Hollow Zeolite Nanoreactor with Double Shells for Methanol Aromatization: Explicit Recognition on Catalytic Function of Inverse Elemental Zone and Shell-Cavity.

Core@shell catalyst composited of dual aluminosilicate zeolite can effectively regulate the distribution of acid sites to control hydrocarbon conversion process for the stable formation of target product. However, the diffusion restriction reduces the accessibility of inner active sites and affects synergy between core and shell. Herein, hollow ZSM-5 zeolite nanoreactor with inverse aluminum distribution and double shells are prepared and employed for methanol aromatization. It is demonstrated that the intershell cavity alleviated the steric hindrance from zeolites channel and provided more paths and pore entrance for guest molecule. Correspondingly, olefin intermediates generated from methanol over the external shell are easier to adsorb at internal acid sites for further reactions. Importantly, the diffusion of generated aromatic macromolecules to the external surface is also promoted, which slows down the formation of internal coke, and ensures the use of internal acid sites for aromatization. The aromatics selectivity of the nanoreactor remained at 8% after 154 h, while that of solid core@shell catalyst decreased to 2% after 75 h. This finding promises broader insight to improve internal active site utilization of core@shell catalyst at the diffusion level and can be great aid in the flexible design of multifunctional nanoreactors to enhance the relay efficiency.

Speciation analysis and toxicity evaluation of arsenolipids-an overview focusing on sea food.

Arsenic, which can be divided into inorganic and organic arsenic, is a toxic metalloid that has been identified as a human carcinogen. A common source of arsenic exposure in seafood is arsenolipid, which is a complex structure of lipid-soluble organic arsenic compounds. At present, the known arsenolipid species mainly include arsenic-containing fatty acids (AsFAs), arsenic-containing hydrocarbons (AsHCs), arsenic glycophospholipids (AsPLs), and cationic trimethyl fatty alcohols (TMAsFOHs). Furthermore, the toxicity between different species is unique. However, the mechanism underlying arsenolipid toxicity and anabolism remain unclear, as arsenolipids exhibit a complex structure, are present at low quantities, and are difficult to extract and detect. Therefore, the objective of this overview is to summarize the latest research progress on methods to evaluate the toxicity and analyze the main speciation of arsenolipids in seafood. In addition, novel insights are provided to further elucidate the speciation, toxicity, and anabolism of arsenolipids and assess the risks on human health.

Cell damage repair mechanism in a desert green algae Chlorella sp. against UV-B radiation.

The protective ozone layer is continually depleting owing to an increase in the levels of solar UV-B radiation, which has harmful effects on organisms. Algae in desert soil can resist UV-B radiation, but most research on the radiation resistance of desert algae has focused on cyanobacteria. In this study, we found that desert green algae, Chlorella sp., could maintain high photosynthetic activity under UV-B stress. To examine the tolerance mechanism of the desert green algae photosystem, we observed the physiological and transcriptome-level responses of Chlorella sp. to high doses of UV-B radiation. The results showed that the reactive oxygen species (ROS) content first increased and then decreased, while the malondialdehyde (MDA) content revealed no notable lipid peroxidation during the UV-B exposure period. These results suggested that Chlorella sp. may have strong system characteristics for scavenging ROS. The antioxidant enzyme system showed efficient alternate coordination, which exhibited a protective effect against enhanced UV-B radiation. DNA damage and the chlorophyll and soluble protein contents had no significant changes in the early irradiation stage; UV-B radiation did not induce extracellular polysaccharides (EPS) synthesis. Transcriptomic data revealed that a strong photosynthetic system, efficient DNA repair, and changes in the expression of genes encoding ribosomal protein (which aid in protein synthesis and improve resistance) are responsible for the high UV-B tolerance characteristics of Chlorella sp. In contrast, EPS synthesis was not the main pathway for UV-B resistance. Our results revealed the potential cell damage repair mechanisms within Chlorella sp. that were associated with high intensity UV-B stress, thereby providing insights into the underlying regulatory adaptations of desert green algae.

Immunopathogenesis of Coronavirus-Induced Acute Respiratory Distress Syndrome (ARDS): Potential Infection-Associated Hemophagocytic Lymphohistiocytosis.

The outbreak of coronavirus disease 2019 (COVID-19) in December 2019 in Wuhan, China, introduced the third highly pathogenic coronavirus into humans in the 21st century. Scientific advance after the severe acute respiratory syndrome coronavirus (SARS-CoV) epidemic and Middle East respiratory syndrome coronavirus (MERS-CoV) emergence enabled clinicians to understand the epidemiology and pathophysiology of SARS-CoV-2. In this review, we summarize and discuss the epidemiology, clinical features, and virology of and host immune responses to SARS-CoV, MERS-CoV, and SARS-CoV-2 and the pathogenesis of coronavirus-induced acute respiratory distress syndrome (ARDS). We especially highlight that highly pathogenic coronaviruses might cause infection-associated hemophagocytic lymphohistiocytosis, which is involved in the immunopathogenesis of human coronavirus-induced ARDS, and also discuss the potential implication of hemophagocytic lymphohistiocytosis therapeutics for combating severe coronavirus infection.

BATF2 balances the T cell-mediated immune response of CADM with an anti-MDA5 autoantibody.

OBJECTIVES: Clinically amyopathic dermatomyositis (CADM) is a subtype of dermatomyositis (DM) characterized by low-grade or absent muscle inflammation but frequent and rapidly progressive interstitial lung disease (RP-ILD) and skin ulcers with anti-melanoma differentiation-associated gene 5 (anti-MDA5) autoantibodies. Basic leucine zipper transcription factor ATF-like 2 (BATF2) is thought to function as an inhibitor of tumours and inflammation. Here, we aimed to investigate the roles of BATF2 in Th cell differentiation of CADM with an anti-MDA5 autoantibody (anti-MDA5+ CADM). METHODS: Naive CD4+ T cells from human peripheral blood mononuclear cells (PBMCs) of healthy controls (HCs) were isolated and then cultured with IL-12, TGF-ß or TGF-ß plus IL-6 following anti-CD3 and anti-CD28 stimulations. The expression of BATF2 was measured by real-time PCR. The percentages of Th1, Th17 and Treg CD4+ T cells were detected by flow cytometry. BATF2 knockdown of CD4+ T cells was performed using small interfering RNAs (siRNAs). RESULTS: The expression of BATF2 in PBMCs was higher in anti-MDA5+ CADM patients than in healthy controls. The BATF2 mRNA expression was increased under Th1 and Treg polarization but decreased under Th17 polarization. Th17 cell activation-associated genes were possibly increased while Th1 and Treg cell differentiation-associated genes were inhibited by posttranscriptional gene silencing of BATF2 in CD4+ T cells. CONCLUSIONS: BATF2 promoted Th1 and Treg cell differentiation but suppressed Th17 cell activation in anti-MDA5+ CADM.

The TGF-ß/miR-31/CEACAM1-S axis inhibits CD4+ CD25+ Treg differentiation in systemic lupus erythematosus.

Defects causing concomitant loss of CD25 expression in regulatory T cells (Tregs) have been identified in systemic lupus erythematosus (SLE). However, the cause of this deficiency is not fully understood. Carcinoembryonic antigen related cell adhesion molecule 1 (CEACAM1), an immune co-receptor, contributes to general T-cell function and activation. Our previous study revealed that CEACAM1 expression was upregulated in peripheral blood mononuclear cells (PBMCs) from patients with SLE. However, its role remains unclear. Herein, we confirmed CEACAM1, especially CEACAM1-S, was upregulated in PBMCs from patients with SLE. CEACAM1-S over-expression inhibits CD4+ CD25+ Treg differentiation, whereas knockdown of CEACAM1 had the opposite effect in vitro. CEACAM1-S is the target of miR-31. MiR-31 mimic inhibits CEACAM1 expression and enhances CD4+ CD25+ Treg differentiation, which was reversed by CEACAM1-S over-expression. Moreover, the circulating TGF-ß level was upregulated in SLE patients and TGF-ß reduced miR-31 expression via enhancing NF-κB activity. Importantly, CEACAM1 and TGF-ß mRNA levels were downregulated, while the miR-31 level and the abundance of CD4+ CD25+ Tregs were increased in inactive patients compared with that in patients with active SLE. In addition, CEACAM1-S expression was positively correlated with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, while CD4+ CD25+ Treg abundance and miR-31 level were negatively correlated with the SLEDAI score. In conclusion, reduced activity of miR-31 by TGF-ß, via the inhibition of NF-ᴋB, acted to inhibit the differentiation of CD4+ CD25+ Tregs by directly targeting CEACAM1-S and to promote autoimmunity.

RPC4046, a Monoclonal Antibody Against IL13, Reduces Histologic and Endoscopic Activity in Patients With Eosinophilic Esophagitis.

BACKGROUND & AIMS: Eosinophilic esophagitis (EoE) is a chronic, esophageal, type 2 inflammatory response associated with increased serum levels of interleukin 13 (IL13), which might contribute to its pathogenesis. RPC4046, a recombinant humanized monoclonal antibody against IL13, prevents its binding to the receptor subunits IL13RA1 and IL13RA2. We performed a phase 2 trial to evaluate the efficacy and safety of RPC4046 in patients with EoE. METHODS: We performed a multicenter, double-blind trial of 99 adults with active EoE randomly assigned (1:1:1) to groups given RPC4046 (180 or 360 mg) or placebo once weekly for 16 weeks, from September 2014 through December 2015. Patients were seen at day 1 (baseline) and weeks 2, 4, 8, 12, and 16. They underwent esophagogastroduodenoscopy and biopsies were collected at baseline and week 16. Patients completed a daily dysphagia symptom diary through week 16 and patient-reported outcome data were collected. The primary outcome was change in mean esophageal eosinophil count in the 5 high-power fields (hpfs) with the highest level of inflammation. RESULTS: At week 16, mean changes in esophageal eosinophil count per hpf were a reduction of 94.8 ± 67.3 in patients who received 180 mg RPC4046 (P < .0001) and a reduction of 99.9 ± 79.5 in patients who received 360 mg RPC4046 (P < .0001) compared with a reduction of 4.4 ± 59.9 in patients who received placebo. The 360-mg RPC4046 group, compared with the placebo group, showed significant reductions in validated endoscopic severity score at all esophageal locations (P < .0001), validated histologic grade and stage scores (both P < .0001), and clinician's global assessment of disease severity (P = .0352); they had a numerical reduction in scores from the dysphagia symptom diary (P = .0733). Significant reductions in esophageal eosinophil counts and histologic and endoscopic features were observed in patients with steroid-refractory EoE who received RPC4046. The most common adverse events were headache and upper respiratory tract infection. CONCLUSIONS: In a phase 2 trial of patients with EoE, we found RPC4046 (a monoclonal antibody against IL13) to reduce histologic and endoscopic features compared with placebo. RPC4046 was well tolerated. ClinicalTrials.gov no: NCT02098473.

Space-Time Block Coded Cooperative MIMO Systems.

The main objective of a Cooperative Multiple-Input Multiple-Output (CMIMO) system is to improve network throughput and network coverage and save energy. By grouping wireless devices as virtual multi-antenna nodes, it can thus simulate the functions of multi-antenna systems. A Space-Time Block Code (STBC) was proposed to utilize the spatial diversity of MIMO systems to improve the diversity gain and coding gain. In this paper, we proposed a cooperative strategy based on STBC and CMIMO, which is referred to as Space-Time Block Coded Cooperative Multiple-Input Multiple-Output (STBC-CMIMO) to inherit the advantages from both STBC and CMIMO. The theoretical performance analysis for the proposed STBC-CMIMO is presented. The performance advantages of the STBC-CMIMO are also shown by simulations. In the simulations, it is demonstrated that STBC-CMIMO can obtain significant performance compared with the existing CMIMO system.

Synovial Fluid Interleukin-16 Contributes to Osteoclast Activation and Bone Loss through the JNK/NFATc1 Signaling Cascade in Patients with Periprosthetic Joint Infection.

Because of lipopolysaccharide (LPS)-mediated effects on osteoclast differentiation and bone loss, periprosthetic joint infection (PJI) caused by Gram-negative bacteria increases the risk of aseptic loosening after reimplantation. Synovial fluid interleukin-16 (IL-16) expression was higher in patients with PJI than in patients without joint infection. Thus, we explored the effects of IL-16 on bone. We investigated whether IL-16 modulates osteoclast or osteoblast differentiation in vitro. An LPS-induced bone loss mice model was used to explore the possible advantages of IL-16 inhibition for the prevention of bone loss. IL-16 directly activated p38 and c-Jun N-terminal kinase (JNK)/mitogen-activated protein kinase (MAPK) signaling and increased osteoclast activation markers, including tartrate-resistant acid phosphatase (TRAP), cathepsin K, and nuclear factor of activated T cells 1 (NFATc1). IL-16 directly caused monocytes to differentiate into TRAP-positive osteoclast-like cells through NFATc1 activation dependent on JNK/MAPK signaling. Moreover, IL-16 did not alter alkaline phosphatase activity or calcium deposition during osteoblastic differentiation. Finally, IL-16 inhibition prevented LPS-induced trabecular bone loss and osteoclast activation in vivo. IL-16 directly increased osteoclast activation through the JNK/NFATc1 pathway. IL-16 inhibition could represent a new strategy for treating infection-associated bone loss.

Heat-shock protein B1 upholds the cytoplasm reduced state to inhibit activation of the Hippo pathway in H9c2 cells.

Heat-shock protein B1 (HSPB1) is a multifunctional protein that protects against oxidative stress; however, its function in antioxidant pathways remains largely unknown. Here, we sought to determine the roles of HSPB1 in H9c2 cells subjected to oxidative stress. Using nonreducing sodium dodecyl sulfate polyacrylamide gel electrophoresis, we found that increased HSPB1 expression promoted the reduced states of glutathione reductase (GR), peroxiredoxin 1 (Prx1), and thioredoxin 1, whereas knockdown of HSPB1 attenuated these responses following oxidative stress. Increased HSPB1 expression promoted the activation of GR and thioredoxin reductase. Conversely, knockdown of HSPB1 attenuated these responses following oxidative stress. Importantly, overexpression of HSPB1 promoted the complex formation between HSPB1 and oxidized Prx1, leading to dephosphorylation of STE-mammalian STE20-like kinase 1 (MST1) in H9c2 cells exposed to H2 O 2 , whereas downregulation of HSPB1 induced the opposite results. Mechanistically, HSPB1 regulated the Hippo pathway by enhancing the dephosphorylation of MST1, resulting in reduced phosphorylation of LATS1 and Yes-associated protein (YAP). Moreover, HSPB1 regulated YAP-dependent gene expression. Thus, HSPB1 promoted the reduced state of endogenous antioxidant pathways following oxidative stress in H9c2 cells and improved the redox state of the cytoplasm via modulation of the Hippo signaling pathway.

Short-term toxicity of dibutyl phthalate to mice intestinal tissue.

The objective of this study was to investigate changes in intestinal histopathology and expression of heat-shock proteins (HSPs) in the small intestinal tissue of mouse after acute exposure to dibutyl phthalate (DBP). Forty-eight 60-day-old Institute of Cancer Research (ICR) mice were administered DBP by gavage once a day for 10 days. The mice were divided into three groups of 16 mice each: the high-dose group was administered 500 mg/kg body weight (BW) DBP; the low-dose group was administered 50 mg/kg BW; and the control group was not administered DBP. Significant increases in the uterine index, ovary index, and testicular index were observed in the DBP-exposed groups compared to those in the control group. Villus height and V/ C ratio significantly increased ( p < 0.05) in the duodenum and decreased ( p < 0.05) in the jejunum after the administration of DBP. The goblet cell number decreased in both the duodenum and the jejunum of mice exposed to DBP ( p < 0.05) compared to the number in the control group mice. Damage to the structure of the small intestine was accompanied by a marked increase in HSP27 expression and a decrease in the expression of HSP70 and HSP90 in both high-dose and low-dose groups. These results indicate that elevated HSP27 levels in the duodenum and jejunum may be important markers for acute DBP exposure and that HSP27 may act as a protective protein involved in intestinal mucosa repair.

Sample size adjustment based on promising interim results and its application in confirmatory clinical trials.

BACKGROUND: For a carefully planned and well-designed Phase 3 confirmatory trial, there is still a potential risk of failing to meet the study objective due to possible differences between Phase 2 and Phase 3 studies. As illustrated by the ENGAGE trial, potential sample size increase at an interim analysis can mitigate the risk for an otherwise underpowered study. Many approaches for sample size adjustment (SSA) require certain modifications to the conventional statistical method, such as changing critical values or using a weighted Z-statistic for final hypothesis testing. Without modification, the type I error rate can be inflated, primarily caused by sample size increase for nonpromising interim observation that is close to null or no treatment effect. As illustrated by the TOPICAL trial, increasing sample size for nonpromising interim result could waste limited resource on ineffective treatment. The modifications in these approaches are therefore unnecessary costs of flexibility/interpretability for unnecessary scenarios of sample size increase. PURPOSE: To discuss and illustrate the appropriateness of SSA based on promising interim results, that is, conditional power being greater than 50% (or CDL approach), in a carefully planned and well-designed Phase 3 confirmatory trial. METHODS: Two clinical trials are used to illustrate the clinical setting for the CDL approach and appropriateness of its application. Operating characteristics are assessed and compared to other methods using numeric computation. Hypothetical trials based on real clinical data are used to illustrate the approach. RESULTS: The CDL approach for SSA leads to a small increase in expected sample size resulting in a small power gain versus the fixed design. This indicates that adding SSA will not on average substantially affect the budget at the portfolio level. However, when the interim result is promising, the CDL approach can dramatically increase the conditional power therefore mitigating the risk of an otherwise underpowered study. LIMITATIONS: Implementation challenges of the SSA methods are not in the scope of this paper. SSA is not intended to replace careful design of a confirmatory trial; instead, it can mitigate the risk for a well-designed trial. CONCLUSIONS: The CDL approach for SSA based on promising interim results, that is, conditional power being greater than 50%, is particularly useful in mitigating the risk for a carefully planned and well-designed Phase 3 confirmatory trial. No modification to the conventional statistical procedure is necessary while the type I error rate is controlled. Such a feature of ''no interference,'' or no change to the conventional statistical procedure with or without sample size adjustment, is important for the interpretation of a confirmatory trial. Similar to the fixed design, carefully planned and well-designed group sequential studies can also benefit from SSA to mitigate the risk of failing to meet the study objective.

Silencing BMAL1 promotes M1/M2 polarization through the LDHA/lactate axis to promote GBM sensitivity to bevacizumab.

OBJECTIVE: Glioblastoma (GBM) has poor clinical prognosis due to limited treatment options. In addition, the current treatment regimens for GBM may only slightly prolong patient survival. The aim of this study was to assess the role of BMAL1 in the immune microenvironment and drug resistance of GBM. METHODS: GBM cell lines with stable BMAL1 knockdown or LDHA overexpression were constructed, and functionally characterized by the CCK8, EdU incorporation, and transwell assays. In vivo GBM model was established in C57BL/6J mice. Flow cytometry, ELISA, immunofluorescence, and RT-qPCR were performed to detect macrophage polarization. Lactate production, pathological changes, and the expression of glycolytic proteins were analyzed by HE staining, immunohistochemistry, biochemical assays, and Western blotting. RESULTS: BMAL1 silencing inhibited the malignant characteristics, lactate production, and expression of glycolytic proteins in GBM cells, and these changes were abrogated by overexpression of LDHA or exogenous lactate supplementation. Furthermore, BMAL1 knockdown induced M1 polarization of macrophages, and inhibited M2 polarization and angiogenesis in GBM cells in conditioned media. Overexpression of LDHA or presence of exogenous lactate inhibited BMAL1-induced M1 polarization and angiogenesis. Finally, BMAL1 silencing and bevacizumab synergistically inhibited glycolysis, angiogenesis and M2 polarization, and promoted M1 polarization in vivo, thereby suppressing GBM growth. CONCLUSION: BMAL1 silencing can sensitize GBM cells to bevacizumab by promoting M1/M2 polarization through the LDHA/lactate axis.

Total Glucosides of Paeony Ameliorate Myocardial Injury in Chronic Heart Failure Rats by Suppressing PARP-1.

Total glucosides of paeony (TGP) have a potential protective effect on chronic heart failure (CHF) rats, but the mechanism remains unclear. PARP inhibition prevents the decrease in myocardial contractility. Therefore, we aim to investigate the effects and mechanisms of TGP on CHF and the role of PARP-1 in CHF. Left anterior descending ligation rats and adriamycin-treated H9C9 cells were used as CHF models, and captopril as a positive control for in vivo experiments. We found that TGP alleviated myocardial remodeling and improved cardiac morphology and function. TGP also reduced myocardial apoptosis and autophagy, decreased inflammatory factor release, and inhibited the PARP-1 and NF-κB proteins. Through cell transfection, we found that PAPR-1 knockdown inhibited NF-κB nuclear translocation. Additionally, TGP inhibited apoptosis, autophagy, and inflammation in CHF cells, while PARP-1 overexpression partially antagonized them. In conclusion, TGP has the potential to improve CHF and PARP-1 may be a potential target.

Induction of Hibernation and Changes in Physiological and Metabolic Indices in Pelodiscus sinensis.

Pelodiscus sinensis (P. sinensis) is a commonly cultivated turtle species with a habit of hibernation. To study the changes in histone expression and methylation of P. sinensis during hibernation induction, a model was established by artificial induction. Physiological and metabolic indices were measured, and the expression and localization of histone (H1, H2A, H2B, H3, and H4) and methylation-related genes (ASH2L, KMT2A, KMT2E, KDM1A, KDM1B, and KDM5A) were measured by quantitative PCR, immunohistochemistry, and Western blot analysis. The results indicated that the metabolism, antioxidation index, and relative expression of histone methyltransferase were significantly decreased (p < 0.05), whereas the activity and expression of histone demethyltransferase were significantly increased (p < 0.05). Although our results showed significant changes in physiological and gene expression after hibernation induction, we could not confirm that P. sinensis entered deep hibernation. Therefore, for the state after cooling-induced hibernation, cold torpor might be a more accurate description. The results indicate that the P. sinensis can enter cold torpor through artificial induction, and the expression of histones may promote gene transcription. Unlike histones expressed under normal conditions, histone methylation may activate gene transcription during hibernation induction. Western blot analysis revealed that the ASH2L and KDM5A proteins were differentially expressed in the testis at different months (p < 0.05), which may perform a role in regulating gene transcription. The immunohistochemical localization of ASH2L and KDM5A in spermatogonia and spermatozoa suggests that ASH2L and KDM5A may perform a role in mitosis and meiosis. In conclusion, this study is the first to report changes in histone-related genes in reptiles, which provides insight for further studies on the physiological metabolism and histone methylation regulation of P. sinensis during the hibernation induction and hibernation period.

Exercise improves cardiac function and attenuates myocardial inflammation and apoptosis by regulating APJ/STAT3 in mice with stroke.

Stroke can induce cardiac dysfunction without a primary cardiac disease. Exercise can promote the overall rehabilitation of stroke patients and be beneficial for all kinds of heart diseases. However, the mechanisms underlying the protective effects of exercise in stroke-induced cardiac dysfunction are poorly understood. Hence, we aimed to distinguish the different effects of acute and long-term exercise and further study the mechanism of protection against cardiomyopathy caused by stroke. Mice underwent a single acute session or long-term exercise for 30 days, followed by middle cerebral artery occlusion surgery. The expression of apoptosis-related proteins and proinflammatory factors in the heart was evaluated. Then, overexpression of apelin peptide jejunum (APJ) transfected adeno-associated virus type 9 (AAV9) and inhibition of signal transducer and activator of transcription 3 (STAT3) by Stattic were used in stroke mice or hypoxic cardiomyocytes. ML221 were used to inhibit APJ activity in exercise mouse. Thereafter, changes in apoptotic and proinflammatory factors were evaluated. The results demonstrated that chronic exercise prevented myocardial inflammation, apoptosis and cardiac dysfunction after stroke. However, acute exercise did not have similar effects. Exercise maintained the levels of APJ expression and decreased phosphorylated-STAT3 (p-STAT3) activation to protect cardiomyocytes. Moreover, APJ overexpression promoted cardiomyocyte survival and reduced p-STAT3 levels. STAT3 inhibition also reduced apoptosis and proinflammatory factors in mice hearts. Conversely, the protective effect of exercise was eliminated by APJ inhibition. This study showed that exercise can maintain APJ expression and inhibit p-STAT3, thus, conferring protection against myocardial inflammation and apoptosis induced by stroke.

Importance of comprehensive genetic testing for patients with suspected vascular Ehlers-Danlos syndrome: a family case report and literature review.

Vascular Ehlers-Danlos syndrome (vEDS), the most severe type of Ehlers-Danlos syndrome, is caused by an autosomal-dominant defect in the COL3A1 gene. In this report, we describe the clinical history, specific phenotype, and genetic diagnosis of a man who died of vEDS. The precise diagnosis of this case using whole-exome sequencing provided solid evidence for the cause of death, demonstrating the practical value of genetic counseling and analysis. Early diagnosis for the proband's son, who was also affected by vEDS, revealed initial complications of vEDS in early childhood, which have rarely been reported. We also reviewed the literature on COL3A1 missense mutations and related phenotypes. We identified an association between digestion tract events and non-glycine missense variants, which disproves a previous hypothesis regarding the genotype-phenotype correlation of vEDS. Our results demonstrate the necessity of offering comprehensive genetic testing for every patient suspected of having vEDS.

[Digit length ratio and male fertility among infertile patients in Ningxia].

OBJECTIVE: To investigate the association between the digit length ratio (DLR) and male fertility in Ningxia. METHODS: Using an electronic sliding caliper, we measured the lengths of the index finger (D2), middle finger (D3), ring finger (D4) and little finger (D5) of both the right and left hand of 136 infertile males in Ningxia, 45 of them with normal and the other 91 with abnormal semen, including 28 cases of oligozoospermia, 10 cases of obstructive azoospermia (OA) and 53 cases of nonobstructive azoospermia (NOA). We calculated the DLRs of D2:D3, D2:D4, D2:D5, D3:D4, D3:D5 and D4:D5 and compared them among different groups. RESULTS: The mean values of FLR presented a pattern of D2:D3 < D2:D4 < D3:D4 < D2:D5 < D4:D5 in the infertile males. DLRs of D2:D3, D2:D4, D2:D5, D3:D5 and D4:D5 of the right hand were significantly higher in the abnormal than in the normal semen group (t = 2.56, 2.48, 3.57, 2.85, 2.53; P < 0.05); those of D2:D3, D2:D4, D2:D5 and D4:D5 of the right hand presented a pattern of NOA > oligozoospermia > OA > normal semen group, while that of D3:D5 presented a pattern of NOA > OA > oligozoospermia > normal semen group. The NOA group showed a significantly higher DLR of the right hand than the normal semen group in D2:D3, D2:D4, D3:D5 and D4:D5, the oligozoospermia group in D2:D4, D3:D5 and D4:D5, and the OA group in D2:D3 (P < 0.05). The D4:D5 DLR of the right hand was remarkably higher in the Han than in the Hui ethnic group (t = 2.01, P < 0.05). CONCLUSION: Higher DLRs of D2:D3, D2:D4, D2:D5, D3:D5 and D4:D5 of the right hand were associated with lower fertility in infertile males in Ningxia. And the D4:D5 FLRs of the right hand may be different between Hui and Han infertile men in Ningxia.

Protection and Damage Repair Mechanisms Contributed To the Survival of Chroococcidiopsis sp. Exposed To a Mars-Like Near Space Environment.

Chroococcidiopsis spp. can withstand extremely harsh environments, including a Mars-like environment. However, studies are lacking on the molecular mechanisms of Chroococcidiopsis sp. surviving in Mars-like environments. In the HH-21-5 mission, the desert cyanobacterium Chroococcidiopsis sp. was exposed to a Mars-like environment (near space; 35 km altitude) for 4 h, and a single-factor environment of near space was simulated on the ground. We investigated the survival and endurance mechanisms of Chroococcidiopsis sp. ASB-02 after exposing it to near space by studying its physiological and transcriptional properties. After the exposure, Chroococcidiopsis sp. ASB-02 exhibited high cell viability, although photosystem II activity decreased and the levels of reactive oxygen species increased. The single-factor simulation experiments revealed that for the survival of Chroococcidiopsis sp. ASB-02 in near space, UV radiation was the most important limiting factor, and it was followed by temperature. The near space environment triggered multiple metabolic pathway responses in Chroococcidiopsis sp. ASB-02. The upregulation of extracellular polysaccharides as well as carotenoid and scytonemin biosynthesis genes in response to UV radiation attenuated the extent of radiation reaching the cells. At the same time, genes related to protein synthesis were upregulated in response to the low temperature, overcoming the decrease in metabolic activity that was caused by the low temperature. In near space and after rehydration, the genes involved in various DNA and photosystem II repair pathways were upregulated. This reflected the damage to the DNA and photosystem II protein subunits in cells during the flight and suggested that repair mechanisms play an important role in the recovery of Chroococcidiopsis sp. ASB-02. IMPORTANCE This study reported that the protective and repair mechanisms of Chroococcidiopsis sp. ASB-02 contributed to its endurance ability in a Mars-like near space environment. In Chroococcidiopsis sp. ASB-02, a Mars-like near space environment activated the expression of genes involved in extracellular polysaccharides (EPS), carotenoid, scytonemin, and protein syntheses, which provided additional protection. Additionally, the cell damage repair process enhanced the recovery rate of Chroococcidiopsis sp. ASB-02 after the flight. This study will help to enhance the understanding of the tolerance mechanism of Chroococcidiopsis sp. and to provide important guidance as to the survival requirements for microbial life in a Mars-like environment.

Friend or foe: RIG- I like receptors and diseases.

Retinoic acid-inducible gene I (RIG-I)-like receptors (RLRs), which are pivotal sensors of RNA virus invasions, mediate the transcriptional induction of genes encoding type I interferons (IFNs) and proinflammatory cytokines, successfully establishing host antiviral immune response. A few excellent reviews have elaborated on the structural biology of RLRs and the antiviral mechanisms of RLR activation. In this review, we give a basic understanding of RLR biology and summarize recent findings of how RLR signaling cascade is strictly controlled by host regulatory mechanisms, which include RLR-interacting proteins, post-translational modifications and microRNAs (miRNAs). Furthermore, we pay particular attention to the relationship between RLRs and diseases, especially how RLRs participate in SARS-CoV-2, malaria or bacterial infections, how single-nucleotide polymorphisms (SNPs) or mutations in RLRs and antibodies against RLRs lead to autoinflammatory diseases and autoimmune diseases, and how RLRs are involved in anti-tumor immunity. These findings will provide insights and guidance for antiviral and immunomodulatory therapies targeting RLRs.