Modified EBP-bFGF targeting endogenous renal extracellular matrix protects against renal ischemia-reperfusion injury in rats.

Acute kidney injury (AKI) is a life-threatening disease primarily caused by renal ischemia-reperfusion (I/R) injury, which can result in renal failure. Currently, growth factor therapy is considered a promising and effective approach for AKI treatment. Basic fibroblast growth factor (bFGF), an angiogenic factor with potent activity, efficiently stimulates angiogenesis and facilitates regeneration of renal tissue. However, the unrestricted diffusion of bFGF restricts its clinical application in AKI treatment. Therefore, developing a novel sustained released system for bFGF could enhance its potential in treating AKI. In this study, we genetically engineered a multifunctional recombinant protein by fusing bFGF with a specific peptide (EBP). EBP-bFGF effectively binds to the extracellular matrix in the injured kidney, enabling slow release of bFGF in AKI. Furthermore, following orthotopic injection into I/R rats' ischemic kidneys, EBP-bFGF exhibited stable retention within the tissue. Additionally, EBP-bFGF suppressed apoptosis of renal cells, reduced renal fibrosis, and facilitated recovery of renal function. These findings suggest that EBP-bFGF delivery system represents a promising strategy for treating AKI.

Identification of odorant-binding proteins and functional analysis of antenna-specific BhorOBP28 in Batocera horsfieldi (Hope).

BACKGROUND: The important wood-boring pest Batocera horsfieldi has evolved a sensitive olfactory system to locate host plants. Odorant-binding proteins (OBPs) are thought to play key roles in olfactory recognition. Therefore, exploring the physiological function of OBPs could facilitate a better understanding of insect chemical communications. RESULTS: In this research, 36 BhorOBPs genes were identified via transcriptome sequencing of adults' antennae from B. horsfieldi, and most BhorOBPs were predominantly expressed in chemosensory body parts. Through fluorescence competitive binding and fluorescence quenching assays, the antenna-specific BhorOBP28 was investigated and displayed strong binding affinities forming stable complexes with five volatiles, including (+)-α-Pinene, (+)-Limonene, ß-Pinene, (-)-Limonene, and (+)-Longifolene, which could also elicit conformation changes when they were interacting with BhorOBP28. Batocera horsfieldi females exhibited a preference for (-)-Limonene, and a repellent response to (+)-Longifolene. Feeding dsOBP19 produced by a bacteria-expressed system with a newly constructed vector could lead to the knockdown of BhorOBP28, and could further impair B. horsfieldi attraction to (-)-Limonene and repellent activity of (+)-Longifolene. The analysis of site-directed mutagenesis revealed that Leu7, Leu72, and Phe121 play a vital role in selectively binding properties of BhorOBP28. CONCLUSION: By modeling the molecular mechanism of olfactory recognition, these results demonstrate that BhorOBP28 is involved in the chemoreception of B. horsfieldi. The bacterial-expressed dsRNA delivery system gains new insights into potential population management strategies. Through the olfactory process concluded that discovering novel behavioral regulation and environmentally friendly control options for B. horsfieldi in the future. © 2024 Society of Chemical Industry.

Origin and evolution of pentanucleotide repeat expansions at the familial cortical myoclonic tremor with epilepsy type1 - SAMD12 locus.

Familial cortical myoclonic tremor with epilepsy type 1 (FCMTE1) is caused by (TTTTA)exp(TTTCA)exp repeat expansions in SAMD12, while pure (TTTTA)exp is polymorphic. Our investigation focused on the origin and evolution of pure (TTTTA)exp and (TTTTA)exp(TTTCA)exp at this locus. We observed a founder effect between them. The phylogenetic analysis suggested that the (TTTTA)exp(TTTCA)exp might be generated from pure (TTTTA)exp through infrequent transformation events. Long-read sequencing revealed somatic generation of (TTTTA)exp(TTTCA)exp from pure (TTTTA)exp, likely via long segment (TTTCA) repeats insertion. Our findings indicate close relationships between the non-pathogenic (TTTTA)exp and the pathogenic (TTTTA)exp(TTTCA)exp, with dynamic interconversions. This sheds light on the genesis of pathogenic repeat expansions from ancestral premutation alleles. Our results may guide future studies in detecting novel repeat expansion disorders and elucidating repeat expansion mutational processes, thereby enhancing our understanding of human genomic variation.

Laser Shock Peening: Fundamentals and Mechanisms of Metallic Material Wear Resistance Improvement.

With the rapid development of the advanced manufacturing industry, equipment requirements are becoming increasingly stringent. Since metallic materials often present failure problems resulting from wear due to extreme service conditions, researchers have developed various methods to improve their properties. Laser shock peening (LSP) is a highly efficacious mechanical surface modification technique utilized to enhance the microstructure of the near-surface layer of metallic materials, which improves mechanical properties such as wear resistance and solves failure problems. In this work, we summarize the fundamental principles of LSP and laser-induced plasma shock waves, along with the development of this technique. In addition, exemplary cases of LSP treatment used for wear resistance improvement in metallic materials of various nature, including conventional metallic materials, laser additively manufactured parts, and laser cladding coatings, are outlined in detail. We further discuss the mechanism by which the microhardness enhancement, grain refinement, and beneficial residual stress are imparted to metallic materials by using LSP treatment, resulting in a significant improvement in wear resistance. This work serves as an important reference for researchers to further explore the fundamentals and the metallic material wear resistance enhancement mechanism of LSP.

Dysphagia Pattern in Early to Moderate Parkinson's Disease Caused by Abnormal Pharyngeal Kinematic Function.

Airway invasion is common in patients with Parkinson's disease (PD) and can cause serious complications. However, a PD-related dysphagic pattern has not been clearly elucidated. In this study, 53 patients with early to moderate PD were enrolled to undergo a videofluoroscopic study of swallowing evaluation (VFSS) and a battery of neuropsychological assessments. A set of VFSS variables (three visuoperceptual, nine temporal, and six spatial) were measured. The main effects of bolus viscosity and volume on airway invasion were calculated. Statistical analyses were performed to determine key kinematic factors of airway invasion for swallowing each bolus type. Airway invasion frequency was significantly higher for liquid boluses (liquid vs. pudding P < 0.001; liquid vs. honey P = 0.006). Laryngeal vestibule closure reaction time (LVCrt) was the key kinematic factor of airway invasion for 3 ml liquid swallow (P = 0.040), anterior displacement of hyoid bone was the key kinematic factor for both 5 ml and 10 ml liquid swallows (P = 0.010, 0.034, respectively). Male sex and advanced Hoehn and Yahr stage were significantly related to reduced anterior displacement of hyoid bone. These results reveal the dysphagic pattern related to PD, demonstrating that prolonged LVCrt and reduced anterior displacement of hyoid bone are two crucial kinematic factors contributing to airway invasion during the liquid swallow. In addition, hyoid bone dysfunction was correlated with disease severity and male sex. Our findings warrant further investigation of the pathophysiological mechanism of dysphagia in PD and would guide clinical intervention.

Magnetic resonance imaging-based approaches for detecting the efficacy of combining therapy following VEGFR-2 and PD-1 blockade in a colon cancer model.

BACKGROUND: Angiogenesis inhibitors have been identified to improve the efficacy of immunotherapy in recent studies. However, the delayed therapeutic effect of immunotherapy poses challenges in treatment planning. Therefore, this study aims to explore the potential of non-invasive imaging techniques, specifically intravoxel-incoherent-motion diffusion-weighted imaging (IVIM-DWI) and blood oxygenation level-dependent magnetic resonance imaging (BOLD-MRI), in detecting the anti-tumor response to the combination therapy involving immune checkpoint blockade therapy and anti-angiogenesis therapy in a tumor-bearing animal model. METHODS: The C57BL/6 mice were implanted with murine MC-38 cells to establish colon cancer xenograft model, and randomly divided into the control group, anti-PD-1 therapy group, and combination therapy group (VEGFR-2 inhibitor combined with anti-PD-1 antibody treatment). All mice were imaged before and, on the 3rd, 6th, 9th, and 12th day after administration, and pathological examinations were conducted at the same time points. RESULTS: The combination therapy group effectively suppressed tumor growth, exhibiting a significantly higher tumor inhibition rate of 69.96% compared to the anti-PD-1 group (56.71%). The f value and D* value of IVIM-DWI exhibit advantages in reflecting tumor angiogenesis. The D* value showed the highest correlation with CD31 (r = 0.702, P = 0.001), and the f value demonstrated the closest correlation with vessel maturity (r = 0.693, P = 0.001). While the BOLD-MRI parameter, R2* value, shows the highest correlation with Hif-1α(r = 0.778, P < 0.001), indicating the capability of BOLD-MRI to evaluate tumor hypoxia. In addition, the D value of IVIM-DWI is closely related to tumor cell proliferation, apoptosis, and infiltration of lymphocytes. The D value was highly correlated with Ki-67 (r = - 0.792, P < 0.001), TUNEL (r = 0.910, P < 0.001) and CD8a (r = 0.918, P < 0.001). CONCLUSIONS: The combination of VEGFR-2 inhibitors with PD-1 immunotherapy shows a synergistic anti-tumor effect on the mouse colon cancer model. IVIM-DWI and BOLD-MRI are expected to be used as non-invasive approaches to provide imaging-based evidence for tumor response detection and efficacy evaluation.

Seizures and electrophysiological features in familial cortical myoclonic tremor with epilepsy 1.

OBJECTIVES: To investigate and characterize epileptic seizures and electrophysiological features of familial cortical myoclonic tremor with epilepsy (FCMTE) type 1 patients in a large Chinese cohort. METHODS: We systematically evaluated 125 FCMTEtype 1 patients carrying the pentanucleotide (TTTCA) repeat expansion in the SAMD12 gene in China. RESULTS: Among the 28 probands, epileptic seizures (96.4%, 27/28) were the most common reason for an initial clinic visit. Ninety-seven (77.6%, 97/125) patients had experienced seizures. The seizures onset age was 36.5 ± 9.0 years, which was 6.9 years later than cortical tremors. The seizures were largely rare (<1/year, 58.8%) and occasional (1-6/year, 37.1%). Prolonged prodromes were reported in 57.7% (56/97). Thirty-one patients (24.8%, 31/125) reported photosensitivity history, and 79.5% (31/39) had a photoparoxysmal response. Interictal epileptiform discharges (IEDs) were recorded in 69.1% (56/81) of patients. Thirty-three patients showed generalized IEDs and 72.7% (24/33) were occipitally dominant, while 23 patients presented with focal IEDs with 65.2% (15/23) taking place over the occipital lobe. Overnight EEG of FCMTE patients displayed paradoxical sleep-wake fluctuation, with a higher average IED index of 0.82 ± 0.88/min during wakefulness and a lower IED index of 0.04 ± 0.06/min during non-rapid eye movement sleep stages I-II. INTERPRETATION: FCMTE type 1 has a benign course of epilepsy and distinct clinical and electrophysiological features. In addition to a positive family history and cortical myoclonus tremor, the seizure prodromes, specific seizure triggers, photosensitivity, distribution of IEDs, and unique fluctuations during sleep-wake cycle are cues for proper genetic testing and an early diagnosis of FCMTE.

Retinal Thinning as a Marker of Disease Severity in Progressive Supranuclear Palsy.

OBJECTIVE: Progressive supranuclear palsy (PSP) involves a variety of visual symptoms that are thought to be partially caused by structural abnormalities of the retina. However, the relationship between retinal structural changes, disease severity, and intracranial alterations remains unknown. We investigated distinct retinal thinning patterns and their relationship with clinical severity and intracranial alterations in a PSP cohort. METHODS: We enrolled 19 patients with PSP (38 eyes) and 20 age-matched healthy controls (40 eyes). All of the participants underwent peripapillary and macular optical coherence tomography. Brain 11C-2ß-carbomethoxy-3ß-(4-fluorophenyl) tropane (11C-CFT) and 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography imaging were also performed in patients with PSP. We investigated the association between retinal thickness changes and clinical features, striatal dopamine transporter availability, and cerebral glucose metabolism. RESULTS: The peripapillary retinal nerve fiber layer (pRNFL) and macula were significantly thinner in patients with PSP than in controls. The thickness of the superior sector of the pRNFL demonstrated a significant negative relationship with the Movement Disorder Society-Unified Parkinson's Disease Rating Scale part III and Hoehn and Yahr staging scale scores. A significant negative correlation was found between outer inferior macular thickness and disease duration. Outer temporal macular thickness was positively correlated with Montreal Cognitive Assessment scores. In PSP, lower outer temporal macular thickness was also positively correlated with decreased dopamine transporter binding in the caudate. CONCLUSION: The pRNFL and macular thinning may be candidate markers for monitoring disease severity. Additionally, macular thinning may be an in vivo indicator of nigrostriatal dopaminergic cell degeneration in PSP patients.

TFIIB-Related Protein BRP5/PTF2 Is Required for Both Male and Female Gametogenesis and for Grain Formation in Rice.

Transcription factor IIB (TFIIB) is a general transcription factor for RNA polymerase II, exerting its influence across various biological contexts. In the majority of eukaryotes, TFIIB typically has two homologs, serving as general transcription factors for RNA polymerase I and III. In plants, however, the TFIIB-related protein family has expanded greatly, with 14 and 9 members in Arabidopsis and rice, respectively. BRP5/pollen-expressed transcription factor 2 (PTF2) proteins belong to a subfamily of TFIIB-related proteins found only in plants and algae. The prior analysis of an Arabidopsis atbrp5 mutant, characterized by a T-DNA insertion at the 5' untranslated region, demonstrated the essential role of BRP5/PTF2 during the process of pollen germination and embryogenesis in Arabidopsis. Using a rice transformation system based on CRISPR/Cas9 technology, we have generated transgenic rice plants containing loss-of-function frameshift mutations in the BRP5/PTF2 gene. Unlike in the Arabidopsis atbrp5 mutant, the brp5/ptf2 frameshift mutations were not transmitted to progeny in rice, indicating an essential role of BRP5/PTF2 in both male and female gamete development or viability. The silencing of rice BRP5/PTF2 expression through RNA interference (RNAi) had little effect on vegetative growth and panicle formation but strongly affected pollen development and grain formation. Genetic analysis revealed that strong RNAi silencing of rice BRP5/PTF2 was still transmissible to progeny almost exclusively through female gametes, as found in the Arabidopsis atbrp5 knockdown mutant. Thus, reduced rice BRP5/PTF2 expression impacted pollen preferentially by interfering with male gamete development or viability. Drawing upon these findings, we posit that BRP5/PTF2 assumes a distinct and imperative function in the realm of plant sexual reproduction.

Generation of an induced pluripotent stem cell line (ZJUi013-A) from a Familial cortical myoclonic tremor with epilepsy type 1 patient carrying (TTTCA)n insertion in the SAMD12 gene.

FCMTE1 is an autosomal dominant inherited neurodegenerative disorder characterized by myoclonic tremors and epilepsy. The cause of FCMTE1 is an abnormal (TTTCA)n insertion in intron 4 of SAMD12 gene. Fibroblasts obtained from a FCMTE1 patient were successfully transformed into induced pluripotent stem cells (iPSCs) (ZJUi013-A) using the Sendai virus. Our approach provided a resource for further pathogenesis study and drug screening of FCMTE1.

In vitro knockdown of TsDNase II-7 suppresses Trichinella spiralis invasion into the host's intestinal epithelial cells.

Trichinella spiralis (T. spiralis) adult-specific deoxyribonuclease II-7 (TsDNase II-7), a member of the DNase II-like nuclease family with no DNase II activity, was identified in the excretory-secretory (ES) products of adult worms (AWs). However, its biological functions are still unclear. Our previous study revealed that TsDNase II-7 is located around the infection site in the intestinal tissue, speculating that it was involved in the T. spiralis invasion of host intestinal epithelial cells (IECs). This study aimed to use RNA interference to verify our speculation that TsDNase II-7 in 3-day old adult T. spiralis (Ad3) plays a role in intestinal invasion. TsDNase II-7-specific small interfering RNAs (siRNAs) were delivered into muscle larvae (MLs) to knockdown TsDNase II-7 expression by electroporation. Twenty-four hours later, the MLs transfected with 2 µM siRNA-841 exhibited decreased in TsDNase II-7 transcription and expression as compared to the control MLs. The knockdown of TsDNase II-7 expression did not affect ML viability, and the low expression of TsDNase II-7 still maintained in Ad3 recovered from TsDNase II-7-RNAi-ML infected mice, resulting in a weakened ability of Ad3 to invade intestinal epithelial cells (IECs). These results indicated that knockdown of TsDNase II-7 gene expression via RNA interference (RNAi) suppressed adult worm invasion and confirmed that TsDNase II-7 plays a crucial role during the intestinal phase of T. spiralis infections, which provided new candidate for vaccine development of T. spiralis.

Monodispersed MOF-Modified Nanofibers as Versatile Building Blocks for the Ion Regulations in Safe Lithium-Sulfur Batteries.

Lithium-sulfur battery is the most promising candidate for the next generation of rechargeable batteries because of the high energy density. However, the severe shuttle effect of lithium polysulfides (LiPSs) and degradation of the lithium anode during cycling are significant issues that hinder the practical application of lithium-sulfur batteries. Herein, monodispersed metal-organic framework (MOF)-modified nanofibers are prepared as building blocks to construct both a separator and a composite polymer electrolyte in lithium-sulfur systems. This building block possesses the intrinsic advantages of good mechanical properties, thermal stability, and good electrolyte affinity. MOFs, grown continuously on the monodispersed nanofibers, can effectively adsorb LiPSs and play a key role in regulating the nucleation and stripping/plating process of the lithium anode. When assembled into the separator, the symmetric battery remains stable for 2500 h at a current density of 1 mA cm-2, and the lithium-sulfur full cell shows improved electrochemical performance. In order to improve the safety property, the composite polymer electrolyte is prepared with the MOF-modified nanofiber as the filler. The quasi-solid-state symmetric battery remains stable for 3000 h at a current density of 0.1 mA cm-2, and the corresponding lithium-sulfur cell can cycle 800 times at 1 C with a capacity decay rate of only 0.038% per cycle.

K235 acetylation couples with PSPC1 to regulate the m6A demethylation activity of ALKBH5 and tumorigenesis.

N6-methyladenosine (m6A) modification plays important roles in bioprocesses and diseases. AlkB homolog 5 (ALKBH5) is one of two m6A demethylases. Here, we reveal that ALKBH5 is acetylated at lysine 235 (K235) by lysine acetyltransferase 8 and deacetylated by histone deacetylase 7. K235 acetylation strengthens the m6A demethylation activity of ALKBH5 by increasing its recognition of m6A on mRNA. RNA-binding protein paraspeckle component 1 (PSCP1) is a regulatory subunit of ALKBH5 and preferentially interacts with K235-acetylated ALKBH5 to recruit and facilitate the recognition of m6A mRNA by ALKBH5, thereby promoting m6A erasure. Mitogenic signals promote ALKBH5 K235 acetylation. K235 acetylation of ALKBH5 is upregulated in cancers and promotes tumorigenesis. Thus, our findings reveal that the m6A demethylation activity of ALKBH5 is orchestrated by its K235 acetylation and regulatory subunit PSPC1 and that K235 acetylation is necessary for the m6A demethylase activity and oncogenic roles of ALKBH5.

Non-coding RNAs regulating mitochondrial function in cardiovascular diseases.

Cardiovascular disease (CVD) is the leading cause of disease-related death worldwide and a significant obstacle to improving patients' health and lives. Mitochondria are core organelles for the maintenance of myocardial tissue homeostasis, and their impairment and dysfunction are considered major contributors to the pathogenesis of various CVDs, such as hypertension, myocardial infarction, and heart failure. However, the exact roles of mitochondrial dysfunction involved in CVD pathogenesis remain not fully understood. Non-coding RNAs (ncRNAs), particularly microRNAs, long non-coding RNAs, and circular RNAs, have been shown to be crucial regulators in the initiation and development of CVDs. They can participate in CVD progression by impacting mitochondria and regulating mitochondrial function-related genes and signaling pathways. Some ncRNAs also exhibit great potential as diagnostic and/or prognostic biomarkers as well as therapeutic targets for CVD patients. In this review, we mainly focus on the underlying mechanisms of ncRNAs involved in the regulation of mitochondrial functions and their role in CVD progression. We also highlight their clinical implications as biomarkers for diagnosis and prognosis in CVD treatment. The information reviewed herein could be extremely beneficial to the development of ncRNA-based therapeutic strategies for CVD patients.

Organic Memristor with Synaptic Plasticity for Neuromorphic Computing Applications.

Memristors have been considered to be more efficient than traditional Complementary Metal Oxide Semiconductor (CMOS) devices in implementing artificial synapses, which are fundamental yet very critical components of neurons as well as neural networks. Compared with inorganic counterparts, organic memristors have many advantages, including low-cost, easy manufacture, high mechanical flexibility, and biocompatibility, making them applicable in more scenarios. Here, we present an organic memristor based on an ethyl viologen diperchlorate [EV(ClO4)]2/triphenylamine-containing polymer (BTPA-F) redox system. The device with bilayer structure organic materials as the resistive switching layer (RSL) exhibits memristive behaviors and excellent long-term synaptic plasticity. Additionally, the device's conductance states can be precisely modulated by consecutively applying voltage pulses between the top and bottom electrodes. A three-layer perception neural network with in situ computing enabled was then constructed utilizing the proposed memristor and trained on the basis of the device's synaptic plasticity characteristics and conductance modulation rules. Recognition accuracies of 97.3% and 90% were achieved, respectively, for the raw and 20% noisy handwritten digits images from the Modified National Institute of Standards and Technology (MNIST) dataset, demonstrating the feasibility and applicability of implementing neuromorphic computing applications utilizing the proposed organic memristor.

[Treatment of stable degenerative lumbar spondylolisthesis with percutaneous endoscopic surgery through two different approaches].

OBJECTIVE: To assess the clinical effects of percutaneous endoscopic surgery through two different approaches for stable degenerative lumbar spondylolisthesis. METHODS: Sixty-four patients with stable degenerative lumbar spondylolisthesis who underwent percutaneous endoscopic procedures between January 2016 and December 2019 were divided into transforaminal approach group and interlaminar approach group according to surgical approaches, 32 patients in each group. There were 16 males and 16 females in transforaminal approach group, aged from 52 to 84 years old with an average of (66.03±9.60) years, L2 slippage in 4 cases, L3 slippage in 5, and L4 slippage in 23. There were 17 males and 15 females in interlaminar approach group, aged from 46 to 81 years old with an average of (61.38±9.88) years, L3 slippage in 3 cases, L4 slippage in 15, and L5 slippage in 14. Operative time, intraoperative fluoroscopy times, and postoperative bedtime were compared between two groups. Anteroposterior displacement values, interbody opening angles, and the percentage of slippage were measured on preoperative and postoperative 12-month dynamic radiographs. Visual analogue scale (VAS) of low back pain and lower extremity pain, and the Japanese Orthopaedic Association (JOA) score before and after surgery were observed, and clinical effects were evaluated according to the modified MACNAB criteria. RESULTS: All operations were successfully completed, and patients in both groups were followed up for more than 1 year, and without complications during follow-up period. ①There was no significant difference in operation time between two groups(P>0.05). Intraoperative fluoroscopy times were longer in transforaminal approach group than that in intervertebral approach group(P<0.05). Postoperative bedtime was shorter in transforaminal approach group than that in intervertebral approach group (P<0.05).② No lumbar instability was found on dynamic radiography at 12 months postoperatively in both groups. There were no significant differences in anteroposterior displacement values, interbody opening angles, and the percentage of slippage between two groups postoperative 12 months and preoperative 1 day(P>0.05). ③There was no significant difference between two groups in VAS of low back pain at 3 days and 1, 12 months after the operation compared with the preoperative(P>0.05), but the VAS of the lower extremity pain was significantly improved compared with the preoperative(P<0.05). Both of groups showed significant improvement in JOA score at 12 months compared with preoperatively(P<0.05). There was no significant difference in VAS of low back pain, lower extremity pain and JOA scores between two groups during the same period after surgery(P>0.05). According to modified Macnab criteria, excellent, good, fair and poor outcomes were 21, 7, 3 and 1 in transforaminal approach group respectively, and which in intervertebral approach group were 20, 7, 5 and 0, there was no significant difference in clinical effect between the groups(P>0.05). CONCLUSION: Intervertebral approach may reduce intraoperative fluoroscopy times and transforaminal approach can shorten postoperative bedtime, both approaches achieve satisfactory results in the treatment of stable degenerative lumbar spondylolisthesis with no progression of short-term slippage.

Ni Single Atoms on MoS2 Nanosheets Enabling Enhanced Kinetics of Li-S Batteries.

The practical application of Li-S batteries is seriously hindered due to its shuttle effect and sluggish redox reaction, which requires a better functional separator to solve the problems. Herein, polypropylene separators modified by MoS2 nanosheets with atomically dispersed nickel (Ni-MoS2 ) are prepared to prevent the shuttle effect and facilitate the redox kinetics for Li-S batteries. Compared with pristine MoS2 nanosheets, Ni-MoS2 nanosheets exhibit both excellent adsorption and catalysis performance for overcoming the shuttle effect. Assembled with this novel separator, the Li-S batteries exhibit an admirable cycling stability at 2 C over 400 cycles with 0.01% per cycle decaying. In addition, even with a high sulfur loading of 7.5 mg cm-2 , the battery still provides an initial capacity of 6.9 mAh cm-2 and remains 5.9 mAh cm-2 after 50 cycles because of the fast convention of polysulfides catalyzed by Ni-MoS2 nanosheets, which is further confirmed by the density functional theory (DFT) calculations. Therefore, the proposed strategy is expected to offer a new thought for single atom catalyst applying in Li-S batteries.

Combination of the STING Agonist MIW815 (ADU-S100) and PD-1 Inhibitor Spartalizumab in Advanced/Metastatic Solid Tumors or Lymphomas: An Open-Label, Multicenter, Phase Ib Study.

PURPOSE: The stimulator of IFN genes (STING) is a transmembrane protein that plays a role in the immune response to tumors. Single-agent STING agonist MIW815 (ADU-S100) has demonstrated immune activation but limited antitumor activity. This phase Ib, multicenter, dose-escalation study assessed the safety and tolerability of MIW815 plus spartalizumab (PDR001), a humanized IgG4 antibody against PD-1, in 106 patients with advanced solid tumors or lymphomas. PATIENTS AND METHODS: Patients were treated with weekly intratumoral injections of MIW815 (50-3,200 µg) on a 3-weeks-on/1-week-off schedule or once every 4 weeks, plus a fixed dose of spartalizumab (400 mg) intravenously every 4 weeks. RESULTS: Common adverse events were pyrexia (n = 23; 22%), injection site pain (n = 21; 20%), and diarrhea (n = 12; 11%). Overall response rate was 10.4%. The MTD was not reached. Pharmacodynamic biomarker analysis demonstrated on-target activity. CONCLUSIONS: The combination of MIW815 and spartalizumab was well tolerated in patients with advanced/metastatic cancers, including in patients with anti-PD-1 refractory disease. Minimal antitumor responses were seen.