Brain-Region-Specific Organoids Using Mini-bioreactors for Modeling ZIKV Exposure.

Cerebral organoids, three-dimensional cultures that model organogenesis, provide a new platform to investigate human brain development. High cost, variability, and tissue heterogeneity limit their broad applications. Here, we developed a miniaturized spinning bioreactor (SpinΩ) to generate forebrain-specific organoids from human iPSCs. These organoids recapitulate key features of human cortical development, including progenitor zone organization, neurogenesis, gene expression, and, notably, a distinct human-specific outer radial glia cell layer. We also developed protocols for midbrain and hypothalamic organoids. Finally, we employed the forebrain organoid platform to model Zika virus (ZIKV) exposure. Quantitative analyses revealed preferential, productive infection of neural progenitors with either African or Asian ZIKV strains. ZIKV infection leads to increased cell death and reduced proliferation, resulting in decreased neuronal cell-layer volume resembling microcephaly. Together, our brain-region-specific organoids and SpinΩ provide an accessible and versatile platform for modeling human brain development and disease and for compound testing, including potential ZIKV antiviral drugs.

Telemedicine network latency management system in 5G telesurgery: a feasibility and effectiveness study.

BACKGROUND: Network latency is the most important factor affecting the performance of telemedicine. The aim of the study is to assess the feasibility and efficacy of a novel network latency management system in 5G telesurgery. METHODS: We conducted 20 telesurgery simulation trials (hitching rings to columns) and 15 remote adrenalectomy procedures in the 5G network environment. Telemedicine Network Latency Management System and the traditional "Ping command" method (gold standard) were used to monitor network latency during preoperative simulated telesurgery and formal telesurgery. We observed the working status of the Telemedicine Network Latency Management System and calculated the difference between the network latency data and packet loss rate detected by the two methods. In addition, due to the lower latency of the 5G network, we tested the alert function of the system using the 4G network with relatively high network latency. RESULTS: The Telemedicine Network Latency Management System showed no instability during telesurgery simulation trials and formal telesurgery. After 20 telesurgery simulation trials and 15 remote adrenalectomy procedures, the p-value for the difference between the network latency data monitored by the Telemedicine Network Latency Management System and the "Ping command" method was greater than 0.05 in each case. Meanwhile, the surgeons reported that the Telemedicine Network Latency Management System had a friendly interface and was easy to operate. Besides, when the network latency exceeded a set threshold, a rapid alarm sounded in the system. CONCLUSION: The Telemedicine Network Latency Management System was simple and easy to operate, and it was feasible and effective to use it to monitor network latency in telesurgery. The system had an intuitive and concise interface, and its alarm function increased the safety of telesurgery. The system's own multidimensional working ability and information storage capacity will be more suitable for telemedicine work.

Gradient Nanoconfinement Facilitates Binding of Transcriptional Factor NF-κB to Histone- and Protamine-DNA Complexes.

Mechanically induced chromosome reorganization plays important roles in transcriptional regulation. However, the interplay between chromosome reorganization and transcription activities is complicated, such that it is difficult to decipher the regulatory effects of intranuclear geometrical cues. Here, we simplify the system by introducing DNA, packaging proteins (i.e., histone and protamine), and transcription factor NF-κB into a well-defined fluidic chip with changing spatical confinement ranging from 100 to 500 nm. It is uncovered that strong nanoconfinement suppresses higher-order folding of histone- and protamine-DNA complexes, the fracture of which exposes buried DNA segments and causes increased quantities of NF-κB binding to the DNA chain. Overall, these results reveal a pathway of how intranuclear geometrical cues alter the open/closed state of a DNA-protein complex and therefore affect transcription activities: i.e., NF-κB binding.

Predictive value of serum MDA and 4-HNE levels on the occurrence of early neurological deterioration after intravenous thrombolysis with rt-PA IVT in patients with acute ischemic stroke.

OBJECTIVE: This study investigated the predictive value of serum MDA and 4-HNE levels on early neurological deterioration (END) after recombinant tissue plasminogen activator (rt-PA) intravenous thrombolysis (IVT) in acute ischemic stroke (AIS) patients. METHODS: This study analyzed 287 AIS patients with standard-dose rt-PA IVT. Clinical baseline and pathological data were recorded before rt-PA IVT, and neurologic deficit was assessed by NIHSS. AIS patients were classified into Non-END and END groups. Serum MDA and 4-HNE levels were determined by ELISA and their correlations with NIHSS scores were evaluated. AIS patients were allocated into groups with high and low MDA or 4-HNE expression, and post-IVT END incidence was compared. Independent risk indexes for post-IVT END and the predictive value of serum MDA+4-HNE levels on post-IVT END were assessed. RESULTS: Serum MDA and 4-HNE were higher in AIS patients with post-IVT END. NIHSS score showed a positive correlation with serum MDA and 4-HNE levels. MDA levels were positively correlated with 4-HNE levels in AIS patients. END after IVT was increased in AIS patients with high MDA/4-HNE expression. FBG, lymphocyte percentage, PLR, NIHSS score, serum MDA, and 4-HNE levels were independent risk factors for END after IVT. The diagnostic efficacy of MDA+4-HNE in assessing post-IVT END in AIS patients (sensitivity 92.00 %, specificity 82.70 %) was higher than MDA or 4-HNE alone. CONCLUSION: Serum MDA and 4-HNE levels were higher in AIS patients with post-IVT END than in those with non-END, and MDA+4-HNE possessed a higher predictive value for post-IVT END in AIS patients.

Effect of ozone sterilization on controlling leaf mildew and gray mold tomato disease in a glasshouse and its influence on other growth parameters.

BACKGROUND: In order to explore the effect of ozone sterilization treatment on tomato disease control and increase fruit setting rate, this study took 906 pink fruit tomato as test material, used a small ozone generator to carry out ozone treatment single-factor test, and then selected orthogonal table to guide the ozone treatment combination. The effects of different ozone treatment concentration, ozone treatment duration and ozone treatment times on the growth, disease and fruit setting rate of potted tomato were analyzed. RESULTS: Different ozone treatment had effects on leaf mildew, gray mold and fruit setting rate of tomato. The influence degree of three factors on leaf mildew, gray mold and fruit setting rate was from large to small, a > b > c, a > c > b, b > a > c. A quadratic regression model was established with the control effect of tomato leaf mildew, gray mold and fruit setting rate as response values, and the optimal parameter combination was determined: The ozone treatment concentration was 0.0465 g kg-1, the ozone treatment time was 30 min, and the ozone treatment times were twice a week. In this case, the control efficiency of tomato leaf mildew was 95.02%, the control effect of gray mold was 99.49%, and the fruit setting rate was 76.5%. The test parameters were accurate and reliable. CONCLUSION: The ozone sterilization method proposed in this article is safe and green, and can provide theoretical support for the recovery and reconstruction of tomato disease in a glasshouse. © 2024 Society of Chemical Industry.

Transmembrane serine protease TMPRSS2 implicated in SARS-CoV-2 infection is autoactivated intracellularly and requires N-glycosylation for regulation.

Transmembrane protease serine 2 (TMPRSS2) is a membrane-bound protease expressed in many human epithelial tissues, including the airway and lung. TMPRSS2-mediated cleavage of viral spike protein is a key mechanism in severe acute respiratory syndrome coronavirus 2 activation and host cell entry. To date, the cellular mechanisms that regulate TMPRSS2 activity and cell surface expression are not fully characterized. In this study, we examined two major post-translational events, zymogen activation and N-glycosylation, in human TMPRSS2. In experiments with human embryonic kidney 293, bronchial epithelial 16HBE, and lung alveolar epithelial A549 cells, we found that TMPRSS2 was activated via intracellular autocatalysis and that this process was blocked in the presence of hepatocyte growth factor activator inhibitors 1 and 2. By glycosidase digestion and site-directed mutagenesis, we showed that human TMPRSS2 was N-glycosylated. N-glycosylation at an evolutionarily conserved site in the scavenger receptor cysteine-rich domain was required for calnexin-assisted protein folding in the endoplasmic reticulum and subsequent intracellular trafficking, zymogen activation, and cell surface expression. Moreover, we showed that TMPRSS2 cleaved severe acute respiratory syndrome coronavirus 2 spike protein intracellularly in human embryonic kidney 293 cells. These results provide new insights into the cellular mechanism in regulating TMPRSS2 biosynthesis and function. Our findings should help to understand the role of TMPRSS2 in major respiratory viral diseases.

Odor Enrichment Attenuates the Anesthesia/Surgery-induced Cognitive Impairment.

OBJECTIVE: To determine the association between olfactory function and cognition in patients and rodents. BACKGROUND: Perioperative neurocognitive disorders include delayed neurocognitive recovery (dNCR). The contribution of olfactory function to dNCR remains undetermined. It is unknown whether odor enrichment could mitigate dNCR. METHODS: We performed a prospective observational cohort study to determine potential association between olfactory impairment and dNCR in patients. We assessed the effects of anesthesia/surgery on olfactory and cognitive function in mice using the block test and Barnes maze. We measured interleukin-6 (IL-6), olfactory mature protein, growth-associated protein 43, mature and premature olfactory neurons, postsynaptic density 95, and synaptophysin in blood, nasal epithelium, and hippocampus of mice. Odor enrichment, IL-6 antibody, and knockout of IL-6 were used in the interaction experiments. RESULTS: Patients with dNCR had worse odor identification than the patients without dNCR [preoperative: 7 (1.25, 9) vs 10 (8, 11), median (interquartile range), P <0.001; postoperative: 8 (2.25, 10) vs 10 (8, 11), P <0.001]. Olfactory impairment associated with dNCR in patients before and after adjusting age, sex, education, preoperative mini-mental state examination score, and days of the neuropsychological tests. Anesthesia/surgery induced olfactory and cognitive impairment, increased levels of IL-6 in blood and nasal epithelium, decreased amounts of olfactory receptor neurons and their markers in the nasal epithelium, and reduced amounts of synapse markers in the hippocampus of mice. These changes were attenuated by odor enrichment and IL-6 antibody. CONCLUSION: The anesthesia/surgery-induced olfactory impairment may contribute to dNCR in patients and postoperative cognitive impairment in mice. Odor enrichment could be a potential intervention.

Activation of endogenous retrovirus triggers microglial immuno-inflammation and contributes to negative emotional behaviors in mice with chronic stress.

BACKGROUND: The "missing" link of complex and multifaceted interplay among endogenous retroviruses (ERVs) transcription, chronic immuno-inflammation, and the development of psychiatric disorders is still far from being completely clarified. The present study was aimed to investigate the mechanism of protective role of inhibiting ERVs on reversing microglial immuno-inflammation in basolateral amygdala (BLA) in chronic stress-induced negative emotional behaviors in mice. METHODS: Male C57BL/6 mice were exposed to chronic unpredictable mild stress (CUMS) for 6 w. Negative emotional behaviors were comprehensively investigated to identify the susceptible mice. Microglial morphology, ERVs transcription, intrinsic nucleic acids sensing response, and immuno-inflammation in BLA were assessed. RESULTS: Mice with chronic stress were presented as obviously depressive- and anxiety-like behaviors, and accompanied with significant microglial morphological activation, murine ERVs genes MuERV-L, MusD, and IAP transcription, cGAS-IFI16-STING pathway activation, NF-κB signaling pathway priming, as well as NLRP3 inflammasome activation in BLA. Antiretroviral therapy, pharmacological inhibition of reverse transcriptases, as well as knocking-down the ERVs transcriptional regulation gene p53 significantly inhibited microglial ERVs transcription and immuno-inflammation in BLA, as well as improved the chronic stress-induced negative emotional behaviors. CONCLUSIONS: Our results provided an innovative therapeutic approach that targeting ERVs-associated microglial immuno-inflammation may be beneficial to the patients with psychotic disorders.

Programmable Microfluidics Enabled by 3D Printed Bionic Janus Porous Matrics for Microfluidic Logic Chips.

Numerous structures have been functionally optimized for directional liquid transport in nature. Inspired by lush trees' xylem that enable liquid directional transportation from rhizomes to the tip of trees, a new kind of programmable microfluidic porous matrices using projection micro-stereolithography (PµSL) based 3D printing technique is fabricated. Structural matrices with internal superhydrophilicity and external hydrophobicity are assembled for ultra-fast liquid rising enabled by capillary force. Moreover, the unidirectional microfluidic performance of the bionic porous matrices can be theoretically optimized by adjusting its geometric parameters. Most significantly, the successive programmable flow of liquid in a preferred direction inside the bionic porous matrices with tailored wettability is achieved, validating by a precisely printed liquid displayer and a microfluidic logic chip. The programmable and functional microfluidic matrices promise applications of patterned liquid flow, displayer, logic chip, cell screening, gas-liquid separation, and so on.

An elevated triglyceride-glucose index predicts adverse outcomes and interacts with the treatment strategy in patients with three-vessel disease.

BACKGROUND: Insulin resistance is a pivotal risk factor for cardiovascular diseases, and the triglyceride-glucose (TyG) index is a well-established surrogate of insulin resistance. This study aimed to investigate the prognostic value of the TyG index and its ability in therapy guidance in patients with three-vessel disease (TVD). METHODS: A total of 8862 patients with TVD with available baseline TyG index data were included in the study. The endpoint was major adverse cardiac events (MACE). All patients received coronary artery bypass grafting (CABG), percutaneous coronary intervention (PCI), or medical therapy (MT) alone reasonably. RESULTS: An elevated TyG index was defined as the TyG index greater than 9.51. During a median follow-up of 7.5 years, an elevated TyG index was significantly associated with an increased risk of MACE (adjusted hazard ratio 1.161, 95% confidence interval 1.026-1.314, p = 0.018). The elevated TyG index was shown to have a more pronounced predictive value for MACE in patients with diabetes, but failed to predict MACE among those without diabetes, whether they presented with stable angina pectoris (SAP) or acute coronary syndrome (ACS). Meanwhile, the association between an elevated TyG index and MACE was also found in patients with left main involvement. Notably, CABG conferred a significant survival advantage over PCI in patients with a normal TyG index, but was not observed to be superior to PCI in patients with an elevated TyG index unless the patients had both ACS and diabetes. In addition, the benefit was shown to be similar between MT and revascularisation among patients with SAP and an elevated TyG index. CONCLUSIONS: The TyG index is a potential indicator for risk stratification and therapeutic decision-making in patients with TVD.

CCL6 promotes M2 polarization and inhibits macrophage autophagy by activating PI3-kinase/Akt signalling pathway during skin wound healing.

The transition of macrophages from the proinflammatory M1 to the anti-inflammatory M2 phenotype is crucial during the wound healing process. In this study, we assess the role of chemokine (C-C motif) ligand 6 (CCL6) in modulating macrophage polarization and wound healing. Initially, we observed significantly upregulated CCL6 expression in the skin tissue on the edge of the wound during the inflammation and proliferation phases. Furthermore, we discovered that the mice treated with rCCL6 had significantly accelerated wound healing and increased levels of M2-type macrophages. Using in vitro models, we found that CCL6 promotes the M2 polarization of macrophages by activating the PI3-kinase/Akt signalling pathway. Additionally, our results showed that CCL6 inhibited macrophage autophagy and accelerated wound healing, whereas the autophagy inducer rapamycin delayed wound healing. Finally, we determined that the PI3-kinase inhibitor LY294002 promoted macrophage autophagy and decreased M2 macrophages, indicating the importance of PI3-kinase in M2 polarization, and this process was reversed by CCL6. Taken together, our study demonstrates that CCL6 promotes M2 polarization, inhibits macrophage autophagy, and accelerates skin wound healing by activating the PI3-kinase/Akt signalling pathway.

Relationship between plasma amino acid and carnitine levels and primary angle-closure glaucoma based on mass spectrometry metabolomics.

World blindness is primarily caused by glaucoma. It has been predicted that by 2040, 118 million individuals will have glaucoma. Among Asians and Africans, primary angle-closure glaucoma (PACG) is the most prevalent type of glaucoma, for which treatment options are currently very limited. At present, lowering intraocular pressure (IOP) is the primary approach for PACG treatment. However, some PACG patients with decreased IOP measurements still advance. Additionally, because of the complicated pathophysiology, there are no biomarkers for diagnosis. Metabolomics is the study of the metabolites produced by all cellular processes in a biological sample, providing a method for identifying biomarkers and early diagnosis. Nevertheless, metabolomics has infrequently been applied to PACG. Previous research conducted by our lab on plasma metabolite fatty acids in PACG patients revealed reduced free fatty acid (FFA) levels, which may be connected to lipid peroxidation. To ascertain the relationship between other metabolites and PACG. We compared levels of amino acids and carnitine in patients with PACG (n = 147) and non-glaucoma (n = 340). Using metabolomics analysis, twenty-one amino acids and twenty-six carnitines (a total of ninety-six indicators) were examined. Odds ratios (OR) and 95% confidence intervals (CI) for these metabolites in relation to PACG were calculated. The relationship between ocular measures and metabolites was assessed by Spearman's rank correlation. Predictive performance was evaluated using the receiver operating characteristic (ROC). The C8/C2 level was comparable across patients with PACG and individuals without glaucoma based on the Wilcoxon rank-sum test. The PACG group had lower levels of Arginine (Arg), Ornithine (Orn), Arg/Orn, Orn/Cit, and C26/C20 than the nonglaucoma group, whereas Cit/Arg and C4/C2 ratios were greater. Both univariate and multivariate models showed a negative correlation between Orn and Orn/Cit and PACG. In the univariate model, palmitoylcarnitine (C16) had a negative correlation with PACG. According to our findings, metabolic profiles of plasma amino acids and carnitine between PACG patients and controls are different. The combination of amino acids and carnitine increased the predictive value of PACG. The Orn and Arg were negatively correlated with the local ocular neurodegenerative pathology. We speculate lipid peroxidation may explain the reduction in C16, and the decrease in Orn may be associated with hyperammonia neurotoxicity.

TRIM29 promotes podocyte pyroptosis in diabetic nephropathy through the NF-kB/NLRP3 inflammasome pathway.

Diabetic nephropathy (DN) is one of the most common complications of diabetes. Gradual loss of podocytes is a sign of DN and pyroptosis mechanistically correlates with podocyte injury in DN; however, the mechanism(s) involved remain unknown. Here we reveal that TRIM29 is overexpressed in high glucose (HG)-treated murine podocytes cells and that TRIM29 silencing significantly inhibits podocyte damage due to HG treatment, as evidenced by lower desmin expression and greater nephrin expression. Additionally, flow cytometry analysis showed that TRIM29 silencing significantly inhibited HG treatment-induced pyroptosis, which was confirmed by immunoblotting for NLRP3, active Caspase-1, GSDMD-N, and phosphorylated NF-κB-p65. Conversely, overexpression of TRIM29 could trigger pyroptosis that was attenuated by NF-κB inhibition, indicating that TRIM29 promotes pyroptosis through the NF-κB pathway. Mechanistic studies revealed that TRIM29 interacts with IκBα to mediate its ubiquitination-dependent degradation, which in turn leads to NF-κB activation. Taken together, our data demonstrate that TRIM29 can promote podocyte pyroptosis by activating the NF-κB/NLRP3 pathway. Thus, TRIM29 represents a potentially novel therapeutic target that may also be clinically relevant in the management of DN.

Latencies to the first interictal epileptiform discharges recorded by the electroencephalography in different epileptic patients.

PURPOSE: Interictal epileptiform discharges (IEDs) captured in electroencephalography (EEG) have a high diagnostic value for epileptic patients. Extending the recording time may increase the possibility of obtaining IEDs. The purpose of our research was to determine how long it took for various epileptic individuals to receive their first IEDs. METHODS: We retrospectively analyzed patients who were diagnosed with epilepsy and had no anti-seizure medications (ASMs) between September 2018 and March 2019 in the neurology department of the First Affiliated Hospital of Xi'an Jiaotong University. Each individual underwent a 24-h long-term video electroencephalographic monitoring (VEM) procedure. Clinical information including age, gender, age of seizure onset, frequency of seizures, the interval between last seizure and VEM, and results of neuroimaging were gathered. We also calculated the times from the start of the VEM to the first definite IEDs. RESULTS: A total of 241 patients were examined, including 191 with focal-onset epilepsy and 50 with generalized epilepsy. In individuals with focal-onset epilepsy, the median latency to the first IED was 63.0 min (IQR 19.0-299.0 min), as compared to 30.0 min (IQR 12.5-62.0 min) in patients with generalized epilepsy (p < 0.001). The latency to the first IED is significantly related to the age of seizure onset (HR = 0.988, p = 0.049), the interval between last seizure and VEM (HR = 0.998, p = 0.013). But it is not correlated with seizure frequency, gender and age. CONCLUSIONS: IEDs were discovered during 24-h EEG monitoring in 222/241(92.1%) of the epilepsy patients that were included. Compared to focal-onset epilepsy, generalized epilepsy demonstrated a much shorter latency to IED. Patients with late-onset epilepsy or those without recent episodes may require longer EEG monitoring periods.

Krüppel-like factor 17 upregulates uterine corin expression and promotes spiral artery remodeling in pregnancy.

Spiral artery remodeling is an important physiological process in the pregnant uterus which increases blood flow to the fetus. Impaired spiral artery remodeling contributes to preeclampsia, a major disease in pregnancy. Corin, a transmembrane serine protease, is up-regulated in the pregnant uterus to promote spiral artery remodeling. To date, the mechanism underlying uterine corin up-regulation remains unknown. Here we show that Krüppel-like factor (KLF) 17 is a key transcription factor for uterine corin expression in pregnancy. In cultured human uterine endometrial cells, KLF17 binds to the CORIN promoter and enhances the promoter activity. Disruption of the KLF17 gene in the endometrial cells abolishes CORIN expression. In mice, Klf17 is up-regulated in the pregnant uterus. Klf17 deficiency prevents uterine Corin expression in pregnancy. Moreover, Klf17-deficient mice have poorly remodeled uterine spiral arteries and develop gestational hypertension and proteinuria. Together, our results reveal an important function of KLF17 in regulating Corin expression and uterine physiology in pregnancy.

Neuroglobin protects against cerebral ischemia/reperfusion injury in rats by suppressing mitochondrial dysfunction and endoplasmic reticulum stress-mediated neuronal apoptosis through synaptotagmin-1.

Cerebral ischemia/reperfusion (I/R) injury remains a grievous health threat, and herein effective therapy is urgently needed. This study explored the protection of neuroglobin (Ngb) in rats with cerebral I/R injury. The focal cerebral I/R rat models were established by middle cerebral artery occlusion (MCAO) and neuronal injury models were established by oxygen-glucose deprivation/reoxygenation (OGD/R) treatment. The brain injury of rats was assessed. Levels of Ngb, Bcl-2, Bax, endoplasmic reticulum stress (ERS)-related markers, and Syt1 were measured by immunofluorescence staining and Western blotting. The cytotoxicity in neurons was assessed by lactate dehydrogenase (LDH) release assay. Levels of intracellular Ca2+ and mitochondrial function-related indicators were determined. The binding between Ngb and Syt1 was detected by co-immunoprecipitation. Ngb was upregulated in cerebral I/R rats and its overexpression alleviated brain injury. In OGD/R-induced neurons, Ngb overexpression decreased LDH level and neuronal apoptosis, decreased Ca2+ content, and mitigated mitochondrial dysfunction and ERS-related apoptosis. However, Ngb silencing imposed the opposite effects. Importantly, Ngb could bind to Syt1. Syt1 knockdown partially counteracted the alleviation of Ngb on OGD/R-induced injury in neurons and cerebral I/R injury in rats. Briefly, Ngb extenuated cerebral I/R injury by repressing mitochondrial dysfunction and endoplasmic reticulum stress-mediated neuronal apoptosis through Syt1.

Biomechanical Load of Neck and Lumbar Joints in Open-Surgery Training.

The prevalence of musculoskeletal symptoms (MSS) like neck and back pain is high among open-surgery surgeons. Prolonged working in the same posture and unfavourable postures are biomechanical risk factors for developing MSS. Ergonomic devices such as exoskeletons are possible solutions that can reduce muscle and joint load. To design effective exoskeletons for surgeons, one needs to quantify which neck and trunk postures are seen and how much support during actual surgery is required. Hence, this study aimed to establish the biomechanical profile of neck and trunk postures and neck and lumbar joint loads during open surgery (training). Eight surgical trainees volunteered to participate in this research. Neck and trunk segment orientations were recorded using an inertial measurement unit (IMU) system during open surgery (training). Neck and lumbar joint kinematics, joint moments and compression forces were computed using OpenSim modelling software and a musculoskeletal model. Histograms were used to illustrate the joint angle and load distribution of the neck and lumbar joints over time. During open surgery, the neck flexion angle was 71.6% of the total duration in the range of 10~40 degrees, and lumbar flexion was 68.9% of the duration in the range of 10~30 degrees. The normalized neck and lumbar flexion moments were 53.8% and 35.5% of the time in the range of 0.04~0.06 Nm/kg and 0.4~0.6 Nm/kg, respectively. Furthermore, the neck and lumbar compression forces were 32.9% and 38.2% of the time in the range of 2.0~2.5 N/kg and 15~20 N/kg, respectively. In contrast to exoskeletons used for heavy lifting tasks, exoskeletons designed for surgeons exhibit lower support torque requirements while additional degrees of freedom (DOF) are needed to accommodate combinations of neck and trunk postures.

miR-221 promotes keratinocyte proliferation and migration by targeting SOCS7 and is regulated by YB-1.

Proliferation and migration of keratinocytes are vital processes for the successful epithelization specifically after wounding. MiR-221 has been identified to play a potential role in promoting wound regeneration by inducing blood vessel formation. However, little is known about the role of miR-221 in the keratinocyte proliferation and migration during wound healing. An in vivo mice wound-healing model was generated; the expression levels of miR-221 were assessed by qRT-PCR and fluorescence in situ hybridization. Initially, we found that miR-221 was upregulated in the proliferative phase of wound healing. Further, in an in vivo wound-healing mice model, targeted delivery of miR-221 mimics accelerated wound healing. Contrastingly, inhibition of miR-221 delayed healing. Additionally, we observed that overexpression of miR-221 promoted cell proliferation and migration, while inhibition of miR-221 had the opposite effects. Moreover, we identified SOCS7 as a direct target of miR-221 in keratinocytes and overexpression of SOCS7 reversed the effects of miR-221 in HaCaT keratinocytes. Finally, we identified that YB-1 regulates the expression of miR-221 in HaCaT keratinocytes. Overall, our experiments suggest that miR-221 is regulated by YB-1 in HaCaT keratinocytes and acts on SOCS7, thereby playing an important role in HaCaT keratinocyte proliferation and migration during wound healing.

High fibrinogen-to-albumin ratio with type 2 diabetes mellitus is associated with poor prognosis in patients undergoing percutaneous coronary intervention: 5-year findings from a large cohort.

BACKGROUND: Inflammation plays a crucial role in coronary atherosclerosis progression, and growing evidence has demonstrated that the fibrinogen-to-albumin ratio (FAR), as a novel inflammation biomarker, is associated with the severity of coronary artery disease (CAD). However, the long-term risk of cardiovascular events remains indistinct in patients with different level of FAR and different glycemic metabolism status. This study was to assess 5-year clinical outcomes of diabetic and non-diabetic patients who underwent percutaneous coronary intervention (PCI) with different level of FAR. METHODS: We consecutively enrolled 10,724 patients with CAD hospitalized for PCI and followed up for the major adverse cardiac and cerebrovascular events (MACCE) covering all-cause mortality, cardiac mortality, non-fatal myocardial infarction, non-fatal ischemic stroke, and unplanned coronary revascularization. FAR was computed using the following formula: Fibrinogen (g/L)/Albumin (g/L). According to the optimal cut-off value of FAR for MACCE prediction, patients were divided into higher level of FAR (FAR-H) and lower level of FAR (FAR-L) subgroups, and were further categorized into four groups as FAR-H with DM and non-DM, and FAR-L with DM and non-DM. RESULTS: 5298 patients (58.36 ± 10.36 years, 77.7% male) were ultimately enrolled in the present study. A total of 1099 (20.7%) MACCEs were documented during the 5-year follow-up. The optimal cut-off value of FAR was 0.0783 by the surv_cutpoint function. Compared to ones with FAR-H and DM, patients with FAR-L and non-DM, FAR-H and non-DM, FAR-L and DM had decreased risk of MACCEs [adjusted hazard ratio (HR): 0.75, 95% confidence interval (CI) 0.64-0.89, P = 0.001; HR: 0.78, 95% CI 0.66-0.93, P = 0.006; HR: 0.81, 95% CI 0.68-0.97, P = 0.019; respectively]. Notably, non-diabetic patients with lower level of FAR also had lower all-cause mortality and cardiac mortality risk than those in the FAR-H/DM group (HR: 0.41, 95% CI 0.27-0.63, P < 0.001; HR: 0.30, 95% CI 0.17-0.53, P < 0.001; respectively). Multivariate Cox proportional hazards regression analysis also indicated the highest risk of MACCEs in patients with FAR-H and DM than others (P for trend = 0.005). In addition, post-hoc analysis revealed consistent effects on 5-year MACCE across various subgroups. CONCLUSION: In this real-world cohort study, higher level of FAR combined with DM was associated with worse 5-year outcomes among patients with CAD undergoing PCI. The level of FAR may help to identify high-risk individuals in this specific population, where more precise risk assessment should be performed.

Airy theory revisited with the method combining vectorial complex ray model and physical optics.

Airy published his theory in the 1830s to remedy the problem of infinite intensity in the rainbow angles of a spherical droplet predicted by geometrical optics. This theory has been studied by mathematicians and physicists since then from different points of view. In what concerns the scattering diagram around the rainbow angles, Airy theory has been improved by researchers in order to predict correctly the intensity of the supernumerary bows. However, it is known that the positions and the intensities of the supernumerary bows predicted by Airy theory differ from those of rigorous Debye theory with increasing order p and the scattering angles from the rainbow angle. In the present Letter, we will show that this discrepancy is caused by the approximations in Airy theory and can be revised by combining the vectorial complex ray model and physical optics (PO). The former permits us to calculate rigorously the amplitudes and phases of all rays and predicts precisely the scattering pattern except for the main bows. The combination with PO predicts very precisely all the supernumerary bows for both perpendicular and parallel polarization. This method can be applied directly to the light scattering of non-spherical particles with smooth surfaces.