Genomic and Phenotypic Adaptations of Rattus tanezumi to Cold Limit Its Further Northward Expansion and Range Overlap with R. norvegicus.

Global climate change has led to shifts in the distribution ranges of many terrestrial species, promoting their migration from lower altitudes or latitudes to higher ones. Meanwhile, successful invaders have developed genetic adaptations enabling the colonization of new environments. Over the past 40 years, Rattus tanezumi (RT) has expanded into northern China (Northwest and North China) from its southern origins. We studied the cold adaptation of RT and its potential for northward expansion by comparing it with sympatric Rattus norvegicus (RN), which is well adapted to cold regions. Through population genomic analysis, we revealed that the invading RT rats have split into three distinct populations: the North, Northwest, and Tibetan populations. The first two populations exhibited high genetic diversity, while the latter population showed remarkably low genetic diversity. These rats have developed various genetic adaptations to cold, arid, hypoxic, and high-UV conditions. Cold acclimation tests revealed divergent thermoregulation between RT and RN. Specifically, RT exhibited higher brown adipose tissue activity and metabolic rates than did RN. Transcriptome analysis highlighted changes in genes regulating triglyceride catabolic processes in RT, including Apoa1 and Apoa4, which were upregulated, under selection and associated with local adaptation. In contrast, RN showed changes in carbohydrate metabolism genes. Despite the cold adaptation of RT, we observed genotypic and phenotypic constraints that may limit its ability to cope with severe low temperatures farther north. Consequently, it is less likely that RT rats will invade and overlap with RN rats in farther northern regions.

High-Energy SiO-Sulfur Battery with Preloaded Li3N in a Cathode as a Lithiation Reagent.

The practical use of lithium-sulfur batteries faces the "shuttle effect" and lithium dendrite growth. Employing SiO instead of Li metal can fundamentally solve the above problems. Nevertheless, selecting a convenient prelithiation method is essential for normal operation of the battery system. Hence, this work proposed a novel SiO-sulfur battery with preloaded Li3N in a cathode as a prelithiation reagent, which can thoroughly solve the dendrite problem and the side reaction with polysulfides of lithium anode. The S@KB-Li3N vs SiO full cell can obtain a high specific capacity of 790 mAh g-1 after the activation process and be maintained at 478 mAh g-1 after 100 cycles. Our design will provide a new prelithiation strategy for a high-specific-energy SiO-sulfur battery system.

Milk fat globule epidermal growth factor 8 alleviates liver injury in severe acute pancreatitis by restoring autophagy flux and inhibiting ferroptosis in hepatocytes.

BACKGROUND: Liver injury is common in severe acute pancreatitis (SAP). Excessive autophagy often leads to an imbalance of homeostasis in hepatocytes, which induces lipid peroxidation and mitochondrial iron deposition and ultimately leads to ferroptosis. Our previous study found that milk fat globule epidermal growth factor 8 (MFG-E8) alleviates acinar cell damage during SAP via binding to αvß3/5 integrins. MFG-E8 also seems to mitigate pancreatic fibrosis via inhibiting chaperone-mediated autophagy. AIM: To speculate whether MFG-E8 could also alleviate SAP induced liver injury by restoring the abnormal autophagy flux. METHODS: SAP was induced in mice by 2 hly intraperitoneal injections of 4.0 g/kg L-arginine or 7 hly injections of 50 µg/kg cerulein plus lipopolysaccharide. mfge8-knockout mice were used to study the effect of MFG-E8 deficiency on SAP-induced liver injury. Cilengitide, a specific αvß3/5 integrin inhibitor, was used to investigate the possible mechanism of MFG-E8. RESULTS: The results showed that MFG-E8 deficiency aggravated SAP-induced liver injury in mice, enhanced autophagy flux in hepatocyte, and worsened the degree of ferroptosis. Exogenous MFG-E8 reduced SAP-induced liver injury in a dose-dependent manner. Mechanistically, MFG-E8 mitigated excessive autophagy and inhibited ferroptosis in liver cells. Cilengitide abolished MFG-E8's beneficial effects in SAP-induced liver injury. CONCLUSION: MFG-E8 acts as an endogenous protective mediator in SAP-induced liver injury. MFG-E8 alleviates the excessive autophagy and inhibits ferroptosis in hepatocytes by binding to integrin αVß3/5.

The Reduced Gray Matter Volume and Functional Connectivity of the Cerebellum in Type 2 Diabetes Mellitus with High Insulin Resistance.

INTRODUCTION: Insulin resistance is widely thought to be a critical feature in type 2 diabetes mellitus (T2DM), and there is significant evidence indicating a higher abundance of insulin receptors in the human cerebellum than cerebrum. However, the specific structural or functional changes in the cerebellum related to T2DM remain unclear, and the association between cerebellar alterations, insulin resistance, cognition, and emotion is yet to be determined. METHODS: We investigated neuropsychological performance, and structural and functional changes in specific cerebellar subregions in 43 T2DM patients with high insulin resistance (T2DM-highIR), 72 T2DM patients with low insulin resistance (T2DM-lowIR), and 50 controls. Furthermore, the correlation and stepwise multiple linear regression analysis were performed. RESULTS: Compared to the controls, T2DM exhibited lower cognitive scores and higher depressive/anxious scores. Furthermore, T2DM-highIR patients showed reduced gray matter volume (GMV) in the right cerebellar lobules VIIb, Crus I/II, and T2DM showed reduced GMV in left lobules I-IV compared to controls. Additionally, functional connectivity decrease was observed between the right lobules I-V and orbital part of the superior frontal gyrus in T2DM-highIR compared to both T2DM-lowIR and controls. Notably, there were negative correlations between the GMV of the lobules VIIb, Crus I/II, and updated homeostatic model assessment of insulin resistance, and positive correlation with executive/visuospatial performance in T2DM patients. CONCLUSIONS: These results suggest that the cerebellar lobules VIIb, Crus I/II, represent vulnerable brain regions in the context of insulin resistance. Overall, this study offers new insights into the neuropathophysiological mechanisms of brain impairment in patients with T2DM.

Durable lithium-ion insertion/extraction and migration behavior of LiF-encapsulated cobalt-free lithium-rich manganese-based layered oxide cathode.

Lithium-rich manganese-based cathode has made a subject of intense scrutiny for scientists and application researchers due to their exceptional thermal stability, high specific capacity, high operating voltage, and cost-effectiveness. However, the inclusion of cobalt, as a crucial component in lithium-rich manganese-based cathode materials, has become a cause for concern due to its limited availability and non-renewable nature, which eventually limits the growth of the battery industry and increase costs. Considering the poor stability of cobalt-free cathode, this work proposes a coating strategy of LiF through a simple high-temperature melting method. Directly coating LiF on Li1.2Ni0.2Mn0.6O2 surface is found to be an effective way to protect the cathode material, decrease metal solubility, and inhibit irreversible phase transition processes, thus leading to an improved electrochemical performance. As a result, the battery employing LiF coated Li1.2Ni0.2Mn0.6O2 cathode can be stabilized over 280 cycles and maintain a capacity of 110 mAh g-1 at 1C. What's more, the mechanisms of ion insertion/extraction behavior and ion migration process are also studied systematically. This study will open the avenue to develop a high-energy battery system with cobalt-free cathode.

Alterations of Spontaneous Cortical and Subcortical Activity in Type 2 Diabetes Mellitus with and without Depression.

INTRODUCTION: Type 2 diabetes mellitus (T2DM) patients with depression have a higher risk of complications and mortality than T2DM without depression. However, the exact neuropathophysiological mechanism remains unclear. Consequently, the current study aimed to investigate the alteration of cortical and subcortical spontaneous neural activity in T2DM patients with and without depression. METHODS: The demographic data, clinical variables, neuropsychological tests, and functional and anatomical magnetic resonance imaging of depressed T2DM (n = 47) of non-depressed T2DM (n = 59) and healthy controls (n = 41) were collected and evaluated. The correlation analysis, stepwise multiple linear regression, and receiver operating characteristic curve were performed for further analysis. RESULTS: Abnormal neural activities in the bilateral posterior cingulate cortex (PCC) and hippocampus were observed in depressed and non-depressed T2DM and the right putamen of the depressed T2DM. Interestingly, the subcortical degree centrality (DC) of the right hippocampus and putamen were higher in depressed than non-depressed T2DM. Furthermore, the cortical amplitude of low-frequency fluctuation (ALFF) in PCC, subcortical DC in the putamen of depressed T2DM, and hippocampus of non-depressed T2DM was correlated with cognitive scores. In contrast, the cortical fractional ALFF in PCC of non-depressed T2DM was correlated with depression scores. CONCLUSIONS: The abnormalities of spontaneous cortical activity in PCC and subcortical activity in the hippocampus might represent the neurobiological feature of cerebral dysfunction in T2DM. Notably, the altered subcortical activity in the right putamen might mainly associate with negative emotion in T2DM, which could be a promising biomarker for recognizing early cerebral dysfunction in depressed T2DM. This study provided a novel insight into the neuropathophysiological mechanism of brain dysfunction in T2DM with and without depression.

Changes to intraocular pressure and its correlation with corneal diameter in infants aged from 0 to 36 months.

Objective: This study examines the distribution and development of intraocular pressure (IOP) in infants aged from 0 to 36 months and analyzes its correlation with corneal diameter. Methods: The study used a retrospective case analysis methodology. Healthy infants treated in the ophthalmology department of Hebei Children's Hospital from December 2012 to December 2020 were included in the study. Among these infants, 385 had their IOP measured, and 432 had their corneal diameters measured. Furthermore, information such as birth history, growth and development, IOP, and corneal diameter were collected. Their IOPs were measured with an iCare portable rebound tonometer when the child was awake and calm, and the corneal diameter was measured with a Castroviejo caliper under chloral hydrate sedation. The infants were divided into five groups according to age, and SPSS statistical software was used to analyze, compare, and correlate IOP and corneal diameter variations. Results: The mean IOP values of 0-1 month, 1-6 months, 6-12 months, 12-24 months and 24-36 months groups were 7.42 ± 1.92, 9.10 ± 2.85, 12.00 ± 3.15, 13.72 ± 3.09, and 15.14 ± 2.67 mmHg, respectively. The differences in IOP of the 0-1 month old infants and the 1-6 months old infants with the other three groups were statistically significant; the difference in IOP between the 6-12 months group and the 24-36 months group was statistically significant. In the studied groups, the horizontal corneal diameters were 9.78 ± 0.14, 10.50 ± 0.29, 10.86 ± 0.23, 11.38 ± 0.07, and 11.72 ± 0.04 mm, respectively, and the vertical diameters of the cornea were 9.28 ± 0.26, 10.07 ± 0.18, 10.28 ± 0.14, 10.56 ± 0.24, and 10.85 ± 0.03 mm, respectively. The differences in the vertical and horizontal diameters of the cornea among the groups were statistically significant. Conclusion: Infants' IOP and corneal diameter positively correlate with age, and they peak in the first 12 months.

A novel mutation of RPGR in a Chinese family with X-linked retinitis pigmentosa.

AIM: To identify potential mutations and elucidate the clinical findings of male patients and female carriers of X-linked retinitis pigmentosa (XLRP) in a Chinese family. METHODS: A four generation pedigree was collected that consisted of 20 individuals. Genomic DNA was extracted from peripheral blood, and then the target fragments were amplified by PCR and sequenced directly. In addition, all affected patients and female carriers underwent comprehensively ophthalmic evaluation. RESULTS: A novel mutation c.2865G>A p.W955X in RPGR gene was identified of this family, including four affected individuals and eight carriers. All male patients, aging from 7 to 31y, tended to have more various, even potentially deleterious clinical features of RP. At the same time, individuals with heterozygous mutations (carriers) manifested a wide spectrum of clinical features. Herein, only two male patients and three female carriers manifested pathological myopia (PM). Among the female carriers, half of subjects who harbor poor visual acuity suffered esotropia or exotropia. Additionally, 16.7% and 66.7% of carriers had abnormal electroretinogram (ERG) and fundus, respectively. CONCLUSION: In this study, a novel mutation of the RPGR gene is identified, which broadens the spectrum of RPGR mutations, and elaborates the relationship between genotype and phenotype.

Prolonging the lifetime of a compact multi-wire-layered secondary winding in the Tesla transformer.

A compact multi-wire-layered secondary winding for the Tesla transformer was proposed by Zhao et al. [Rev. Sci. Instrum. 88(5), 055112 (2017)]. The basic idea is to wind multiple layers of a metal wire around a polymeric base tube. However, the lifetime of this type of winding is only about 200 000 pulses, and thus it fails to meet the requirement of a lifetime of 1 × 106 pulses. In this study, two methods are developed to prolong the lifetime of this winding. One method involves replacing the original three-skin wire with a polytetrafluoroethylene (PTFE) wire. The results of small-scale experiments in different conditions show that the lifetime of the PTFE-covered copper wire is at least ten times longer than that of the three-skin wire. The other method involves improving the local structure of this winding. A strong mechanical stress is concentrated at the small end of the winding, and a highly intense electric field appears in this region, where both reduce the lifetime of the winding. Improving the local structure of the winding theoretically prolongs its lifetime by a factor of 4. Both methods were applied to the original secondary winding of a Tesla transformer and extended its theoretical lifetime by a factor of 40. The modified winding had a lifetime longer than 2 × 106 pulses without any traces of discharge. This is equivalent to a lifetime longer than that of the original winding by a factor of 10 and verifies the effectiveness of the proposed methods.

Cumulative oxygen deficit is a novel predictor for the timing of invasive mechanical ventilation in COVID-19 patients with respiratory distress.

BACKGROUND AND OBJECTIVES: The timing of invasive mechanical ventilation (IMV) is controversial in COVID-19 patients with acute respiratory hypoxemia. The study aimed to develop a novel predictor called cumulative oxygen deficit (COD) for the risk stratification. METHODS: The study was conducted in four designated hospitals for treating COVID-19 patients in Jingmen, Wuhan, from January to March 2020. COD was defined to account for both the magnitude and duration of hypoxemia. A higher value of COD indicated more oxygen deficit. The predictive performance of COD was calculated in multivariable Cox regression models. RESULTS: A number of 111 patients including 80 in the non-IMV group and 31 in the IMV group were included. Patients with IMV had substantially lower PaO2 (62 (49, 89) vs. 90.5 (68, 125.25) mmHg; p < 0.001), and higher COD (-6.87 (-29.36, 52.38) vs. -231.68 (-1040.78, 119.83) mmHg·day) than patients without IMV. As compared to patients with COD < 0, patients with COD > 30 mmHg·day had higher risk of fatality (HR: 3.79, 95% CI [2.57-16.93]; p = 0.037), and those with COD > 50 mmHg·day were 10 times more likely to die (HR: 10.45, 95% CI [1.28-85.37]; p = 0.029). CONCLUSIONS: The study developed a novel predictor COD which considered both magnitude and duration of hypoxemia, to assist risk stratification of COVID-19 patients with acute respiratory distress.

Shp2 positively regulates cigarette smoke-induced epithelial mesenchymal transition by mediating MMP-9 production.

Cigarette smoke (CS) is a major risk factor for the development of lung cancer and chronic obstructive pulmonary disease (COPD). Epithelial-mesenchymal transition (EMT) commonly coexists in lung cancer and COPD. CS triggers many factors including matrix metalloproteinases (MMPs) production, contributing to EMT progression in the lungs. Here, how Shp2 signaling regulates the CS-induced MMP-9 production and EMT progression were investigated in mouse lungs and in pulmonary epithelial cell cultures (NCI-H292) found CS induced MMP-9 production, EMT progression (increased vimentin and α-SMA; decreased E-cadherin) and collagen deposition in lung tissues; cigarette smoke extract (CSE) induced MMP-9 production and EMT-related phenotypes in NCI-H292 cells, which were partially prevented by Shp2 KO/KD or Shp2 inhibition. The CSE exposure induced EMT phenotypes were suppressed by MMP-9 inhibition. Recombinant MMP-9 induced EMT, which was prevented by MMP-9 inhibition or Shp2 KD/inhibition. Mechanistically, CS and CSE exposure resulted in ERK1/2, JNK and Smad2/3 phosphorylation, which were suppressed by Shp2 KO/KD/inhibition. Consequentially, the CSE exposure-induced MMP-9 production and EMT progression were suppressed by ERK1/2, JNK and Smad2/3 inhibitors. Thus, CS induced MMP-9 production and EMT resulted from activation of Shp2/ERK1/2/JNK/Smad2/3 signaling pathways. Our study contributes to the underlying mechanisms of pulmonary epithelial structural changes in response to CS, which may provide novel therapeutic solutions for treating associated diseases, such as COPD and lung cancer.

A rapid response team is associated with reduced overall hospital mortality in a Chinese tertiary hospital: a 9-year cohort study.

BACKGROUND: Although the evidence for its effectiveness remains uncertainty, rapid response systems are implemented across many hospitals across the world. Increasingly, hospitals in China have recently started to adopt a medical emergency or rapid response team (RRT). Hence, we aimed to determine whether the implementation of an RRT in Chinese hospitals also improved outcomes. METHODS: Our hospital is a Joint Commission International (JCI) accredited, tertiary teaching hospital with 1,200 beds. We conducted a retrospective cohort study comparing 60 months after the implementation of the RRT (January 1, 2013, to December 31, 2017) and 36 months before implementation (January 1, 2009, to December 31, 2011). The outcomes included the overall hospital mortality and incidence of codes. RESULTS: We analyzed 144,673 non-obstetric hospital admissions and 1,269,621 patient days in the control period and 348,687 non-obstetric hospital admissions and 2,361,913 patient days after the RRT implementation. The RRT was activated 834 times (2.39 calls per 1,000 patients and 0.35 call per 1,000 patient-days). There was no difference in the code rate (0.23 vs. 0.17 per 1,000 patient days, P=0.379) between the two periods. Although the hospital mortality had remained stable around 3.0 per 1,000 patients from 2009 to 2011, there was a significant 40% decrease of overall hospital mortality from 2.95 to 1.77 per 1,000 non-obstetric patients after the implementation of RRT (P=0.001), and the annual mortality showed a consistent decrease (P=0.037 for the trend). Moreover, the increase of RRT activations was significantly correlated with the decrease of hospital mortality (P=0.025). CONCLUSIONS: RRT implementation was associated with reduced overall hospital mortality in a Chinese tertiary hospital.

Factors associated with outcomes of septic shock patients receiving high dose noradrenaline according to three primary infection sites.

OBJECTIVE: To identify factors associated with outcome of septic shock patients receiving high dose noradrenaline according to three primary infection sites. METHODS: This retrospective study was based on data from a publicly available ICU database (Medical Information Mart for Intensive Care [MIMIC] III. Septic shock patients receiving high dose (≥1 µg/kg per min) noradrenaline and ≥18 years were identified and their characteristics and outcomes were compared according to three primary infection sites (abdominal, respiratory and urinary tract). RESULTS: 154 septic shock patients who received high doses of noradrenaline were identified; (89 [58%] had a respiratory infection, 41 [27%] an abdominal infection and 24 [16%] a urinary infection). There were no differences among the three infection groups in duration/maximum dosage of noradrenaline, length of stay in the ICU/hospital, do not resuscitate (DNR) rates, hypertension and adequate antimicrobial therapy. Patients with urinary infections had a lower risk of death at 28-days compared with those with abdominal or respiratory infections. CONCLUSIONS: The prognosis for septic shock patients receiving high dose noradrenaline is poor. Patients with abdominal or respiratory infections are at higher risk of death compared with those with urinary infections.

Utilization of echocardiography during septic shock was associated with a decreased 28-day mortality: a propensity score-matched analysis of the MIMIC-III database.

BACKGROUND: Hemodynamic management is of paramount importance in patients with septic shock. Echocardiography has been increasingly used in assessing volume status and cardiac function. However, whether the utilization of echocardiography has an impact on prognosis is unknown. Thus, we intended to explore its effect on the outcomes of patients with septic shock. METHODS: The study was based on the Medical Information Mart for Intensive Care (MIMIC) III database. Septic shock patients were divided into two groups according to the usage of echocardiography during the onset of septic shock. The primary outcome was 28-day mortality. Secondary outcomes included the usage of inotropes, ventilation-free and norepinephrine-free time, and fluids input. Propensity-score matching was used to reduce the imbalance. RESULTS: Among 3,291 eligible patients, 1,289 patients who underwent echocardiography (Echo), and 1,289 who did not receive the Echo, had similar propensity scores and were included in the analyses. After matching, the Echo group had a significantly lower 28-day mortality (33.2% vs. 37.7%, P=0.019). More patients in the Echo group received pulmonary artery catheter (PAC) (4.2% vs. 0.2%, P<0.001) and inotropes (17.8% vs. 7.1%, P<0.001). In the survival analysis, Echo utilization was associated with improved 28-day mortality [hazard ratio (HR): 0.83; 95% confidence interval (CI), 0.73-0.95, P=0.005]. A reduced likelihood of 28-day mortality in patients with Echo vs. those without Echo was maintained either when excluding patients receiving multiple echocardiography scans (HR, 0.82; 95% CI, 0.72-0.94; P=0.004) or when excluding patients undergoing PAC or pulse index continuous cardiac output (PiCCO) (HR, 0.87; 95% CI, 0.76-0.99; P=0.034). CONCLUSIONS: Utilization of echocardiography was associated with improved 28-day outcomes in patients with septic shock.

A quasi-coaxial HV rolled pulse forming line.

A quasi-coaxial high-voltage (HV) rolled pulse forming line (rolled PFL) is researched in this paper. The PFL is rolled n circles on a support cylinder simultaneously by two layers of copper foil electrodes and two layers of insulation dielectrics. The first circle of the two electrodes are elicited in opposite directions along the axis, acting as the quasi-coaxial output structure of the PFL, and the left n - 1 circles of the PFL form a complete rolled strip line of n - 1 circles. The rolled PFL is convenient to realize HV insulation and is able to output a pulse with good quality. Characteristic parameters of the PFL are designed theoretically. Besides, the pulse discharge process of the PFL is simulated by computer simulation technology (CST) modeling, and the simulation result verifies the correctness of theory design. Furthermore, a rolled PFL with a characteristic impedance of 4.4 Ω is developed. The test characteristic impedance of the developed PFL by the incident pulse method confirms to the theory design. The discharge voltage waveform with a full width at half maximum of 57 ns of the PFL is acquired, which has a rise time of 6.8 ns. The HV test of the rolled PFL is carried out, and a discharge current pulse with an amplitude of 7 kA is acquired when the PFL is charged to 70 kV. It is calculated that the developed PFL has an energy storage density of 2.5 J/l. A Tesla generator based on 13 stages of rolled PFLs is designed, which is expected to output a 450 kV pulse with a duration of 100 ns on a 40-Ω match load. The discharge waveform of the generator is simulated by the CST software. The simulative output pulse has a rise time of 5 ns, with a flattop jitter less than 5%.