. Here we report an improvement in strength without sacrificing superplasticity in Cu50Zr50 NG by using a bimodal grain size distribution. Our results reveal that large grains impart high strength, which is in striking contrast to the physical origin of the improvement in strength reported in the traditional nanostructured metals/alloys. Furthermore, the mechanical properties of NG with a bimodal nanostructure depend critically upon the fraction of large grains. By increasing the fraction of the large grains, a transition from superplastic flow to failure by shear banding is clearly observed. We expect that these results will be useful in the development of a novel strong and superplastic NG.

Necking and notch strengthening in metallic glass with symmetric sharp-and-deep notches.

Notched metallic glasses (MGs) have received much attention recently due to their intriguing mechanical properties compared to their unnotched counterparts, but so far no fundamental understanding of the correlation between failure behavior and notch depth/sharpness exists. Using molecular dynamics simulations, we report necking and large notch strengthening in MGs with symmetric sharp-and-deep notches. Our work reveals that the failure mode and strength of notched MGs are strongly dependent on the notch depth and notch sharpness. By increasing the notch depth and the notch sharpness, we observe a failure mode transition from shear banding to necking, and also a large notch strengthening. This necking is found to be caused by the combined effects of large stress gradient at the notch roots and the impingement and subsequent arrest of shear bands emanating from the notch roots. The present study not only shows the failure mode transition and the large notch strengthening in notched MGs, but also provides significant insights into the deformation and failure mechanisms of notched MGs that may offer new strategies for the design and engineering of MGs.

High expression of kinesin light chain-2, a novel target of miR-125b, is associated with poor clinical outcome of elderly non-small-cell lung cancer patients.

BACKGROUND: MiR-125b has critical role in non-small-cell lung cancer (NSCLC) cell migration, and its target genes have not been elucidated. Kinesin-1 light chain (KLC)-2 was predicted as one of miR-125b's targets by bioinformatics analysis. This study is to identify the function of KLC2 and its interaction with miR-125b in NSCLC. METHODS: Kinesin-1 light chain-2 protein expression and its clinical relevance were analysed in 140 matched NSCLC and adjacent non-neoplastic lung tissues. Both KLC2 gain- and loss-of-function analyses were performed in NSCLC cell lines by transient transfection. The direct interaction between KLC2 and miR-125b was confirmed by a luciferase reporter assay and a transient co-transfection assay as well as an analysis of eight matched clinical samples. RESULTS: KLC2 protein was upregulated in NSCLC cell lines and tissues, and was an independent predictor of poor prognosis for elderly NSCLC patients. Kinesin-1 light chain-2 remarkably enhanced the invasive and migratory ability of NSCLC cells. MiR-125b inhibited KLC2 3'-untranslated region luciferase activity and protein expression, and inversely correlated with KLC2 expression in clinical samples. Kinesin-1 light chain-2 almost completely reversed miR-125b-induced inhibition on migration and invasion. CONCLUSIONS: Kinesin-1 light chain-2 protein overexpression predicts poor survival in elderly NSCLC patients. Kinesin-1 light chain-2 acts as a proto-oncogene and a functional target of miR-125b in NSCLC cells.

Establishment and characterization of an ovarian cell line from half-smooth tongue sole Cynoglossus semilaevis.

A new ovarian cell line, CSO, was established from half-smooth tongue sole Cynoglossus semilaevis. Primary culture of CSO cells was initiated from digestion of ovarian tissues pieces by trypsin solution and cultured at 24° C in Dulbecco's modified Eagle's medium-F12 medium (DMEM-F12, 1:1) (pH 7·0), supplemented with 20% foetal bovine serum, basic fibroblast growth factor (bFGF), epidermal growth factor (EGF), insulin-like growth factor-I (IGF-I) and human chorionic gonadotropin (HCG). The cultured CSO cells, fibroblastic in morphology, proliferated to 100% confluency 3 days later and had been subcultured to passage 80. Chromosome analyses indicated that the CSO cells exhibited chromosomal aneuploidy with a modal chromosome number of 42 that displayed the normal diploid karyotype of C. semilaevis [2n = 42 t, fundamental number (NF ) = 42]. Reverse transcription polymerase chain reaction revealed that CSO cells could express ovarian somatic cell functional genes p450armo, foxl2 and sox9a but not ovary germ cell marker gene vasa and male-specific gene dmrt1. Transfection experiment demonstrated that CSO cells transfected with pEGFP-N3 plasmid could express green fluorescence protein (GFP) with higher transfection efficiency. The CSO cell line might serve as a valuable tool for studies on the mechanism of sex determination and oogenesis of ovary in flatfish.

On the failure load and mechanism of polycrystalline graphene by nanoindentation.

Nanoindentation has been recently used to measure the mechanical properties of polycrystalline graphene. However, the measured failure loads are found to be scattered widely and vary from lab to lab. We perform molecular dynamics simulations of nanoindentation on polycrystalline graphene at different sites including grain center, grain boundary (GB), GB triple junction, and holes. Depending on the relative position between the indenter tip and defects, significant scattering in failure load is observed. This scattering is found to arise from a combination of the non-uniform stress state, varied and weakened strengths of different defects, and the relative location between the indenter tip and the defects in polycrystalline graphene. Consequently, the failure behavior of polycrystalline graphene by nanoindentation is critically dependent on the indentation site, and is thus distinct from uniaxial tensile loading. Our work highlights the importance of the interaction between the indentation tip and defects, and the need to explicitly consider the defect characteristics at and near the indentation site in polycrystalline graphene during nanoindentation.

Inverse pseudo Hall-Petch relation in polycrystalline graphene.

Understanding the grain size-dependent failure behavior of polycrystalline graphene is important for its applications both structurally and functionally. Here we perform molecular dynamics simulations to study the failure behavior of polycrystalline graphene by varying both grain size and distribution. We show that polycrystalline graphene fails in a brittle mode and grain boundary junctions serve as the crack nucleation sites. We also show that its breaking strength and average grain size follow an inverse pseudo Hall-Petch relation, in agreement with experimental measurements. Further, we find that this inverse pseudo Hall-Petch relation can be naturally rationalized by the weakest-link model, which describes the failure behavior of brittle materials. Our present work reveals insights into controlling the mechanical properties of polycrystalline graphene and provides guidelines for the applications of polycrystalline graphene in flexible electronics and nano-electronic-mechanical devices.

Molecular dynamics simulations on the frictional behavior of a perfluoropolyether film sandwiched between diamond-like-carbon coatings.

We perform molecular dynamics simulations to investigate the nanoscale frictional behavior of a perfluoropolyether (PFPE) film sandwiched between two diamond-like-carbon (DLC) coatings. We show that the PFPE films behave like a solid and can perform either a motion-station movement or a continuous motion with fluctuating velocities. The former movement is caused by the alternating stick and slip at the two individual interfaces, while the latter is due to the dynamic sliding motions simultaneously occurring at both interfaces. We reveal that these motion characteristics are governed by the competition between the two interfacial adhesion energies, which are strongly affected by the thermal vibrations and interface roughness fluctuations. We also find that the Amonton's law modified by incorporating the adhesion effect can be used to describe the mean friction traction vs normal pressure relation, but large fluctuations are present at low contact pressures. The magnitude of atomic level friction forces at the interface is found to be highly nonuniform. The directions of atomic level friction forces can even be opposite. With increasing the normal pressure, the nonuniformity of atomic level friction forces decreases first and then increases again. This change can be explained by the concurrent effects from the large difference in material stiffness and the changes in surface roughness under normal pressure. The present work reveals interesting insights into the sliding mechanisms in sandwiched structures and provides useful guidelines for the design of nanoscale lubricant systems.

Development and characterization of 60 novel EST-SSR markers in half-smooth tongue sole Cynoglossus semilaevis.

Sixty novel simple sequence repeat (SSR) markers were developed from expressed sequence tags (EST) of half-smooth tongue sole Cynoglossus semilaevis exploited in the laboratory. The number of alleles, observed and expected heterozygosity per locus ranged from two to 16, from 0·0833 to 1·0000 and from 0·0816 to 0·913, respectively. Of these SSRs, 20 had significant homology to known genes by BLASTx (basic local alignment search tool x) search. For cross-species amplification, there are 53 positive amplifications in Japanese flounder Paralichthys olivaceus with 12 polymorphic loci and 51 positive amplifications in Senegalese sole Solea senegalensis with 11 polymorphic loci. These new EST-SSR markers will be useful for genetic studies and genome mapping of C. semilaevis and its closely related fishes.

Development and characterization of a new marine fish cell line from turbot (Scophthalmus maximus).

A new marine fish cell line, TK, derived from turbot (Scophthalmus maximus) kidney, was established by the method of trypsin digestion and subcultured for more than 50 passages over a period of 300 days. The TK cells were maintained in Minimum Essential Medium Eagle (MEM) supplemented with HEPES, antibiotics, fetal bovine serum (FBS), 2-Mercaptoethanol (2-Me), and basic fibroblast growth factor (bFGF). The suitable growth temperature for TK cells was 24°C, and microscopically, TK cells were composed of fibroblast-like cells. Chromosome analysis revealed that the TK cell line has a normal diploid karyotype with 2n=44. Two fish viruses LCDV-C (lymphocystis disease virus from China) and TRBIV (turbot reddish body iridovirus) were used to determine the virus susceptibility of TK cell line. The TK cell line was found to be susceptible to TRBIV, and the infection was confirmed by cytopathic effect (CPE) and transmission electron microscopy, which detected the viral particles in the cytoplasm of virus-infected cells. Finally, significant green fluorescent signals were observed when the TK cells were transfected with pEGFP-N3 vector, indicating its potential utility for fish virus study and genetic manipulation.

Establishment, characterization of a new cell line from heart of half smooth tongue sole (Cynoglossus semilaevis).

A new cell line was established from the heart of a cultured marine fish, half smooth tongue sole (Cynoglossus semilaevis), designated as CSH (Cynoglossus semilaevis heart cell line). The CSH cells grow over 400 days in minimum essential medium (MEM) supplemented with 10% fetal bovine serum (FBS) and 2 ng/ml basic fibroblast growth factor (bFGF). The suitable temperature for the cell growth was 24-30°C with the optimum growth at 24°C and a reduced growth at 12 and 30°C. FBS and bFGF concentration were the two important components for CSH cells proliferation. Twenty percent FBS in the medium was found to be the optimum concentration and bFGF promoted the growth of CSH cells. The double time of the cells at 24°C was determined to 73.39 h. Chromosome analysis revealed that 44% of the cells maintained a normal diploid chromosome number (2n=42) in the CSH cells at Passage 58. The fluorescent signals were observed in CSH after the cells were transfected with green fluorescent protein (GFP) reporter plasmids. CSH cells showed the cytopathic effect (CPE) after infection with lymphosystis disease virus (LCDV). Moreover, the LCDV particles can be observed in the cytoplasm of virus-infected cells by electron microscopy, and a segment of MCP gene for major capsid protein of LCDV was found by PCR amplification DNA of virus-infected cells.

Generation and analysis of 10 000 ESTs from the half-smooth tongue sole Cynoglossus semilaevis and identification of microsatellite and SNP markers.

Three normalized cDNA libraries were constructed, two of which were constructed from reproductive tissues ovary and testis, and the other one from pooled immune tissues including head kidney, intestine, liver and spleen. A total of 10 542 clones were sequenced generating 10 128 expressed sequence tags (ESTs). Cluster analysis indicated a total of 5808 unique sequences including 1712 contigs and 4096 singletons. A total of 4249 (73%) of the unique ESTs had significant hits to the non-redundant protein database, 2253 of which were annotated using Gene Ontology (GO) terms. A total of 311 microsatellites (with 246 having sufficient flanking sequences for primer design) and 6294 putative SNPs were identified. These genome resources provide the material basis for future microarray development, marker validation and genetic linkage and QTL analysis.

Major histocompatibility complex class IIB allele polymorphism and its association with resistance/susceptibility to Vibrio anguillarum in Japanese flounder (Paralichthys olivaceus).

The full length of major histocompatibility complex (MHC) class IIB cDNA was cloned from a Chinese population of Paralichthys olivaceus by homology cloning and rapid amplification of cDNA ends-polymerase chain reaction (RACE-PCR). The MHC IIB genomic sequence is 1,864 bp long and consists of 34-bp 5'UTR, 741-bp open reading frame, 407-bp 3'UTR, 96-bp intron1, 392-bp intron2, 85-bp intron3, and 109-bp intron4. Phylogenetic analysis showed that the putative MHC class IIB amino acid of the Chinese P. olivaceus shared 28.3% to 85.4% identity with that of the reported MHC class IIB in other species. A significant association between MHC IIB polymorphism and disease resistance/susceptibility was found in Chinese P. olivaceus. Thirteen different MHC IIB alleles were identified among 411 clones from 84 individuals. Among the 280 (268) nucleotides, 32 (11.4%) nucleotide positions were variable. Most alleles such as alleles a, b, c, d, e, f, j, k, i, m were commonly found in both resistant and susceptible stock. Via chi2 test, allele d was significantly more prevalent in individuals from susceptible stock than from resistant stock, and their percentages were 23.80% and 7.14%, respectively. In addition, allele g occurred in 9 and allele h in 4 of 42 resistant individuals that were not present in the susceptible stock; their percentages were 21.4% and 9.52%, respectively. Although allele l was found only in 8 individuals from the susceptible stock, its percentage is 19.05%.