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Surveys and research on the applications of the hepatic venous pressure gradient (HVPG) are important for understanding the current status and future development of this technology in China. This article aimed to investigate the status of hepatic venous pressure gradient measurement in China in 2022. We investigated the overall status of HVPG technology in China—including hospital distribution, hospital level, annual number of cases, catheters used, average cost, indications, and current challenges by using online questionnaire. By counting the number and percentages of cases of these results, we hope to clarify the current status of HVPG measurements in China. According to the survey, 85 hospitals in China used HVPG technology in 2022 distributed across 29 provinces. A total of 4989 HVPG measurements were performed in all of the surveyed hospitals in 2022, of which 2813 cases (56.4%) were measured alone. The average cost of HVPG measurement was 5646.8 ± 2327.9 CNY. Of the clinical teams who performed the measurements (sometimes multiple per hospital), 94.3% (82/87) used the balloon method, and the majority of the teams (72.4%, 63/87) used embolectomy catheters. This survey clarified the clinical application status of HVPG in China and confirmed that some medical institutions in China have established a foundation for this technology. It is still necessary to continue promoting and popularizing this technology in the future. A survey analysis of hepatic venous pressure gradient for portal hypertension in China. Significant findings of the study Some medical institutions in China have already mastered the technique and applied it in their clinical practices. However, promoting and popularizing hepatic venous pressure gradient (HVPG) is still necessary. What this study adds We analyzed the overall status of HVPG measurement technology in China.

A new ultrafast interrogation is proposed based on the peanut shaped tapered fiber (PSTF) interference structure and time-stretching method. The single mode fiber (SMF) is tapered by tapering machine to achieve a minimum core diameter width of 10.86 μm. Thanks to the peanut structure as a beam expander and collector, multiple high order modes have been excited. The interference between core mode and cladding modes has a high response to changes in surrounding salinity, with a salinity sensitivity of 0.302 nm/‰ and a corresponding refractive index (RI) sensitivity of up to 1800.535 nm/RIU. The time-stretching method is put forward and experimentally demonstrated. Once the femtosecond light pulse is modulated by the PSTF interferometer, the pulse light carrying information is transmitted to a dispersion compensation fiber (DCF) to achieve wavelength to time mapping and the spectrum in the time domain can be directly collected on an oscilloscope (OSC). By monitoring the time shift of salinity modifications, a salinity sensitivity of −0.128 ns/‰ and a real-time acquisition speed of 50 MHz for the sensing system is realized. The proposed salinity monitoring system has the advantages of high sensitivity, fast response speed, low cost and high accuracy. It has significant potential for real-time monitoring and timely provision of salinity data, which can help improve water quality and achieve scientific aquaculture. The proposed interrogation technology has broad application prospects for any real-time monitoring based on fiber optic interference modulation.

Byline: Yingtian. Wei, Yueyong. Xiao, Zhongmin. Wang, Xiaokun. Hu, Guang. Chen, Xiaoyi. Ding, Yong. Fan, Yue. Han, Kaiwen. Huang, Xuequan. Huang, Ming. Kuang, Xu. Lang, Hailiang. Li, Chengli. Li, Jiakai. [...]

The transjugular intrahepatic portosystemic shunt (TIPS) procedure has been performed in China for 30 years, but our understanding of the status and difficulties associated with the use of TIPS for portal hypertension is incomplete. This study aims to investigate the current situation of the use of TIPS for portal hypertension, which should aid the development of TIPS in China. This study involved a questionnaire survey, initiated by the China Portal Hypertension Alliance (CHESS) to investigate the use of TIPS for portal hypertension in China. Questionnaires were released on the Internet between August 16, 2022 and September 16, 2022. Detailed information was collected from 545 hospitals contracted by the CHESS in China, which performed TIPS surgery in 2021. The 545 hospitals covers the majority of hospitals in China that conduct TIPS intervention. In the survey, a total of 13,527 TIPS interventions were carried out with 94.1% (498/545) of them had a system of routine follow‐up after TIPS. The majority (42.6% [232/545]) believed that the main indication of TIPS was the control of acute bleeding. Overall, 48.1% (262/545) carried out early or pre‐emptive TIPS, 53.0% (289/545) carried out TIPS for cavernous transformation of the portal vein, and 81.0% (441/545) chose routine embolization of collateral circulation during operation. Most used coils (97.0% [475/490]) and biological glue (72.0% [353/490]) as embolic materials, and 78.5% (428/545) routinely performed intraoperative portal pressure gradient measurements. When selecting TIPS stents, 57.1% (311/545) chose viator‐specific stents, and 57.2% (312/545) chose conventional anticoagulation after TIPS. Conventional anticoagulation after TIPS is over a time interval of 3–6 months (55.4% [173/312]). The limitation of TIPS surgery is mainly its cost (72.3% [394/545]) and insufficient understanding of the procedure by doctors in other related departments (77.4% [422/545]). Most of the hospital teams accept the use of domestic instruments in TIPS surgery (92.7% [505/545]). This survey shows that TIPS is an essential part of the treatment of portal hypertension in China. TIPS is widely used in Chinese patients with portal hypertension, and this survey presents a more comprehensive picture of the options and difficulties encountered in the implementation of TIPS. In the future, it is necessary to promote TIPS technology and further standardize surgical indications, routine operations, and instrument application. A survey analysis of TIPS for portal hypertension in China. TIPS: Transjugular intrahepatic portosystemic shunt. The findings of this paper are the first systematic and comprehensive description of the status of TIPS intervention in China, and a comprehensive understanding of the current number of TIPS cases, indications, surgical details, and difficulties faced in China.This paper includes a larger number of cases, a detailed questionnaire design, and realistic results, which lays a good foundation for future large‐scale cooperation in the field of TIPS in China. The findings of this paper are the first systematic and comprehensive description of the status of TIPS intervention in China, and a comprehensive understanding of the current number of TIPS cases, indications, surgical details, and difficulties faced in China. This paper includes a larger number of cases, a detailed questionnaire design, and realistic results, which lays a good foundation for future large‐scale cooperation in the field of TIPS in China.

The mechanical performance and surface friction of graphene oxide (GO) were found to inversely depend on the number of layers. Here, we demonstrate the non-monotonic layer-dependence of the nanowear resistance of GO nanosheets deposited on a native silicon oxide substrate. As the thickness of GO increases from ∼0.9 nm to ∼14.5 nm, the nanowear resistance initially demonstrated a decreasing and then an increasing tendency with a critical number of layers of 4 (∼3.6 nm in thickness). This experimental tendency corresponds to a change of the underlying wear mode from the overall removal to progressive layer-by-layer removal. The phenomenon of overall removal disappeared as GO was deposited on an H-DLC substrate with a low surface energy, while the nanowear resistance of thicker GO layers was always higher. Combined with density functional theory calculations, the wear resistance of few-layer GO was found to correlate with the substrate’s surface energy. This can be traced back to substrate-dependent adhesive strengths of GO, which correlated with the GO thickness originating from differences in the interfacial charge transfer. Our study proposes a strategy to improve the antiwear properties of 2D layered materials by tuning their own thickness and/or the interfacial interaction with the underlying substrate.

The definition of atomic-scale contact is a very ambiguous issue owing to the discrete atomic arrangement, which hinders the development of contact theory and nano-tribological techniques. In this work, we studied the atomic-scale contact area and their correlations with friction force based on three distinct contact definitions (interatomic distance, force, and interfacial chemical bonds) by performing large-scale atomistic simulations on a typical ball-on-disk contact model. In the simulations, the measured contact areas defined by interatomic distance, force, and interfacial chemical bonds (referred as to Adist, Aforce, and Abond, respectively) are not equivalent at all, while we interestingly clarify that only Adistis consistent with the one calculated by continuum Hertz contact mechanics, and moreover, only Abondis proportional to the friction force indicating that Abondis the dominant one for determining materials’ frictional behaviors. The above fundamental insights into the atomic-scale contact problems are useful to deeply understand the origins of tribological phenomena and contribute to the further prediction of atomic-scale friction.

Introduction:Lenvatinib is the first-line treatment for advanced hepatocellular carcinoma (HCC). We aimed to compare the clinical outcomes of lenvatinib plus drug-eluting beads transarterial chemoembolization (DEB-TACE) versus lenvatinib alone in real-world practice. Methods:This retrospective analysis included 142 consecutive patients who received lenvatinib plus DEB-TACE and 69 patients who received lenvatinib alone as first-line treatment from 15 Chinese academic centers from November 2018 to November 2019. Overall survival (OS), progression-free survival (PFS), objective response rate (ORR) were evaluated by modified Response Evaluation Criteria in Solid Tumors criteria, and safety profiles were compared between the two groups. Results:The median OS and PFS were significantly longer in the combined therapy group than in the monotherapy group in whole cohort (median OS, 15.9 vs. 8.6 months, p= 0.0022; median PFS, 8.6 vs. 4.4 months, p< 0.001) and after propensity score matching analysis (median OS, 13.8 vs. 7.8 months, p= 0.03; median PFS, 7.8 vs. 4.5 months, p= 0.009). Moreover, the treatment option was an independent prognostic factor for OS and PFS with adjustment based upon baseline characteristics (adjusted hazard ratio [HR]: 0.53, 95% confidence interval [CI]: 0.36–0.78, p= 0.001, and adjusted HR: 0.42, 95% CI: 0.30–0.60, p< 0.001, respectively) and propensity score (adjusted HR: 0.52, 95% CI: 0.36–0.76, p= 0.001, and adjusted HR: 0.46, 95% CI: 0.33–0.64, p< 0.001, respectively). Moreover, a greater ORR was observed in the combined group (ORR: 46.48% vs. 13.05%, p< 0.001). Furthermore, the most common adverse events (AEs) were elevated aspartate aminotransferase (54.9%) and fatigue (46.4%) in the lenvatinib plus DEB-TACE group and lenvatinib group, respectively. Most AEs were mild-to-moderate and manageable. Conclusions:With well-tolerated safety, lenvatinib plus DEB-TACE was more effective than lenvatinib monotherapy in improving OS, PFS, and ORR. Thus, it may be a promising treatment for advanced HCC. Future prospective studies confirming these findings are warranted.

Confocal microscopy1remains a major workhorse in biomedical optical microscopy owing to its reliability and flexibility in imaging various samples, but suffers from substantial point spread function anisotropy, diffraction-limited resolution, depth-dependent degradation in scattering samples and volumetric bleaching2. Here we address these problems, enhancing confocal microscopy performance from the sub-micrometre to millimetre spatial scale and the millisecond to hour temporal scale, improving both lateral and axial resolution more than twofold while simultaneously reducing phototoxicity. We achieve these gains using an integrated, four-pronged approach: (1) developing compact line scanners that enable sensitive, rapid, diffraction-limited imaging over large areas; (2) combining line-scanning with multiview imaging, developing reconstruction algorithms that improve resolution isotropy and recover signal otherwise lost to scattering; (3) adapting techniques from structured illumination microscopy, achieving super-resolution imaging in densely labelled, thick samples; (4) synergizing deep learning with these advances, further improving imaging speed, resolution and duration. We demonstrate these capabilities on more than 20 distinct fixed and live samples, including protein distributions in single cells; nuclei and developing neurons in Caenorhabditis elegansembryos, larvae and adults; myoblasts in imaginal disks of Drosophilawings; and mouse renal, oesophageal, cardiac and brain tissues.

Diamond-like carbon (DLC) film has been developed as an extremely effective lubricant to reduce energy dissipation; however, most films should undergo running-in to achieve a super-low friction state. In this study, the running-in behaviors of an H-DLC/Al2O3pair were investigated through a controllable single-asperity contact study using an atomic force microscope. This study presents direct evidence that illustrates the role of transfer layer formation and oxide layer removal in the friction reduction during running-in. After 200 sliding cycles, a thin transfer layer was formed on the Al2O3tip. Compared with a clean tip, this modified tip showed a significantly lower adhesion force and friction force on the original H-DLC film, which confirmed the contribution of the transfer layer formation in the friction reduction during running-in. It was also found that the friction coefficient of the H-DLC/Al2O3pair decreased linearly as the oxygen concentration of the H-DLC substrate surface decreased. This phenomenon can be explained by a change in the contact surface from an oxygen termination with strong hydrogen bond interactions to a hydrogen termination with weak van der Waals interactions. These results provide new insights that quantitatively reveal the running-in mechanism at the nanoscale, which may help with the design optimization of DLC films for different environmental applications.

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Transjugular intrahepatic portosystemic shunt (TIPS) is a life-saving procedure for patients with severe portal hypertension and persistent variceal bleeding. Stent fracture is a rare and severe complication; however, its cause and mechanisms remain poorly defined. This case helps understand the factors contributing to its occurrence, complications, and subsequent poor outcomes. A 63-year-old male was presented with ruptured bare stent after a TIPS procedure. The upper edge of the bare stent was ruptured, and its fraction subsequently migrated to the entrance of the right atrium. Meanwhile, a mural thrombus was formed in the inferior vena cava. A surgery for the removal of free fracture was planned for preventing the form of pulmonary embolism. Before the surgery, the fracture was shifted to the right inferior pulmonary artery. Therefore, the surgery was canceled for further evaluation. Then, hematemesis suddenly occurred with a high possibility of variceal bleeding and/or gastric ulcer bleeding. Despite comprehensive treatments, the patient symptoms were still worsened with the development of chest tightness, shortness of breath, severe hypoxia, and heart failure. Finally, the patient succumbed to systemic multiorgan failure and death. Taken together, a ruptured unstable stent should be removed as early as the patient is hemodynamically stable, as it is difficult to balance between hemostasis therapy and anticoagulation treatment in patients with liver-cirrhosis-related severe portal hypertension. Physicians should be on high alert of the potential complications of bare stent rapture after TIPS.

Mechanochemical strategies are widely used in various fields, ranging from friction and wear to mechanosynthesis, yet how the mechanical stress activates the chemical reactions at the electronic level is still open. We used first-principles density functional theory to study the rule of the stress-modified electronic states in transmitting mechanical energy to trigger chemical responses for different mechanochemical systems. The electron density redistribution among initial, transition, and final configurations is defined to correlate the energy evolution during reactions. We found that stress-induced changes in electron density redistribution are linearly related to activation energy and reaction energy, indicating the transition from mechanical work to chemical reactivity. The correlation coefficient is defined as the term “interface reactivity coefficient” to evaluate the susceptibility of chemical reactivity to mechanical action for material interfaces. The study may shed light on the electronic mechanism of the mechanochemical reactions behind the fundamental model as well as the mechanochemical phenomena.

The low wear resistance of macroscale graphene coatings does not match the ultrahigh mechanical strength and chemical inertness of the graphene layer itself; however, the wear mechanism responsible for this issue at low mechanical stress is still unclear. Here, we demonstrate that the susceptibility of the graphene monolayer to wear at its atomic step edges is governed by the mechanochemistry of frictional interfaces. The mechanochemical reactions activated by chemically active SiO2microspheres result in atomic attrition rather than mechanical damage such as surface fracture and folding by chemically inert diamond tools. Correspondingly, the threshold contact stress for graphene edge wear decreases more than 30 times to the MPa level, and mechanochemical wear can be described well with the mechanically assisted Arrhenius-type kinetic model, i.e., exponential dependence of the removal rate on the contact stress. These findings provide a strategy for improving the antiwear of graphene-based materials by reducing the mechanochemical interactions at tribological interfaces.

To evaluate the clinical efficacy of infusion of gemcitabine (GEM) and fluorouracil (5-FU)through the celiac artery and superior mesenteric artery in the treatment of pancreatic carcinoma (PC).

Introduction:The benefits of combining transarterial chemoembolization (TACE) and sorafenib (TACE-S) over TACE alone for treatment of unresectable hepatocellular carcinoma (HCC) remain controversial. Yet, such populations are heterogeneous in terms of baseline characteristics. Objective:To investigate the predictors of survival benefits from added sorafenib and identify the potential candidates for TACE-S. Methods:This multicenter observational study was conducted in 17 Chinese tertiary hospitals for patients with unresectable, liver-confined HCC. Eligible patients with performance status score of ≤1 and Child-Pugh score of ≤7 were treated with TACE or TACE-S. Interactions between treatment and baseline variables were evaluated to find indicators for survival benefits, based on which the patients were stratified. Multivariate models adjusted for baseline characteristics or propensity score were used to compare overall survival (OS) and time to tumor progression (TTP). Results:From January 2009 to December 2015, 1,719 consecutive patients received TACE (n= 1,406) or TACE-S (n= 313). Although TACE-S compared with TACE improved TTP (adjusted hazard ratio [HR] 0.75, p= 0.008), no difference in OS was observed (adjusted HR 0.87, p= 0.090). Nevertheless, the tumor burden (sum of maximum diameter of largest tumor [cm] and tumor number) and albumin-bilirubin (ALBI) score independently predicted the survival benefits from added sorafenib (interaction p< 0.001). For patients with either moderate tumor burden (7–13) or low ALBI score (no more than –2.8) defined as candidates, TACE-S prolonged OS (adjusted HR 0.73, p= 0.003) and TTP (adjusted HR 0.72, p= 0.014) compared to TACE alone, whereas its superiority disappeared in non-candidates. Conclusions:Not all unresectable HCC patients but those with moderate tumor burden or low ALBI score achieve survival benefits from TACE-S compared with TACE alone. Future randomized controlled trials focusing on the subset are warranted.

This study aimed to investigate the efficacy, safety, and prognostic factors of drug-eluting beads transarterial chemoembolization (DEB-TACE) in treating Chinese patients with liver cancer. A total of 367 liver cancer patients from 24 medical centers were consecutively enrolled in this multiple-center, prospective cohort study, including 275 hepatocellular carcinoma (HCC) cases, 37 intrahepatic cholangiocarcinoma (ICC) cases, and 55 secondary liver cancer cases. All the patients received CalliSpheres®DEB-TACE treatment. Treatment response, overall survival (OS), change of liver function, and adverse events (AEs) were assessed. DEB-TACE treatment achieved 19.9% complete response (CR) and 79.6% objective response rate (ORR), with mean OS of 384 days [95% confidence interval (CI): 375‐393 days]. CR and ORR were both higher in HCC patients compared with primary ICC patients and secondary liver cancer patients, while no difference was discovered in OS. Portal vein invasion was an independent risk factor for CR, while portal vein invasion, previous conventional TACE (cTACE) treatment, and abnormal blood creatinine (BCr) were independent risk factors for ORR. In addition, largest nodule size ≥5.0 cm, abnormal albumin (ALB), and abnormal total bilirubin (TBIL) independently correlated with unfavorable OS. Most liver function indexes were recovered to baseline levels at 1‐3 months after DEB-TACE. Common AEs were pain, fever, vomiting, and nausea; most of them were at mild grade. CalliSpheres®DEB-TACE is efficient and well tolerated in Chinese liver cancer patients. Portal vein invasion, previous cTACE treatment, largest nodule size, abnormal BCr, ALB, and TBIL correlate with worse prognosis independently.

Statement of RetractionWe, the Editors and Publisher of the journal Cell Cycle, have retracted the following article:Jing Ai, Junhui Sun, Guanhui Zhou, Tongyin Zhu, and Li Jing. Long non-coding RNA GAS6-AS1 acts as a ceRNA for microRNA-585, thereby increasing EIF5A2 expression and facilitating hepatocellular carcinoma oncogenicity. Cell Cycle. 2020;19(7):742-757. doi: 10.1080/15384101.2020.1729323.Since publication, concerns have been raised about the integrity of the data in the article. When approached for an explanation, the authors have been unable to address all the concerns raised and have not been able to provide their original data in the required format. As verifying the validity of published work is core to the integrity of the scholarly record, we are therefore retracting the article. The corresponding author listed in this publication has been informed. The authors do not agree with the retraction.We have been informed in our decision-making by our policy on publishing ethics and integrity and the COPE guidelines on retractions.The retracted article will remain online to maintain the scholarly record, but it will be digitally watermarked on each page as ‘Retracted’.

The purpose of this study was to investigate the efficacy and safety of drug-eluting beads transarterial chemoembolization (DEB-TACE) treatment in Chinese hepatocellular carcinoma (HCC) patients and the prognostic factors for treatment response as well as survival. A total of 275 HCC patients were included in this prospective study. Treatment response was assessed by modified Response Evaluation Criteria in Solid Tumors (mRECIST), and progression-free survival (PFS) as well as overall survival (OS) were determined. Liver function and adverse events (AEs) were assessed before and after DEB-TACE operation. Complete response (CR), partial response (PR), and objective response rate (ORR) were 22.9%, 60.7%, and 83.6%, respectively. The mean PFS was 362 (95% CI: 34.9‐375) days, the 6-month PFS rate was 89.4 ± 2.1%, while the mean OS was 380 (95% CI: 370‐389) days, and the 6-month OS rate was 94.4 ± 1.7%. Multivariate logistic regression revealed that portal vein invasion (p = 0.011) was an independent predictor of worse clinical response. Portal vein invasion (p = 0.040), previous cTACE treatment (p = 0.030), as well as abnormal serum creatinine level (BCr) (p = 0.017) were independent factors that predicted worse ORR. In terms of survival, higher Barcelona Clinic Liver Cancer (BCLC) stage (p = 0.029) predicted for worse PFS, and abnormal albumin (ALB) (p = 0.011) and total serum bilirubin (TBIL) (p = 0.009) predicted for worse OS. The number of patients with abnormal albumin, total protein (TP), TBIL, alanine aminotransferase (ALT), and aspartate aminotransferase (AST) were augmented at 1 week posttreatment and were similar at 1‐3 months compared with baseline. The most common AEs were pain, fever, nausea, and vomiting, and no severe AEs were observed in this study. DEB-TACE was effective and tolerable in treating Chinese HCC patients, and portal vein invasion, previous cTACE treatment, abnormal BCr, ALB, and TBIL appear to be important factors that predict worse clinical outcome.

ObjectivesEarly placement of transjugular intrahepatic portosystemic shunt (TIPS) has been shown to improve survival in high-risk patients (Child-Pugh B plus active bleeding at endoscopy or Child-Pugh C 10–13) with cirrhosis and acute variceal bleeding (AVB). However, early TIPS criteria may overestimate the mortality risk in a significant proportion of patients, and the survival benefit conferred by early TIPS in such patients has been questioned. Alternative criteria have been proposed to refine the criteria used to identify candidates for early TIPS. Nevertheless, the true survival benefit provided (or not) by early TIPS compared with standard treatment in the different risk categories has not been investigated in specifically designed comparative studies.DesignWe collected data on 1425 consecutive patients with cirrhosis and AVB who were admitted to 12 university hospitals in China between December 2010 and June 2016. Of these, 206 patients received early TIPS, and 1219 patients received standard treatment. The Fine and Gray competing risk regression model was used to compare the outcomes between the two groups that were stratified based on the currently available risk stratification systems after adjusting for liver disease severity and other potential confounders.ResultsOverall, early TIPS was associated with an 80% relative risk reduction (RRR) in mortality at 6 weeks (adjusted HR=0.20; 95% CI: 0.10 to 044; p<0.001) and 51% RRR at 1 year (adjusted HR=0.49, 95% CI: 0.32 to 0.73; p<0.001) compared with standard treatment. In stratification analyses, the RRRs in mortality did not significantly differ among the risk categories. However, the absolute risk reductions (ARRs) of mortality were more pronounced in high-risk patients. The ARRs at 6 weeks were −2.1%, −10.2% and −32.4% in Model for End-stage Liver Disease (MELD) ≤11, 12–18 and ≥19 patients and were −1.5%, −9.1% and −23.2% in Child-Pugh A, B and C patients, respectively (interaction tests, p<0.001 for both criteria). The ARRs for mortality at 1 year were −1.7%, −5.4% and −32.7% in MELD ≤11, 12–18 and ≥19 patients, respectively, and −3.6%, −5.2% and −20.3% in Child-Pugh A, B and C patients, respectively (interaction tests, p<0.001 for both criteria). After adjusting for liver disease severity and other potential confounders, a survival benefit was observed in MELD ≥19 or Child-Pugh C patients but not in MELD ≤11 or Child-Pugh A patients. In MELD 12–18 patients, a survival benefit was observed within 6 weeks but not at 1 year. In Child-Pugh B patients, a survival benefit was observed in those with active bleeding but not those without active bleeding. However, the evaluation of active bleeding was associated with a high interobserver variability. Furthermore, early TIPS was associated with a significantly reduced incidence of failure to control bleeding or rebleeding and new or worsening ascites, without increasing the risk of overt hepatic encephalopathy.ConclusionsEarly TIPS was associated with improved survival in patients with MELD ≥19 or Child-Pugh C cirrhosis but not in patients with MELD ≤11 or Child-Pugh A cirrhosis. For MELD 12–18 or Child-Pugh B patients, future studies addressing optimal selection criteria for early TIPS remain highly warranted.

Mitochondrial Ca2+overload is proposed to regulate cell death via opening of the mitochondrial permeability transition pore. It is hypothesized that inhibition of the mitochondrial Ca2+uniporter (MCU) will prevent Ca2+accumulation during ischemia/reperfusion and thereby reduce cell death. To address this, we evaluate mitochondrial Ca2+in ex-vivo-perfused hearts from germline MCU-knockout (KO) and wild-type (WT) mice using transmural spectroscopy. Matrix Ca2+levels are measured with a genetically encoded, red fluorescent Ca2+indicator (R-GECO1) using an adeno-associated viral vector (AAV9) for delivery. Due to the pH sensitivity of R-GECO1 and the known fall in pH during ischemia, hearts are glycogen depleted to decrease the ischemic fall in pH. At 20 min of ischemia, there is significantly less mitochondrial Ca2+in MCU-KO hearts compared with MCU-WT controls. However, an increase in mitochondrial Ca2+is present in MCU-KO hearts, suggesting that mitochondrial Ca2+overload during ischemia is not solely dependent on MCU.

Mitochondrial network connectivity enables rapid communication and distribution of potential energy throughout the cell. However, this connectivity puts the energy conversion system at risk, because damaged elements could jeopardize the entire network. Here, we demonstrate the mechanisms for mitochondrial network protection in heart and skeletal muscle (SKM). We find that the cardiac mitochondrial reticulum is segmented into subnetworks comprising many mitochondria linked through abundant contact sites at highly specific intermitochondrial junctions (IMJs). In both cardiac and SKM subnetworks, a rapid electrical and physical separation of malfunctioning mitochondria occurs, consistent with detachment of IMJs and retraction of elongated mitochondria into condensed structures. Regional mitochondrial subnetworks limit the cellular impact of local dysfunction while the dynamic disconnection of damaged mitochondria allows the remaining mitochondria to resume normal function within seconds. Thus, mitochondrial network security is comprised of both proactive and reactive mechanisms in striated muscle cells.

It is well-known that the electron nature of a solid in contact plays a predominant role in determining the many properties of the contact systems, but the general rules of electron coupling that govern interfacial friction remain an open issue for the surface/interface community. Here, density functional theory calculations were used to investigate the physical origins of friction of solid interfaces. It was found that interfacial friction can be inherently traced back to the electronic barrier to the change in the contact configuration of the joints in slip due to the resistance of energy level rearrangement leading to electron transfer, which applies for various interface types ranging from van der Waals, metallic, and ionic to covalent joints. The variation of the electron density accompanying contact conformation changes along the sliding pathways is defined to track the frictional energy dissipation process occurring in slip. The results demonstrate that the frictional energy landscapes evolve synchronously with responding charge density evolution along sliding pathways, yielding an explicitly linear dependence of frictional dissipation on electronic evolution. The correlation coefficient enables us to interpret the fundamental concept of shear strength. The present charge evolution model thereby provides insights into the classic hypothesis that the friction force scales with the real contact area. This may shed light on the intrinsic origin of friction at the electronic level, opening the way to the rational design of nanomechanical devices as well as the understanding of the natural faults.

Wear of sliding contacts causes device failure and energy costs; however, the microscopic principle in activating wear of the interfaces under stress is still open. Here, the typical nanoscale wear, in the case of silicon against silicon dioxide, is investigated by single-asperity wear experiments and density functional theory calculations. The tests demonstrate that the wear rate of silicon in ambient air increases exponentially with stress and does not obey classical Archard’s law. Series calculations of atomistic wear reactions generally reveal that the mechanical stress linearly drives the electron transfer to activate the sequential formation and rupture of interfacial bonds in the atomistic wear process. The atomistic wear model is thus resolved by combining the present stress-driven electron transfer model with Maxwell–Boltzmann statistics. This work may advance electronic insights into the law of nanoscale wear for understanding and controlling wear and manufacturing of material surfaces.

Atomically thin two-dimensional (2D) materials are excellent candidates for utilization as a solid lubricant or additive at all length scales from macro-scale mechanical devices to micro/nano-electromechanical systems (MEMS/NEMS). In such applications, wear resistance of ultrathin 2D materials is critical for sustained lubrication performance. Here, we investigated the wear of fluorinated graphene (FG) nanosheets deposited on silicon surfaces using atomic force microscopy (AFM) and discovered that the wear resistance of FG improves as the FG thickness decreases from 4.2 to 0.8 nm (corresponding to seven layers to single layer) and the surface energy of the substrate underneath the FG nanosheets increases. On the basis of density function theory (DFT) calculations, the negative correlation of wear resistance to FG thickness and the positive correlation to substrate surface energy could be explained with the degree of interfacial charge transfer between FG and substrate which affects the strength of FG adhesion to the substrate.

Optical methods for measuring intracellular ions including Ca2+revolutionized our understanding of signal transduction. However, these methods are not extensively applied to intact organs due to issues including inner filter effects, motion, and available probes. Mitochondrial Ca2+is postulated to regulate cell energetics and death pathways that are best studied in an intact organ. Here, we develop a method to optically measure mitochondrial Ca2+and demonstrate its validity for mitochondrial Ca2+and metabolism using hearts from wild-type mice and mice with germline knockout of the mitochondria calcium uniporter (MCU-KO). We previously reported that germline MCU-KO hearts do not show an impaired response to adrenergic stimulation. We find that these MCU-KO hearts do not take up Ca2+, consistent with no alternative Ca2+uptake mechanisms in the absence of MCU. This approach can address the role of mitochondrial Ca2+to the myriad of functions attributed to alterations in mitochondrial Ca2+.

Nitric oxide (NO) plays an important role in the regulation of cardiovascular function. S-nitrosylation, the covalent attachment of an NO moiety to sulfhydryl residues of proteins, resulting in the formation of S-nitrosothiols (SNOs), is a prevalent posttranslational protein modification involved in redox-based cellular signaling. Under physiologic conditions, protein S-nitrosylation and SNOs provide protection preventing further cellular oxidative and nitrosative stress. However, oxidative stress and the resultant dysfunction of NO signaling have been implicated in the pathogenesis of cardiovascular diseases.

The skeletal muscle Ca2+release channel/ryanodine receptor (RyR1) is a prototypic redox-responsive ion channel. Nearly half of the 101 cysteines per RyR1 subunit are kept in a reduced (free thiol) state under conditions comparable with resting muscle. Here we assessed the effects of physiological determinants of cellular redox state (oxygen tension, reduced (GSH) or oxidized (GSSG) glutathione, and NO/O⨪2(released by 3-morpholinosydnonimine)) on RyR1 redox state and activity. Oxidation of ∼10 RyR1 thiols (from ∼48 to ∼38 thiols/RyR1 subunit) had little effect on channel activity. Channel activity increased reversibly as the number of thiols was further reduced to ∼23/subunit, whereas more extensive oxidation (to ∼13 thiols/subunit) inactivated the channel irreversibly. NeitherS-nitrosylation nor tyrosine nitration contributed to these effects. The results identify at least three functional classes of RyR1 thiols and suggest that 1) the channel may be protected from oxidation by a large reservoir of functionally inert thiols, 2) the channel may be designed to respond to moderate oxidative stress by a change in activation setpoint, and 3) the channel is susceptible to oxidative injury under more extensive conditions.

The reaction of cis-MoO2(S2CNEt2)2 with compounds of Group V elements was studied and the relative reactivities of compounds of Group V elements to abstract oxygen from cis-MoO2(S2CNEt2)2 were found to be in the order: Ph3P>>Et3N∼Ph3As>Ph3Sb>Ph3Bi>Ph3N.

Herein, nonflammable ionic liquid (IL) electrolytes are prepared for dual‐ion batteries (DIBs) by mixing 1‐methyl‐1‐propylpyrrolidinium chloride (P13Cl) or 1‐butyl‐1‐methylpiperidinium chloride (PP14Cl) with 1,2‐dimethyl‐3‐propylimidazolium chloride (DMPICl)/aluminum chloride (AlCl3) to form mixed IL electrolytes. Then, viscosity, ionic conductivity, thermal stability, and electrochemical limits measurements are recorded to reveal the fundamental properties of the mixed IL electrolytes for DIBs, which are not reported previously. As compared with DMPICl/AlCl3(=1 in mole ratio) electrolyte, using electrolyte with addition of P13Cl or PP14Cl (e.g., 0.63 mole to replace DMPICl), the DIB with graphite electrodes show better electrochemical stability. With the addition of 0.63 P13Cl, the Coulombic efficiency of the DIB reaches up to 96.7% (≈91% for DMPICl/AlCl3); however, specific capacity loss should be considered. In general, ideas for designing higher energy density electrochemical energy storage devices are provided. Mixed ionic liquid (IL) electrolytes are prepared for dual‐ion batteries (DIBs) by mixing 1‐methyl‐1‐propylpyrrolidinium chloride or 1‐butyl‐1‐methylpiperidinium chloride with 1,2‐dimethyl‐3‐propylimidazolium chloride/aluminum chloride. Physical and electrochemical properties of mixed IL electrolytes are revealed herein. Coulombic efficiency of a DIB with pyrrolidinium‐based mixed IL electrolyte can be up to 96.7%.

Symmetric, aromatic disulfides (I) containing electron‐donating and electron‐withdrawing groups are oxidized equally well by trichloroisocyanuric acid upon grinding with a pestle in a mortar.