Nickel-catalysed regio- and stereoselective hydrocyanation of alkynoates and its mechanistic insights proposed by DFT calculations.

We have developed a nickel-catalysed regio- and stereoselective hydrocyanation of alkynoates that gives syn-ß-cyanoalkenes. DFT calculations suggest that a favored transition state promotes Cα-H bond formation for determining regio- and stereoselectivity of the products.

Diverse adolescents' transcendent thinking predicts young adult psychosocial outcomes via brain network development.

Developmental scientists have long described mid-adolescents' emerging capacities to make deep meaning about the social world and self, here called transcendent thinking, as a hallmark developmental stage. In this 5-years longitudinal study, sixty-five 14-18 years-old youths' proclivities to grapple psychologically with the ethical, systems-level and personal implications of social stories, predicted future increases in the coordination of two key brain networks: the default-mode network, involved in reflective, autobiographical and free-form thinking, and the executive control network, involved in effortful, focused thinking; findings were independent of IQ, ethnicity, and socioeconomic background. This neural development predicted late-adolescent identity development, which predicted young-adult self-liking and relationship satisfaction, in a developmental cascade. The findings reveal a novel predictor of mid-adolescents' neural development, and suggest the importance of attending to adolescents' proclivities to engage agentically with complex perspectives and emotions on the social and personal relevance of issues, such as through civically minded educational approaches.

Metallaaromatic Complexes as Candidates for Future Molecular Materials and Electronic Devices: Recent Advancements.

In recent years, the field of organometallic chemistry has made a great progress and diverse types of metallaaromatics have successively been reported. In those studies, incorporation of ligated osmium centers into metallaaromatic systems played a prominent role. The reviewed literature documents that certain metallaaromatics with unconventional photophysical properties, redox and electronic transport properties and magnetism, have potential to be widely used in diverse practical applications, with selected examples of amino acid and fluoride anion identification, photothermal effects, functional materials, photodynamic therapy (PDT) in biomedicine, single-molecule junction conductors, and electron-transport layer materials (ETLs) in solar cells.

Central and peripheral analgesic active components of triterpenoid saponins from Stauntonia chinensis and their action mechanism.

Triterpenoid saponins from Stauntonia chinensis have been proven to be a potential candidate for inflammatory pain relief. Our pharmacological studies confirmed that the analgesic role of triterpenoid saponins from S. chinensis occurred via a particular increase in the inhibitory synaptic response in the cortex at resting state and the modulation of the capsaicin receptor. However, its analgesic active components and whether its analgesic mechanism are limited to this are not clear. In order to further determine its active components and analgesic mechanism, we used the patch clamp technique to screen the chemical components that can increase inhibitory synaptic response and antagonize transient receptor potential vanilloid 1, and then used in vivo animal experiments to evaluate the analgesic effect of the selected chemical components. Finally, we used the patch clamp technique and molecular biology technology to study the analgesic mechanism of the selected chemical components. The results showed that triterpenoid saponins from S. chinensis could enhance the inhibitory synaptic effect and antagonize the transient receptor potential vanilloid 1 through different chemical components, and produce central and peripheral analgesic effects. The above results fully reflect that "traditional Chinese medicine has multi-component, multi-target, and multi-channel synergistic regulation".

The safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine among patients undergoing elective surgery for closed fractures: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial.

BACKGROUND: Vaccines are urgently required to control Staphylococcus aureus hospital and community infections and reduce the use of antibiotics. Here, we report the safety and immunogenicity of a recombinant five-antigen Staphylococcus aureus vaccine (rFSAV) in patients undergoing elective surgery for closed fractures. METHODS: A randomized, double-blind, placebo-controlled, multicenter phase 2 clinical trial was carried out in 10 clinical research centers in China. Patients undergoing elective surgery for closed fractures, aged 18-70 years, were randomly allocated at a ratio of 1:1 to receive the rFSAV or placebo at a regimen of two doses on day 0 and another dose on day 7. All participants and investigators remained blinded during the study period. The safety endpoint was the incidence of adverse events within 180 days. The immunogenicity endpoints included the level of specific antibodies to five antigens after vaccination, as well as opsonophagocytic antibodies. RESULTS: A total of 348 eligible participants were randomized to the rFSAV (n = 174) and placebo (n = 174) groups. No grade 3 local adverse events occurred. There was no significant difference in the incidence of overall systemic adverse events between the experimental (40.24 %) and control groups (33.72 %) within 180 days after the first immunization. The antigen-specific binding antibodies started to increase at days 7 and reached their peaks at 10-14 days after the first immunization. The rapid and potent opsonophagocytic antibodies were also substantially above the background levels. CONCLUSIONS: rFSAV is safe and well-tolerated in patients undergoing elective surgery for closed fractures. It elicited rapid and robust specific humoral immune responses using the perioperative immunization procedure. These results provide evidence for further clinical trials to confirm the vaccine efficacy. China's Drug Clinical Trials Registration and Information Publicity Platform registration number: CTR20181788. WHO International Clinical Trial Registry Platform identifier: ChiCTR2200066259.

Single-cell analyses reveal distinct expression patterns and roles of long non-coding RNAs during hESC differentiation into pancreatic progenitors.

BACKGROUND: Deep understanding the differentiation process of human embryonic stem cells (hESCs) is essential for developing cell-based therapeutic strategy. Substantial efforts have been made to investigate protein-coding genes, yet it remains lacking comprehensive characterization of long non-coding RNAs (lncRNAs) during this process. METHODS: hESCs were passaged every 5-6 days and had maintained stable karyotype even until the 50th generation. Pancreatic progenitor specification of in vitro differentiation from hESCs was performed and modified. The nuclei were stained with 4,6-Diamidino-2-phenylindole (DAPI). Droplet-based platform (10X Genomics) was applied to generate the single-cell RNA sequencing (scRNA-seq) data. The quality of the filtered read pairs was evaluated by using FastQC. Batch effects were removed using the size factor method. Dimension reduction and unsupervised clustering analyses were performed using Seurat R package. The Monocle 2 and MetaCell algorithms were used to order single cells on a pseudotime course and partition the scRNA-seq data into metacells, respectively. Co-expression network was constructed using WGCNA. Module- and hub-based methods were adopted to predict the functions of lncRNAs. RESULTS: A total of 77,382 cells during the differentiation process of hESCs toward pancreatic progenitors were sequenced. According to the single-cell map, the cells from different time points were authenticated to constitute a relatively homogeneous population, in which a total of 7382 lncRNAs could be detected. Through further analyzing the time course data, conserved and specific expression features of lncRNAs during hESC differentiation were revealed. Based upon pseudotime analysis, 52 pseudotime-associated lncRNAs that grouped into three distinct expression patterns were identified. We also implemented MetaCell algorithm and network-based methods to explore the functional mechanisms of these lncRNAs. Totally, 464 lncRNAs, including 49 pseudotime-associated lncRNAs were functionally annotated by either module-based or hub-based methods. Most importantly, we demonstrated that the lncRNA HOTAIRM1, which co-localized and co-expressed with several HOX genes, may play crucial role in the generation of pancreatic progenitors through regulation of exocytosis and retinoic acid receptor signaling pathway. CONCLUSIONS: Our single-cell analyses provide valuable data resources for biological researchers and novel insights into hESC differentiation processes, which will guide future endeavors to further elucidate the roles of lncRNAs.

Antioxidants attenuate mitochondrial oxidative damage through the Nrf2 pathway: A promising therapeutic strategy for stroke.

Stroke represents one of the leading causes of disability and death worldwide. Reactive oxygen species overproduction-induced oxidative stress in mitochondria results in mitochondrial DNA damage, mitochondrial autophagy (mitophagy), inflammation, and apoptosis during the pathologic progression of stroke. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a master regulator that induces the transcription of a wide range of antioxidant genes to attenuate mitochondrial oxidative stress. Different antioxidative compounds, including polyphenols, mitochondrial antioxidants, triterpenoids, and others, have been shown to be able to activate Nrf2 and, thus, exert neuroprotective effects on stroke by ameliorating mitochondrial oxidative damage. In this review, we briefly discussed the role of mitochondrial oxidative stress in the pathophysiology of stroke and focused on the protective effects of antioxidative compounds through attenuating mitochondrial oxidative damage by activating Nrf2 in stroke. In conclusion, these antioxidants may represent novel therapeutic strategies against stroke.

Echinocystic acid alleviated hypoxic-ischemic brain damage in neonatal mice by activating the PI3K/Akt/Nrf2 signaling pathway.

Neonatal hypoxic-ischemic encephalopathy (HIE) is considered a major cause of death and long-term neurological injury in newborns. Studies have demonstrated that oxidative stress and apoptosis play a major role in the progression of neonatal HIE. Echinocystic acid (EA), a natural plant extract, shows great antioxidant and antiapoptotic activities in various diseases. However, it has not yet been reported whether EA exerts a neuroprotective effect against neonatal HIE. Therefore, this study was undertaken to explore the neuroprotective effects and potential mechanisms of EA in neonatal HIE using in vivo and in vitro experiments. In the in vivo study, a hypoxic-ischemic brain damage (HIBD) model was established in neonatal mice, and EA was administered immediately after HIBD. Cerebral infarction, brain atrophy and long-term neurobehavioral deficits were measured. Hematoxylin and eosin (H&E), terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) and dihydroethidium (DHE) staining were performed, and the contents of malondialdehyde (MDA) and glutathione (GSH) were detected. In the in vitro study, an oxygen-glucose deprivation/reperfusion (OGD/R) model was employed in primary cortical neurons, and EA was introduced during OGD/R. Cell death and cellular ROS levels were determined. To illustrate the mechanism, the PI3K inhibitor LY294002 and Nrf2 inhibitor ML385 were used. The protein expression levels of p-PI3K, PI3K, p-Akt, Akt, Nrf2, NQO1, and HO-1 were measured by western blotting. The results showed that EA treatment significantly reduced cerebral infarction, attenuated neuronal injury, and improved brain atrophy and long-term neurobehavioral deficits in neonatal mice subjected to HIBD. Meanwhile, EA effectively increased the survival rate in neurons exposed to OGD/R and inhibited oxidative stress and apoptosis in both in vivo and in vitro studies. Moreover, EA activated the PI3K/Akt/Nrf2 pathway in neonatal mice following HIBD and in neurons after OGD/R. In conclusion, these results suggested that EA alleviated HIBD by ameliorating oxidative stress and apoptosis via activation of the PI3K/Akt/Nrf2 signaling pathway.

Effect of pegylated interferon-α2b add-on therapy on renal function in chronic hepatitis B patients: A real-world experience.

Background and aim: Controversy remains as to pegylated interferon-α (PEG-IFNα) antiviral therapy to renal function in chronic hepatitis B (CHB) patients. The aim of this study was to evaluate the influence of PEG-IFNα2b (Y shape, 40 kD) add-on treatment for renal function in CHB patients who received entecavir therapy. Methods: This was a retrospective observational study to investigate factors related to renal function in 114 CHB patients who received PEG-IFNα2b add-on therapy to entecavir for 48 weeks. Changes of blood urea nitrogen (BUN), serum creatinine (sCr), and estimated glomerular filtration rate (eGFR), which was calculated with both Chronic Kidney Disease Epidemiology Collaboration and Modification of Diet in Renal Disease (MDRD) formulas, were analyzed by one-way analysis of variance. A linear mixed effects model for repeated measures was used to assess the correlation between baseline information and eGFR changes at 24 and 48 weeks of therapy. The model considered the baseline age, gender, body weight, viral load, hepatitis B surface antigen, BUN, sCr, and treatment strategy as fixed effects and incorporated random effects for individual subjects. Results: BUN and sCr was decreased, while eGFR was increased at 12 weeks of therapy. Only eGFR maintained at 24 and 48 weeks of therapy. Patients with female gender, age ≥ 40 years, and baseline HBsAg level < 250 IU/mL showed significant improvement of renal function with PEG-IFNα2b add-on therapy. The linear mixed effects model revealed that female gender, baseline sCr, and PEG-IFNα2b add-on were significant positive predictors for eGFR elevation at 24 and 48 weeks of therapy. Conclusion: In real-world experience, PEG-IFNα2b add-on therapy might be associated with increased eGFR in CHB patients.

[Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with inv(16)/t(16;16)(p13.1;q22) and/or CBFß-MYH11].

OBJECTIVE: To summarize the clinical and laboratory characteristics of patients with acute myeloid leukemia (AML) with inv(16)/t(16;16) (p13.1;q22), and to analyze the risk factors affecting the prognosis of the patients. METHODS: AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFß-MYH11+ admitted to the Department of Hematology, The First Affiliated Hospital of Soochow University from January 1, 2008 to October 30, 2019 were retrospective analyzed, the clinical and laboratory indicators, as well as treatment plans and efficacy evaluations of the patients were all recorded. Furthermore, related factors affecting the overall survival (OS) and event-free survival (EFS) of the patients were analyzed. RESULTS: Among 151 AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFß-MYH11+, the percentage of additional chromosomal abnormalities was about 27.8%, and the most common additional chromosomal abnormality was +22 (33/151, 21.8%), followed by +8 (11/151, 7.3%). There were 112 patients with perfect NGS examination, and the result showed the most common accompanying gene mutations were KIT mutation (34/112, 30.4%) and FLT3 mutation (23/112, 20.5%). Univariate analysis showed that factors affecting EFS included: NE≤0.5×109/L (P=0.006) and combined K-RAS mutation (P=0.002); Factors affecting OS included: Age≥50 years old (P<0.001) and NE≤0.5×109/L (P=0.016). Multivariate analysis showed that NE≤0.5×109/L (P=0.019) was the risk factors affecting OS. The proportion of bone marrow eosinophilia (BME)≥10.00% (P=0.029) was the risk factors affecting EFS. CONCLUSION: The prognosis for those newly diagnosed AML patients who were of advanced age, the high proportion of bone marrow eosinophils, K-RAS mutations, and agranulocytosis is poor. The treatment plans can be adjusted in the early stage to improve the prognosis of such patients.

[Clinical Characteristics and Prognosis of Acute Myeloid Leukemia Patients with inv(16)/t(16;16)(p13.1;q22) and/or CBFß-MYH11].

OBJECTIVE: To summarize the clinical and laboratory characteristics of patients with acute myeloid leukemia (AML) with inv(16)/t(16;16) (p13.1;q22), and to analyze the risk factors affecting the prognosis of the patients. METHODS: AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFß-MYH11+ admitted to the Department of Hematology, The First Affiliated Hospital of Soochow University from January 1, 2008 to October 30, 2019 were retrospective analyzed, the clinical and laboratory indicators, as well as treatment plans and efficacy evaluations of the patients were all recorded. Furthermore, related factors affecting the overall survival (OS) and event-free survival (EFS) of the patients were analyzed. RESULTS: Among 151 AML patients with inv(16)/t(16;16) (p13.1;q22) and/or CBFß-MYH11+, the percentage of additional chromosomal abnormalities was about 27.8%, and the most common additional chromosomal abnormality was +22 (33/151, 21.8%), followed by +8 (11/151, 7.3%). There were 112 patients with perfect NGS examination, and the result showed the most common accompanying gene mutations were KIT mutation (34/112, 30.4%) and FLT3 mutation (23/112, 20.5%). Univariate analysis showed that factors affecting EFS included: NE≤0.5×109/L (P=0.006) and combined K-RAS mutation (P=0.002); Factors affecting OS included: Age≥50 years old (P<0.001) and NE≤0.5×109/L (P=0.016). Multivariate analysis showed that NE≤0.5×109/L (P=0.019) was the risk factors affecting OS. The proportion of bone marrow eosinophilia (BME)≥10.00% (P=0.029) was the risk factors affecting EFS. CONCLUSION: The prognosis for those newly diagnosed AML patients who were of advanced age, the high proportion of bone marrow eosinophils, K-RAS mutations, and agranulocytosis is poor. The treatment plans can be adjusted in the early stage to improve the prognosis of such patients.

Integrative analysis reveals a lineage-specific circular RNA landscape for adipo-osteogenesis of human mesenchymal stem cells.

BACKGROUND: The balance between osteogenesis and adipogenesis of mesenchymal stem cells (MSCs) is critical to skeletal development and diseases. As a research hotspot, circular RNAs (circRNAs) have expanded our understanding of a hidden layer of the transcriptome. Yet, their roles during adipo-osteogenesis remain poorly described. METHODS: The identity of human MSCs derived from bone marrow and adipose were first determined by flow cytometry, cellular staining, and quantitative polymerase chain reaction (qPCR). Multi-strategic RNA-sequencing was performed using Poly A, RiboMinus and RiboMinus/RNase R methods. Integrative analysis was performed to identify lineage-specific expressed circRNAs. The structural and expressional characteristics were identified by Sanger sequencing and qPCR, respectively. The regulatory effects of adipogenesis-specific circ-CRLF1 were confirmed using siRNA transcfection and qPCR. RESULTS: We generated a whole transcriptome map during adipo-osteogenesis based on 10 Poly A, 20 RiboMinus and 20 RiboMinus/ RNase R datasets. A total of 31,326 circRNAs were identified and quantified from ~ 3.4 billion paired-end reads. Furthermore, the integrative analysis revealed that 1166 circRNA genes exhibited strong lineage-specific expression patterns. Their host genes were enriched in distinct biological functions, such as cell adhesion, cytokine signaling, and cell division. We randomly selected and validated the back-spliced junction sites and expression patterns of 12 lineage-specific circRNAs. Functional analysis indicated that circ-CRLF1 negatively regulated adipogenesis. CONCLUSIONS: Our integrative analysis reveals an accurate and generally applicable lineage-specific circRNA landscape for adipo-osteogenesis of MSCs and provides a potential therapeutic target, circ-CRLF1, for the treatment of skeleton-related disease.

Genistein mitigates oxidative stress and inflammation by regulating Nrf2/HO-1 and NF-κB signaling pathways in hypoxic-ischemic brain damage in neonatal mice.

Background: Oxidative stress and neuroinflammation play crucial roles in the progression of neonatal hypoxic-ischemic brain damage (HIBD). Genistein, a natural phytoestrogen, has been found to protect against ischemic brain injury. However, its effects and potential mechanisms in HIBD have not yet been explored. Methods: A neonatal mouse model of hypoxia-ischemia (HI) and a cell model of oxygen-glucose deprivation/reperfusion (OGD/R) were employed. In the in vivo study, genistein (10 mg/kg; ip) was administered in mice once daily for 3 consecutive days before the operation and once immediately after HI. The effects of genistein treatment on acute brain damage and long-term responses were evaluated. Neuronal injury and apoptosis were estimated using hematoxylin and eosin (H&E) and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining, respectively. The expression of apoptosis-related proteins were also measured by Western blot analysis. Dihydroethidium (DHE) staining and glutathione (GSH) and malondialdehyde (MDA) production were determined to assess the extent of oxidative stress. The messenger RNA (mRNA) levels of proinflammatory cytokines were detected using real-time quantitative polymerase chain reaction (RT-qPCR) to evaluate the extent of neuroinflammation. In the in vitro study, cell counting kit-8 (CCK-8) and lactate dehydrogenase (LDH) assays, as well as propidium iodide (PI) staining, were performed to analyse the neuroprotective effects of genistein on primary cortical neurons. Western blot assays were used to detect the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), phosphorylated inhibitor kappa B-α (p-IκB-α) and phosphorylated nuclear factor-kappa B (p-NF-κB) both in vivo and in vitro. Results: Our results showed that genistein treatment effectively reduced cerebral infarction, attenuated neuronal injury and apoptosis, and contributed to the long-term recovery of neurological outcomes and brain atrophy in neonatal HIBD mice. Moreover, genistein ameliorated HIBD-induced oxidative stress and neuroinflammation. Meanwhile, genistein significantly increased cell viability, reversed neuronal injury and decreased cell apoptosis after OGD/R injury. Finally, the activation of the Nrf2/HO-1 pathway and inhibition of the NF-κB pathway by genistein were verified in the brain tissues of neonatal mice subjected to HIBD and in primary cortical neurons exposed to OGD/R. Conclusions: Genistein exerted neuroprotective effects on HIBD by attenuating oxidative stress and neuroinflammation through the Nrf2/HO-1 and NF-κB signalling pathways.

Ruxolitinib reduces severe CRS response by suspending CAR-T cell function instead of damaging CAR-T cells.

The therapeutic effect of CAR-T is often accompanied by sCRS, which is the main obstacle to the promotion of CAR-T therapy. The JAK1/2 inhibitor ruxolitinib has recently been confirmed as clinically effective in maintaining control over sCRS, however, its mechanism remains unclear. In this study, we firstly revealed that ruxolitinib significantly inhibited the proliferation of CAR-T cells without damaging viability, and induced an efficacy-favored differentiation phenotype. Second, ruxolitinib reduced the level of cytokine release not only from CAR-T cells, but also from other cells in the immune system. Third, the cytolytic activity of CAR-T cells was restored once the ruxolitinib was removed; however, the cytokines released from the CAR-T cells maintained an inhibited state to some degree. Finally, ruxolitinib significantly reduced the proliferation rate of CAR-T cells in vivo without affecting the therapeutic efficacy after withdrawal at the appropriate dose. We demonstrated pre-clinically that ruxolitinib interferes with both CAR-T cells and the other immune cells that play an important role in triggering sCRS reactions. This work provides useful and important scientific data for clinicians on the question of whether ruxolitinib has an effect on CAR-T cell function loss causing CAR-T treatment failure when applied in the treatment of sCRS, the answer to which is of great clinical significance.

Default and executive networks' roles in diverse adolescents' emotionally engaged construals of complex social issues.

Across adolescence, individuals enrich their concrete, empathic, context-specific interpretations of social-world happenings with abstract, situation-transcending, system-level considerations-invoking values, bigger implications and broader emotional perspectives. To investigate neural mechanisms involved in abstract construals vs concrete construals and the effects of emotional engagement on these mechanisms, 65 mid-adolescents aged 14-18 years reacted to compelling video mini-documentaries during private, open-ended interviews and again during functional magnetic resonance imaging. Following calls to diversify samples, participants were ethnically diverse low-socioeconomic status (SES) urban adolescents performing well in school. Participants spontaneously produced both concrete and abstract construals in the interview, and tendencies to produce each varied independently. As hypothesized, participants who made more abstract construals showed a greater subsequent default mode network (DMN) activity; those who made more concrete construals showed greater executive control network (ECN) activity. Findings were independent of IQ, SES, age and gender. Within individuals, DMN activation, especially when individuals were reporting strong emotional engagement, and ECN deactivation together predicted an abstract construal to a trial. Additionally, brief ECN activation early in the trial strengthened the DMN-abstraction relationship. Findings suggest a neural mechanism for abstract social thought in adolescence. They also link adolescents' natural construals of social situations to distinct networks' activity and suggest separable sociocognitive traits that may vary across youths.

Ureteroscopic holmium laser to transect the greater omentum to remove an abdominal drain: Four case reports.

BACKGROUND: Drainage tube removal is difficult when the greater omentum becomes incarcerated in the drainage tube through the side holes. Currently, known removal methods are either ineffective or will cause additional damage to the patient in a secondary operation. Ureteroscopy and the holmium laser have been used in various surgical techniques in urology, and in theory, they are expected to be a good strategy for solving the problem of tissue incarceration. CASE SUMMARY: Four patients diagnosed with difficult removal of an abdominal drainage tube following abdominal surgery are reported. All patients underwent surgery to remove the incarcerated greater omentum in the drainage tube using a holmium laser and a ureteroscope, and a new 16-F drain was then placed in the abdominal or pelvic cavity. The efficacy of this technique was evaluated by intraoperative conditions, success rate, and operating time; safety was evaluated by perioperative conditions and the probability of postoperative complications. All four operations went smoothly, and the drains were successfully removed in all patients. The average operating time was 24.5 min. Intraoperatively, the average irrigation volume was 892.0 mL, the average drainage volume was 638.5 mL, and no bleeding or damage to surrounding tissues was observed. Postoperatively, the average drainage volume was 32.8 mL and the new drains were removed within 36 h. All patients were able to get out of bed and move around within 12 h. Their visual analogue pain scores were all below 3. The average follow-up duration was 12.5 mo and no complications such as fever or bleeding were noted. CONCLUSION: Ureteroscopic holmium laser surgery is an effective, safe and minimally invasive technique for removing drains where the greater omentum is incarcerated in the abdominal drain.

A novel SARS-CoV-2 related coronavirus with complex recombination isolated from bats in Yunnan province, China.

At the end of 2019, A new type of beta-CoV, SARS-CoV-2 emerged and triggered the COVID-19 pandemic, which spread overwhelmingly around the world in less than a year. However, the origin and direct ancestral viruses of SARS-CoV-2 remain unknown. RaTG13, a novel coronavirus found in bats in China's Yunnan Province, is the closest relative virus of the SARS-CoV-2 identified so far. In this study, a new SARS-CoV-2 related virus, provisionally named PrC31, was discovered in Yunnan province by retrospectively analyse bat next generation sequencing (NGS) data of intestinal samples collected in 2018. PrC31 shared 90.7% and 92.0% nucleotide identities to the genomes of SARS-CoV-2 and the bat SARSr-CoV ZC45, respectively. Sequence alignment of PrC31 showed that several genomic regions, especially orf1a and orf8 had the highest homology with those corresponding genomic regions of SARS-CoV-2 than any other related viruses. Phylogenetic analysis indicated that PrC31 shared a common ancestor with SARS-CoV-2 in evolutionary history. The differences between the PrC31 and SARS-CoV-2 genomes were mainly manifested in the spike genes. The amino acid homology between the receptor binding domains of PrC31 and SARS-CoV-2 was only 64.2%. Importantly, recombination analysis revealed that PrC31 underwent multiple complex recombination events (including three recombination breakpoints) involving the SARS-CoV and SARS-CoV-2 sub-lineages, indicating that PrC31 evolved from yet-to-be-identified intermediate recombination strains. Combined with previous studies, it is revealed that the beta-CoVs may possess a more complex recombination mechanism than we thought.

Dissecting the multi-omics atlas of the exosomes released by human lung adenocarcinoma stem-like cells.

Lung adenocarcinoma is heterogeneous and hierarchically organized, with a subpopulation of stem-like cells (CSCs) that reside at the apex of the hierarchy, in which exosomes act as important mediators by transporting specific molecules among different cell populations. Although there have been numerous studies on tumor exosomes, the constituents and functional properties of CSC-derived exosomes are still poorly characterized. Here we present a detail transcriptome and proteome atlas of the exosomes released by human lung adenocarcinoma stem-like cells (LSLCs). The transcriptome analysis indicates the specific patterns of exosomal constituents, including the fragmentation of transcripts and the low-level presence of circular RNAs, and identifies multiple exosomal-enriched mRNAs and lncRNAs. Integrative analysis of transcriptome and proteome data reveals the diverse functions of exosomal-enriched RNAs and proteins, many of which are associated with tumorigenesis. Importantly, several LSLC markers we identified are highly expressed in LSLC-derived exosomes and associate with poor survival, which may serve as promising liquid biopsy biomarkers for lung adenocarcinoma diagnosis. Our study provides a resource for the future elucidation of the functions of tumor-derived exosomes and their regulatory mechanisms in mediating lung cancer development.

Biphalin, a dimeric opioid peptide, reduces neonatal hypoxia-ischemia brain injury in mice by the activation of PI3K/Akt signaling pathway.

Previous studies have demonstrated that the activation of delta opioid receptors is neuroprotective against neonatal hypoxia-ischemia (HI) brain injury. The aim of this study was to investigate the neuroprotective effects of biphalin, a dimeric opioid peptide, in a mouse model of neonatal HI and the underlying mechanisms. On postnatal day 10, mouse pups were subjected to unilateral carotid artery ligation followed by 1 h of hypoxia (10 % O2 in N2). For treatment, biphalin (5 mg/kg, 10 mg/kg, 20 mg/kg) was administered intraperitoneally immediately after HI. The opioid antagonist naloxone or phosphatidylinositol-3-kinase inhibitor Ly294002 was administered to determine the underlying mechanisms. Infarct volume, brain edema, phosphorylated Akt and apoptosis-related proteins levels were evaluated by using a combination of 2,3,5-triphenyltetrazolium chloride staining, brain water content and Western blotting at 24 h after HI. The long-term effects of biphalin were evaluated by brain atrophy measurement, Nissl staining and neurobehavioral tests at 3 weeks post-HI. Biphalin (10 mg/kg) significantly reduced the infarct volume and ameliorated brain edema. Biphalin also had long-term protective effects against the loss of ipsilateral brain tissue and resulted in improvements in neurobehavioral outcomes. However, naloxone or Ly294002 abrogated the neuroprotective effects of biphalin. Furthermore, biphalin treatment significantly preserved phosphorylated Akt expression, increased Bcl-2 levels, and decreased Bax and cleaved caspase 3 levels after HI. These effects were also reversed by naloxone and Ly294002 respectively. In conclusion, biphalin protects against HI brain injury in neonatal mice, which might be through activation of the opioid receptor/phosphatidylinositol-3-kinase/Akt signaling pathway.