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Tracking the dynamic distribution of native proteins in living cells or tissues in real time is essential for understanding the functional mechanisms involved in their physiological or pathological processes. The β3-adrenergic receptor (β3-AR) has important biological functions. It is expected to be a diagnostic indicator for aging, yet current probes for β-ARs are unable to dynamically monitor β3-AR in real time, which impedes the progress of β3-AR research. Here, we developed a ligand-directed anchoring probe, β3-ARP, that precisely covalently anchors with native β3-AR in living cells, for the diagnosis of senescence. The ligand-directed anchoring probe selectively recognizes and traces β3-AR and can achieve dynamic observation and monitoring of β3-AR in living cells, including the interaction between lipid droplets and mitochondria. Moreover, we were able to directly probe the distribution of β3-AR in various organs of aging mice in situ and track the location of native β3-AR in different types of primary neuronal cells using β3-ARPand two-photon imaging, which revealed the aberrant accumulation of lipid droplets and the distribution of β3-AR in neurological diseases. This research has resulted in a new covalently anchoring fluorescent probe, β3-ARP, which could serve as a powerful tool to explore the link between β3-AR and age-related diseases.

Background: The impact of metabolic dysfunction-associated fatty liver disease (MAFLD) on laparoscopic liver resection (LLR) for hepatocellular carcinoma (HCC) remains unclear. This study aimed to compare the outcomes of LLR for MAFLD-HCC and Non-MAFLD-HCC. Methods: Patients with HCC who received LLR between October 2017 and July 2021 were enrolled. Inverse probability of treatment weighting (IPTW) was used to generate adjusted comparisons. Both short- and long-term outcomes were evaluated accordingly. Results: A total of 887 patients were enrolled, with 140 in MAFLD group and 747 in Non-MAFLD group. After IPTW adjustment, baseline factors were well matched. The MAFLD group was associated with more blood loss (210 vs 150 ml, p= 0.022), but with similar postoperative hospital stays and complication rates. The 1- and 3-year overall survival rates were 97.4% and 92.5% in MAFLD group, and 97.5% and 88.3% in Non-MAFLD group, respectively (p= 0.14). The 1- and 3-year disease-free survival rates were 84.8% and 62.9% in MAFLD group, and 80.2% and 58.8% in Non-MAFLD group, respectively (p= 0.31). Conclusions: LLR for MAFLD-HCC was associated with more blood loss but with comparable postoperative recovery and long-term survival compared with Non-MAFLD-HCC patients. LLR is feasible and safe for HCC patients with MAFLD background. Graphical abstract:

Hydrogen sulfide (H2S), a critical gas signaling molecule, and N-acetyltransferase 2 (NAT2), a key enzyme in drug metabolism, are both known active biomarkers for liver function. However, the interactions and effects of H2S and NAT2 in living cells or lesion sites remain unknown due to the lack of imaging tools to achieve simultaneous detection of these two substances, making it challenging to implement real-time imaging and precise tracking. Herein, we report an activity-based two-photon fluorescent probe, TPSP-1, for the cascade detection of H2S and NAT2 in living liver cells. Continuous conversion from TPSP-1to TPSP-3was achieved in liver cells and tissues. Significantly, leveraging the outstanding optical properties of this two-photon fluorescent probe, TPSP-1, has been effectively used to identify pathological tissue samples directly from clinical liver cancer patients. This work provides us with this novel sensing and two-photon imaging probe, which can be used as a powerful tool to study the physiological functions of H2S and NAT2 and will help facilitate rapid and accurate diagnosis and therapeutic evaluation of hepatocellular carcinoma.

The Kv4.3 channel features fast N-type inactivation and also undergoes a slow C-type inactivation. The gain-of-function mutations of Kv4.3 channels cause an inherited disease called Brugada syndrome (BrS), characterized by a shortened duration of cardiac action potential repolarization and ventricular arrhythmia. The sulfonylurea drug gliquidone, an ATP-dependent K+channel antagonist, is widely used for the treatment of type 2 diabetes. Here, we report a novel role of gliquidone in inhibiting Kv4.3 and Kv4.3/KChIP2 channels that encode the cardiac transient outward K+currents responsible for the initial phase of action potential repolarization. Gliquidone results in concentration-dependent inhibition of both Kv4.3 and Kv4.3/KChIP2 fast or steady-state inactivation currents with an IC50of approximately 8 μM. Gliquidone also accelerates Kv4.3 channel inactivation and shifts the steady-state activation to a more depolarizing direction. Site-directed mutagenesis and molecular docking reveal that the residues S301 in the S4 and Y312A and L321A in the S4-S5 linker are critical for gliquidone-mediated inhibition of Kv4.3 currents, as mutating those residues to alanine significantly reduces the potency for gliquidone-mediated inhibition. Furthermore, gliquidone also inhibits a gain-of-function Kv4.3 V392I mutant identified in BrS patients in voltage- and concentration-dependent manner. Taken together, our findings demonstrate that gliquidone inhibits Kv4.3 channels by acting on the residues in the S4 and the S4-S5 linker. Therefore, gliquidone may hold repurposing potential for the therapy of Brugada syndrome.SIGNIFICANCE STATEMENTWe describe a novel role of gliquidone in inhibiting cardiac Kv4.3 currents and the channel gain-of-function mutation identified from patients with Brugada syndrome, suggesting its repurposing potential for therapy for the heart disease.

In the era of big data, information is growing at an explosive rate and shows a variety of characteristics. Accordingly, how to scientifically and efficiently manage and analyze massive amounts of data has become an urgent problem for technical enterprises and government departments. Among all proposed modern techniques to handle data on large scales, text analytics directly on compression (TADOC) stands out with an innovative idea of operating on the compression and has substantial potential in various applications. Meanwhile, DCU (Deep Computing Unit), a new Chinese domestic accelerator with high acceleration performance, exhibits tremendous adaptability in transplanting the work of TADOC. Therefore, this paper proposes D-TADOC, a compressed data direct computing technology for Chinese dataset on DCU, which can effectively process data in Chinese without decompression and visualize the analytics results. There are three key components in D-TADOC. First, we incorporate TADOC with the word segmentation tool in the data preprocessing module, enabling TADOC to analyze not only English, but also Chinese texts. Second, we design the parallel processing module on the DCU architecture. Third, we develop the result visualization module, which supports the user-friendly presentation of the text analytics outcomes. We conduct experiments of D-TADOC on Sugon’s cloud computing service platform with diverse public datasets and evaluate the performance. The experiment results show that D-TADOC achieves an average speedup of 40.5 ×compared with the TADOC baseline on the CPU, demonstrating the adaptability of DCU for TADOC tasks as well as the efficiency of D-TADOC on compressed text analytics.

An intestinal stoma is a surgically formed exteriorisation of the large or small bowel on to the anterior abdomen wall, to enable faeces to be excreted from the body. Patients living with a stoma may encounter physical, psychological, and social barriers and challenges. Stoma self-management education is essential to improving self-care competence, and patients who perceive the benefits of self-management education show a better adjustment to living with a stoma. This literature review explored the effectiveness of patient education interventions in improving the self-care knowledge and skills of patients living with an ostomy. The findings from the nine studies reviewed showed that self-management education approaches are effective in improving patients’ self-care. The application of different approaches to ostomy self-management education, such as a transtheoretical model, chronic care model, telehealth and multimediabased programmes – helped improve patients’ self-care ability. The review also found that patients needed at least 3 months to develop the skills and maintain their ability to self-care. In addition, two education sessions provided to patients in hospital pre-discharge appeared sufficient for improving and maintaining self-care abilities. Where patients received education in hospital post-surgery, 2 or 3 sessions over 7 days were found to be sufficient to provide them with stoma care skills. Education sessions based on the transtheoretical model and chronic care model or telehealth helped maintain and reinforce self-care behaviours following discharge.

The adsorptive removal of methylene blue (MB) from aqueous solution is often executed by attapulgite (ATP) due to its unique one-dimensional nanoscale structure and low-cost, abundant, eco-friendly advantages. Another commonly used material for this job is activated carbon. In this study, a novel composite porous ceramsite was prepared by combining activated carbon and ATP clay to remove MB from an aqueous solution. The composite porous ceramsite, calcined at 450 °C (CPC-450), was characterized by SEM, FT-IR, XRD, and BET specific surface area measurements. It possessed a high specific surface area of 313.606 m2/g and exhibited superior adsorption capacity toward MB than that of raw ATP. Consequently, a 99.6% MB removal efficiency was achieved at adsorption equilibrium. Moreover, the maximum adsorption capacity of CPC-450 increased compared to the raw ATP, with a value of 50.68 mg/g, and it could be reused more than 6 times. The adsorption experiment was executed at different conditions, and the Langmuir isotherm model and pseudo-second-order kinetic equation fitted the obtained data very well. The main driving forces for the adsorption process were found to be hydrogen-bonding interaction, electrostatic attraction, and chemical association.

An intestinal stoma is a surgically formed exteriorisation of the large or small bowel on to the anterior abdomen wall, to enable faeces to be excreted from the body. Patients living with a stoma may encounter physical, psychological, and social barriers and challenges. Stoma self-management education is essential to improving self-care competence, and patients who perceive the benefits of self-management education show a better adjustment to living with a stoma. This literature review explored the effectiveness of patient education interventions in improving the self-care knowledge and skills of patients living with an ostomy. The findings from the nine studies reviewed showed that self-management education approaches are effective in improving patients' self-care. The application of different approaches to ostomy self-management education, such as a transtheoretical model, chronic care model, telehealth and multimedia-based programmes – helped improve patients' self-care ability. The review also found that patients needed at least 3 months to develop the skills and maintain their ability to self-care. In addition, two education sessions provided to patients in hospital pre-discharge appeared sufficient for improving and maintaining self-care abilities. Where patients received education in hospital post-surgery, 2 or 3 sessions over 7 days were found to be sufficient to provide them with stoma care skills. Education sessions based on the transtheoretical model and chronic care model or telehealth helped maintain and reinforce self-care behaviours following discharge.

ABSTRACTUp to 40% of transplant recipients treated long-term with tacrolimus (TAC) develop post-transplant diabetes mellitus (PTDM). TAC is an important risk factor for PTDM, but is also essential for immunosuppression after transplantation. Long-term TAC treatment alters the gut microbiome, but the mechanisms of TAC-induced gut microbiota in the pathogenesis of PTDM are poorly characterized. Here, we showed that vancomycin, an inhibitor of bacterial beta-glucuronidase (GUS), prevents TAC-induced glucose disorder and insulin resistance in mice. Metagenomics shows that GUS-producing bacteria are predominant and flourish in the TAC-induced hyperglycemia mouse model, with upregulation of intestinal GUS activity. Targeted metabolomics analysis revealed that in the presence of high GUS activity, the hydrolysis of bile acid (BAs)-glucuronic conjugates is increased and most BAs are overproduced in the serum and liver, which, in turn, activates the ileal farnesoid X receptor (FXR) and suppresses GLP-1 secretion by L-cells. The GUS inhibitor vancomycin significantly eliminated GUS-producing bacteria and inhibited bacterial GUS activity and BAs levels, thereby enhancing L-cell GLP-1 secretion and preventing hyperglycemia. Our results propose a novel clinical strategy for inhibiting the bacterial GUS enzyme to prevent hyperglycemia without requiring withdrawal of TAC treatment. This strategy exerted its effect through the ileal bile acid-FXR-GLP-1 pathway.

The uricosuric drug benzbromarone, widely used for treatment of gout, hyperpolarizes the membrane potential of airway smooth muscle cells, but how it works remains unknown. Here we show a novel role of benzbromarone in activation of large conductance calcium-activated K+channels. Benzbromarone results in dose-dependent activation of macroscopic big potassium (BK) currents about 1.7- to 14.5-fold with an EC50of 111 μM and shifts the voltage-dependent channel activation to a more hyperpolarizing direction about 10 to 54 mV in whole-cell patch clamp recordings. In single-channel recordings, benzbromarone decreases single BKαchannel closed dwell time and increases the channel open probability. Coexpressing β1 subunit also enhances BK activation by benzbromarone with an EC50of 67 μM and a leftward shift of conductance-voltage (G-V) curve about 44 to 138 mV. Site-directed mutagenesis reveals that a motif of three amino acids 329RKK331in the cytoplasmic linker between S6 and C-terminal regulator of potassium conductance (RCK) gating ring mediates the pharmacological activation of BK channels by benzbromarone. Further ex vivo assay shows that benzbromarone causes reduction of tracheal strip contraction. Taken together, our findings demonstrate that uricosuric benzbromarone activates BK channels through molecular mechanism of action involving the channel RKK motif of S6-RCK linker. Pharmacological activation of BK channel by benzbromarone causes reduction of tracheal strip contraction, holding a repurposing potential for asthma and pulmonary arterial hypertension or BK channelopathies.SIGNIFICANCE STATEMENTWe describe a novel role of uricosuric agent benzbromarone in big potassium (BK) channel activation and relaxation of airway smooth muscle contraction. In this study, we find that benzbromarone is an activator of the large-conductance Ca2+- and voltage-activated K+channel (BK channel), which serves numerous cellular functions, including control of smooth muscle contraction. Pharmacological activation of BK channel by the FDA-approved drug benzbromarone may hold repurposing potential for treatment of asthma and pulmonary arterial hypertension or BK channelopathies.

To alleviate kinetics imbalance and capacity insufficiency simultaneously, a novel hierarchical structure (SnCu2Se4/d-Ti3C2Tx/NPC) composed of delaminated Ti3C2Tx, SnCu2Se4nanoparticles, and N-doped porous carbon layers is designed as a battery-type anode for lithium/sodium ion hybrid capacitor (LIC/SIC). The combination of SnCu2Se4nanoparticles with high specific capacity, d-Ti3C2Txwith accelerated ion diffusion path, and NPC with enhanced electronic conductivity makes the SnCu2Se4/d-Ti3C2Tx/NPC composite possess excellent cycling stabilities in half-cell lithium-ion and sodium-ion batteries (LIB and SIB), with capacities of 114 mAh g–1after 6000 cycles at 10 A g–1for LIB and 296 mAh g–1after 900 cycles at 1.0 A g–1for SIB. The rate performance is also outstanding, with recovered capacity of 738 mAh g–1at 0.1 A g–1after cycles at current densities up to 50 A g–1for LIB. Subsequently, LIC and SIC based on the SnCu2Se4/d-Ti3C2Tx/NPC anode and activated carbon cathode exhibit high energy densities of 147.9 and 158.6 Wh kg–1at a power density of 100 W kg–1, respectively. They also possess distinctive long lifespans with capacity retentions of 78 and 81% after 10,000 cycles at 1.0 A g–1, respectively, demonstrating the feasibility of SnCu2Se4/d-Ti3C2Tx/NPC toward energy devices requiring high energy density, power density, and long-term stability.

The emergence of superconductivity in two-dimensional (2D) materials has attracted tremendous research efforts because the origins and mechanisms behind the unexpected and fascinating superconducting phenomena remain unclear. In particular, the superconductivity can survive in 2D systems even with weakened disorder and broken spatial inversion symmetry. Here, structural and superconducting transitions of 2D van der Waals (vdW) hydrogenated germanene (GeH) are observed under compression and decompression processes. GeH possesses a superconducting transition with a critical temperature (Tc) of 5.41 K at 8.39 GPa. A crystalline to amorphous transition occurs at 16.80 GPa, while superconductivity remains. An abnormal increase of Tcup to 6.11 K was observed during the decompression process, while the GeH remained in the 2D amorphous phase. A combination study of in situhigh-pressure synchrotron X-ray diffraction, in situhigh-pressure Raman spectroscopy, transition electron microscopy, and density functional theory simulations suggests that the superconductivity in 2D vdW GeH is attributed to the increased density of states at the Fermi level as well as the enhanced electron–phonon coupling effect under high pressure even in the form of an amorphous phase. The unique pressure-induced phase transition of GeH from 2D crystalline to 2D amorphous metal hydride provides a promising platform to study the mechanisms of amorphous hydride superconductivity.

Genetic loss-of-function mutations of the NaV1.7 channel, abundantly expressed in peripheral nociceptive neurons, cause congenital insensitivity to pain in humans, indicating that selective inhibition of the channel may lead to potential therapy for pain disorders. In this study, we investigated a novel compound, 5-chloro-N-(cyclopropylsulfonyl)-2-fluoro-4-(2-(8-(furan-2-ylmethyl)-8-azaspiro [4.5] decan-2-yl) ethoxy) benzamide (QLS-278) that inhibits NaV1.7 channels and exhibits antinociceptive activity. Compound QLS-278 exhibits inactivation- and concentration-dependent inhibition of macroscopic currents of NaV1.7 channels stably expressed in HEK293 cells with an IC50of 1.2 ± 0.2 μM. QLS-278 causes a hyperpolarization shift of the channel inactivation and delays recovery from inactivation, without any noticeable effect on voltage-dependent activation. In mouse dorsal root ganglion neurons, QLS-278 suppresses native tetrodotoxin-sensitive NaVcurrents and also reduces neuronal firings. Moreover, QLS-278 dose-dependently relieves neuropathic pain induced by spared nerve injury and inflammatory pain induced by formalin without significantly altering spontaneous locomotor activity in mice. Therefore, our identification of the novel compound QLS-278 may hold developmental potential in chronic pain treatment.

Hypertrophic cardiomyopathy (HCM) is an inherited heart disease with left ventricular outflow tract obstruction (LVOTO) in 70% of patients [1].

Searching for quantum spin Hall insulators with large fully opened energy gap to overcome the thermal disturbance at room temperature has attracted tremendous attention because of the robustness of one-dimensional (1D) spin-momentum locked topological edge states in the practical applications of electronic devices and spintronics. Here, we report the investigation of topological nature of monolayer Bi4Br4by the techniques of angle-resolved photoemission spectroscopy (ARPES) and scanning tunneling microscopy. The possible topological nontriviality of 1D edge state integrals within the large energy gap (∼0.2 eV) is revealed by the first-principle calculations. The ARPES measurements at different temperatures show a temperature-induced Lifshitz transition, corresponding to the resistivity anomaly evoked by the chemical potential shift. The connection between the emergency of superconductivity and the Lifshitz transition is discussed.

Quantum spin Hall insulators (QSHIs) have one-dimensional (1D) spin-momentum locked topological edge states (ES) inside the bulk band gap, which can serve as dissipationless channels for the practical applications in low consumption electronics and high performance spintronics. However, obtaining the clean and atomically sharp ES which serves as ideal 1D spin-polarized nondissipative conducting channels is demanding and still a challenge. Here, we report the formation of the quasi-1D Bi4I4nanoribbons on the surface of Bi(111) with the support of the graphene-terminated 6H-SiC(0001) and the direct observation of the topological ES at the step edges by the scanning tunneling microscopy (STM) and spectroscopic-imaging results. The ES reside surround the edge of Bi4I4nanoribbons and exhibits noteworthy robustness against nontime reversal symmetry (non-TRS) perturbations. The theoretical simulations verify the topological nontriviality of 1D ES, which is retained after considering the presence of the underlying Bi(111). Our study supports the existence of topological ES in Bi4I4nanoribbons, benefiting to engineer the topological features by using the 1D nanoribbons as building blocks.

Treatment of chronic pain remains an unmet medical need. The neuronal voltage-gated potassium Kv7/KCNQ/M channel has been implicated as a therapeutic target for chronic pain. However, whether pharmacological activation of the Kv7 channel can alleviate pain remains elusive. In this study, we show that selective activation of native M-currents by a novel channel opener SCR2682 reduces repetitive firings of dorsal root ganglia (DRG) sensory neurons. Intraperitoneal administration of SCR2682 relieves mechanical allodynia and thermal hyperalgesia in rat models of pain induced by complete Freund’s adjuvant (CFA) or spared nerve injury (SNI) in a dose-dependent manner without affecting locomotor activity. The antinociceptive efficacy of SCR2682 can be reversed by the channel-specific blocker XE991. Furthermore, SCR2682 increases Kv7.2/KCNQ2 mRNA and protein expression in DRG neurons from rats in the SNI model of neuropathic pain. Taken together, pharmacological activation of neuronal Kv7 channels by opener SCR2682 can alleviate pain in rats, thus possessing therapeutic potential for chronic pain or hyperexcitability-related neurologic disorders.

ABSTRACTBackgroundEpigallocatechin-3-gallate (EGCG) is the most biologically active catechin of green tea. Tacrolimus (TAC) and cyclosporine A (CsA) are immunosuppressive agents commonly used in clinical organ transplantation. The present study investigated the effect of EGCG on the pharmacokinetics of TAC and CsA in rats and its underlying mechanisms.Research design and methodsEither TAC or CsA was administered to rats intravenously or orally with or without concomitant EGCG. Polymerase Chain Reaction and Western Blot were used to determine the effect of EGCG on drug-metabolizing enzymes (DMEs), drug transporters (DTs) and nuclear receptors (NRs).ResultsThe Cmaxand AUC of TAC were reduced, and V/F and CL/F of TAC were enhanced after co-administration of EGCG. EGCG increased the Cmax, AUC of CsA at 3 ~ 30 mg∙kg-1 dosages, while decreased those parameters at the dosage of 100 mg∙kg-1. EGCG inhibited the mRNA and protein expressions of DMEs and DTs, such as CYP3A1, A2, UGT1A1, Mdr1 and Mrp2, but upregulated the expressions of Car, Pxr and Fxr.ConclusionsThese results revealed consumption of high dose EGCG may cause a significant alteration in pharmacokinetics of TAC and distribution/elimination profiles of CsA through the regulation of DMEs, DTs and NRs.

The volume-regulated anion channel (VRAC) plays a central role in maintaining cell volume in response to osmotic stress. Leucine-rich repeat-containing 8A (LRRC8A) was recently identified as an essential component of VRAC although other Cl−channels were also suggested to contribute to VRAC. VRAC is activated when a cell is challenged with a hypotonic environment or even in isotonic conditions challenged with different stimuli. It is not clear how VRAC is activated and whether activation of VRAC in hypotonic and isotonic conditions share the same mechanism. In this present study, we investigated relative contribution of LRRC8A and anoctamin 1(ANO1) to VRAC currents activated by fetal bovine serum (FBS) in isotonic condition, and studied the role of intracellular Ca2+in this activation. We used CRISPR/Cas9 gene editing approach, electrophysiology, and pharmacology approaches to show that VRAC currents induced by FBS is mostly mediated by LRRC8A in HEK293 cells, but also with significant contribution from ANO1. FBS induces Ca2+transients and these Ca2+signals are required for the activation of VRAC by serum. These findings will help to further understand the mechanism in activation of VRAC.

The narrow visible-light absorption range and a high recombination rate of photo-excited electrons and holes are the main reasons for the confined photocatalytic performance of graphitic carbon nitride (g-C3N4). Here, g-C3N4samples with nitrogen vacancies were synthesized with a very basic thermal polymerization method, and the resultant nitrogen deficient g-C3N4(g-C3N4-1.0) prepared by adding 1 g NaOH exhibited better activity than original g-C3N4for tetracycline degradation, because of a lower recombination rate of photo-excited charge carriers and a redshift of the light absorption range. The advances were confirmed by experiments and spin-polarized density functional theory (DFT), which corroborated each other and showed the effect of defect sites on g-C3N4-1.0 by investigating the electronic structure evolution of the system. The sample can be used for tetracycline degradation, and the spin-polarized DFT study helps understand the reaction mechanism.

Pyrite FeS2has long been a research focus as the alternative anode of rechargeable Ni–Fe cells owing to its eye-catching merits of great earth-abundance, attractive electrical conductivity, and output capacity. However, its further progress is impeded by unsatisfactory cyclic behaviors due to still “ill-defined” phase changes. To gain insights into the pyrite working principles/failure factors, we herein design a core–shell hybrid of a FeS2@carbon nanoreactor, an optimal anode configuration approaching the practical usage state. The resultant electrodes exhibit a Max. specific capacity of ∼272.89 mAh g–1(at ∼0.81 A g–1), remarkably improved cyclic longevity/stability (beyond ∼80% capacity retention after 103cycles) and superior rate capability (∼146.18 mAh g–1is remained at ∼20.01 A g–1) in contrast to bare FeS2counterparts. The as-built Ni–Fe full cells can also output impressive specific energy/power densities of ∼87.38 Wh kg–1/ ∼ 11.54 kW kg–1. Moreover, a refreshed redox reaction working mechanism of “FeS2OH ↔FeS2↔Fe0(in pyrite domains)” is redefined based on real-time electrode characterizations at distinct operation stages. In a total cyclic period, the configured pyrite-based anodes would stepwise undergo three critical stages nominally named “retention”, “phase transition/coexistence”, and “degradation”, each of which is closely related to variations on anodic compositions/structures. Combined with optimal electrode configurations and in-depth clarifications on inherent phase conversions, this focus study may guide us to maximize the utilization efficiency of pyrite for all other aqueous electrochemical devices.

The major accomplishment of electrochemical energy-storage devices is closely linked to the advent of state-of-the-art techniques to make optimal electrode systems. Herein, we demonstrate a unique popcorn-inspired strategy to develop all-conductive and highly puffed Fe⊂carbon nanopopcorns as superb anodes for rechargeable Ni/Fe batteries. Temperature-dependent systematic studies show that the nanopopcorn evolution mechanism is governed by typical phase variation from Fe2O3nanospheres to dispersed Fe0nanodebris, whose formation induces catalytic reconstruction/conversion from hydrocarbons to graphitic nanolayers while triggering the explosion-like instant puffing process beyond 700 °C. The as-built Fe⊂carbon hybrids with favorable loosened structures, open-up/enlarged surface areas, and intrinsically conducting nature enable great electrochemical reactivity and cyclic stability (reversible capacity higher than ∼420 mA h g–1in all cycles without obvious capacity decay), as well as outstanding rate behaviors (∼300 mA h g–1is still retained at ∼20 A g–1). Full-cell devices of NiO@carbon (+)//Fe⊂carbon (−) can exhibit Max. energy/power densities of up to ∼140.8 W h kg–1and ∼15.6 kW kg–1, respectively. This work sheds a fundamental light on arts to configure puffed electrodes for advanced electrodes in various important applications while holding great promise for high-rate/capacity aqueous rechargeable batteries.

Hair growth starts from hair follicles that reside in dermis, and abnormal hair growth is an early sign of hair follicle disease or systemic illness such as alopecia or hair loss. Therefore, identifying a target critical for dysfunctional hair follicles is fundamental to alleviating dermatologic or systemic diseases with hair abnormalities. The warm temperature–activated Ca2+-permeable transient receptor potential vanilloid 3 (TRPV3) channel protein is abundantly expressed in the skin keratinocytes, and dysfunctional TRPV3 causes human congenital Olmsted syndrome, characterized by skin diseases and alopecia, indicating an important role for TRPV3 in hair follicle development and hair growth. To validate TRPV3 as a therapeutic target, we investigated the impact of pharmacological modulation of TRPV3 on hair growth using a combination of biochemical and cell biology, immunohistochemical, whole-cell patch clamp, RNA interference, and pharmacological approaches. We found that functional TRPV3 channel proteins are highly expressed in hair follicle outer root sheath (ORS) cells as detected by Western blot analysis, immunohistochemical staining, and electrophysiological techniques. Pharmacological activation of TRPV3 by agonist natural carvacrol induces cell death of ORS cells, and topical application of carvacrol to mouse dorsal skin also inhibits hair growth. Conversely, specific inhibition of TRPV3 by inhibitor natural forsythoside B and short-hairpin RNA reverses the cell death induced by carvacrol-mediated TRPV3 activation in human ORS cells. Furthermore, forsythoside B results in a significant reversal of hair growth inhibition induced by agonist carvacrol. Altogether, our findings demonstrate that TRPV3 channel is critical for regulation of hair growth, and inhibition of TRPV3 may represent a promising therapy for hair loss or hair follicle–related skin diseases.

Li–S batteries have triggered global research interest because of their higher theoretical energy density and lower cost than popularized Li-ion cells. However, they still do not have practical implementations because of issues induced by intermediate polysulfide dissolution. To better confine both S and polysulfides in cathode regions and prolong the cyclic lifespan, we purposely design the unique highly puffed Co9S8/carbon nanofibers (Co9S8@CNFs) as efficient S carriers. Such fibrous products made of interconnected hollow/porous Co9S8/C nanopolyhedra can provide ample places to load the large amount of S, convenient pathways for both Li+and electrons transfer, and extra reversible capacity contribution. Particularly, each individual Co9S8subunit is physically robust, metallic, and polarized, synergistically enabling the spatial confinement and chemical bonding to restrict S volume expansions and anchor the soluble polysulfides during cycling. The as-built highly puffed S⊆Co9S8@CNFs cathodes can exhibit a large specific capacity of ∼1080 mA h g–1, admirable cyclic stability/lifespan (capacity loss rate: ∼0.03% per cycle), and excellent rate capabilities. Our work may hold a great potential in rational design of superior cathodes for applicable Li–S cell systems.

The human ether-a-go-go-related gene (hERG) encodes the K+channel that carries the rapid component of the delayed rectifier current in the human heart. Reduction of hERG activity induced by gene mutations or pharmacological inhibition is responsible for the type 2 form of long QT syndrome in patients which can develop into ventricular arrhythmia and sudden cardiac death. Therefore, pharmacological activation of hERG may lead to therapeutic potential for cardiac arrhythmias. In this study we characterized a small and novel compound, N-(2-(tert-butyl)phenyl)-6-(4-chlorophenyl)-4-(trifluoromethyl) nicotinamide, HW-0168, that exhibits potent activation of hERG channel with an EC50of 0.41 ± 0.2 μM. Using whole-cell patch clamp recording of HEK293 cells stably expressed hERG channels, we found that HW-0168 dramatically increased current amplitude about 2.5 folds and slowed down current inactivation about 4 folds. HW-0168 shifted the voltage-dependent channel activation to hyperpolarizing direction about 3.7 mV and the voltage-dependent channel inactivation to depolarizing direction about 9.4 mV. In addition, recording of guinea-pig ventricular cells confirmed that HW-0168 shortened the action potential duration. In conclusion, we identified a novel hERG channel activator HW-0168 that can be used for studying the physiological role of hERG in cardiac myocytes and may be beneficial for treating long QT syndrome.

Multiple types of mediastinal masses, especially masses in the anterior mediastinum, may be encountered in routine echocardiographic examinations for symptomatic or asymptomatic patients. The aim of this study was to evaluate the diagnostic value of transthoracic echocardiography combined with contrast‐enhanced ultrasonography in determining the location, composition, and vascularization of mediastinal masses. A retrospective analysis was conducted on 48 consecutive patients who first had a diagnosis of mediastinal masses by echocardiography. The location of the mass, tissue components, and relationships with the heart and great vessels were analyzed on the basis of multiple transthoracic echocardiographic views. Further contrast‐enhanced ultrasonography was performed to determine the vascularization of masses in 25 patients. The clinical, computed tomographic, and histopathologic findings were all recorded and analyzed. The localization, ultrasonographic characteristics of the mass, degree of vascularization, and relationships with the heart and great vessels assessed on echocardiography allowed a correct diagnosis in most of the cases. Transthoracic echocardiography is a useful method for diagnosing mediastinal. Further contrast‐enhanced ultrasonography could provide more details on the degree of vascularization, which could facilitate accurate diagnosis and differentiation diagnosis.

Apical hypertrophic cardiomyopathy (ApHCM) is a unique disease with pathological hypertrophy mainly at the left ventricular (LV) apex. Although previous studies have indicated apical dysfunction in ApHCM, how apical mechanics change during disease progression has not been thoroughly examined. We aimed to characterize the mechanics of the LV apex in ApHCM patients at different disease stages and explore the clinical significance of these alterations.

Enhancing α7 nAChR function serves as a therapeutic strategy for cognitive disorders. Here, we report the synthesis and evaluation of 2-arylamino-thiazole-5-carboxylic acid amide derivatives 6–9that as positive allosteric modulators (PAMs) activate human α7 nAChR current expressed in Xenopusooctyes. Among the 4-amino derivatives, a representative atypical type I PAM 6pexhibits potent activation of α7 current with an EC50of 1.3 μM and the maximum activation effect on the current over 48-fold in the presence of acetylcholine (100 μM). The structure–activity relationship (SAR) analysis reveals that the 4-amino group is crucial for the allosteric activation of α7 currents by compound 6pas the substitution of 4-methyl group results in its conversion to compound 7b(EC50= 2.1 μM; max effect: 58-fold) characterized as a typical type I PAM. Furthermore, both 6pand 7bare able to rescue auditory gating deficits in mouse schizophrenia-like model of acoustic startle prepulse inhibition.

Manganese sulfide (MnS) has triggered great interest as an anode material for rechargeable Li-ion/Na-ion batteries (LIBs/SIBs) because of its low cost, high electrochemical activity, and theoretical capacity. Nevertheless, the practical application is greatly hindered by its rapid capacity decay lead by inevitable active dissolutions and volume expansions in charge/discharge cycles. To resolve the above issues in LIBs/SIBs, we herein put forward the smart construction of MnS nanowires embedded in carbon nanoreactors (MnS@C NWs) via a facile solution method followed by a scalable in situ sulfuration treatment. This engineering protocol toward electrode architectures/configurations endows integrated MnS@C NWs anodes with large specific capacity (with a maximum value of 847 mA h g–1in LIBs and 720 mA h g–1in SIBs), good operation stability, excellent rate capabilities, and prolonged cyclic life span. To prove their potential real applications, we have established the full cells (for LIBs, MnS@C//LiFePO4; for SIBs, MnS@C//Na3V2(PO4)3), both of which are capable of showing remarkable specific capacities, outstanding rate performance, and superb cyclic endurance. This work offers a scalable, simple, and efficient evolution method to produce the integrated hybrid of MnS@C NWs, providing useful inspiration/guidelines for anodic applications of metal sulfides in next-generation power sources.

Practical utilization of silicon (Si) for Li-ion batteries (LIBs) still remains sluggish because of its formidable kinetic problems of huge volume expansions over 300%, instable solid electrolyte interphase (SEI), and unsatisfactory electrical conductivity. Though using a yolk–shell (Y–S) Si@C nanodesign indeed helps to mitigate active changes, optimize SEI properties, and lower intrinsic charge-transfer impedances, the total anodic behaviors in reversibility, rate capabilities, and long-lasting cyclability are still far from perfect. To settle the above issues, we herein propose a reliable and effective way by putting tough and malleable Ni nanoarmors on Y–S Si@C nanoparticles (Si@C⊆Ni). The unique functionalized configurations endow such hybrid systems with superb reversible capacity retention (almost no capacity decay emerges in 600 cycles, retaining a reversible capacity beyond ∼1307 mA h g–1), prominent cyclic stability, and rate behaviors. To justify their potential usage, full cells of (−)Si@C⊆Ni//LiFePO4(+) are further constructed, delivering impressive specific energy and power densities (max. values: ∼423 W h kg–1/∼497.8 W kg–1). This paradigm work may offer a highly feasible engineering protocol to push forward Si anode performances for next-generation LIBs.

Multitarget antidepressants selectively inhibiting monoaminergic transporters and 5-hydroxytryptamine (5-HT) 2A receptor have demonstrated higher efficacy and fewer side effects than selective serotonin reuptake inhibitors. In the present study, we synthesized a series of novel 3-(benzo[d][1,3]dioxol-4-yloxy)-3-arylpropyl amine derivatives, among which compound H05 was identified as a lead, exhibiting potent inhibitory effects on both serotonin (Ki= 4.81 nM) and norepinephrine (NE) (Ki= 6.72 nM) transporters and moderate 5-HT2Aantagonist activity (IC50= 60.37 nM). H05 was able to dose-dependently reduce the immobility duration in mouse forced swimming test and tail suspension test, with the minimal effective doses lower than those of duloxetine, and showed no stimulatory effect on locomotor activity. The administration of H05 (5, 10, and 20 mg/kg, by mouth) significantly shortened the immobility time of adrenocorticotropin-treated rats that serve as a model of treatment-resistant depression, whereas imipramine (30 mg/kg, by mouth) and duloxetine (30 mg/kg, by mouth) showed no obvious effects. Chronic treatment with H05 reversed the depressive-like behaviors in a rat model of chronic unpredictable mild stress and a mouse model of corticosterone-induced depression. Microdialysis analysis revealed that the administration of H05 at either 10 or 20 mg/kg increased the release of 5-HT and NE from the frontal cortex. The pharmacokinetic (PK) and brain penetration analyses suggest that H05 has favorable PK properties with good blood-brain penetration ability. Therefore, it can be concluded that H05, a novel serotonin and NE reuptake inhibitor with 5-HT2Aantagonist activity, possesses efficacious activity in the preclinical models of depression and treatment-resistant depression, and it may warrant further evaluation for clinical development.

Exploring stable two-dimensional materials with appropriate band gaps and high carrier mobility is highly desirable due to the potential applications in optoelectronic devices. Here, the electronic structures of phosphorene on a Au(111) substrate are investigated by scanning tunneling spectroscopy, angle-resolved photoemission spectroscopy (ARPES), and density functional theory (DFT) calculations. The substrate-induced phosphorene superstructure gives a superlattice potential, leading to a strong band folding effect of the sp band of Au(111) on the band structure. The band gap could be clearly identified in the ARPES results after examining the folded sp band. The value of the energy gap (∼1.1 eV) and the high charge carrier mobility comparable to that of black phosphorus, which is engineered by the tensile strain, are revealed by the combination of ARPES results and DFT calculations. Furthermore, the phosphorene layer on the Au(111) surface displays high surface inertness, leading to the absence of multilayer phosphorene. All these results suggest that the phosphorene on Au(111) could be a promising candidate, not only for fundamental research but also for nanoelectronic and optoelectronic applications.

Two-dimensional (2D) group IV elemental materials are expected to have similar electronic features to their lightest analogue, graphene. The favorable hybridization state of heavier group IV elements is the sp3state, leading to buckled structures instead of a planar one. These buckled structures could modulate the vibrational properties of these 2D materials by introducing a strain effect. In this review, the authors focus on the recent research on the Raman spectra of silicene and germanene from both the theoretical and experimental sides. The abundant superstructures of silicene and germanene are formed due to the different interaction strengths between silicene/germanene and underlying substrate, providing a way to modulate their phonon vibrational properties. Several factors affecting the vibrational modes are discussed, including the strain, doping, coverage and defect effects. Furthermore, the relationship between electron–phonon coupling strength and these factors is established based on the variation of Raman peak position and linewidth. Finally, the authors provide an overview of the general outlook and challenges for this field.