•A comprehensive review of researches on PEMFC degradation in start-stop condition.•Include degradation mechanism, accelerated lifetime tests and mitigation solutions.•Further researches should be ...taken from aspects such as material and strategy.
The lifetime of the proton exchange membrane fuel cell (PEMFC) is the main issue restricting its commercialization. During real vehicular applications, the fuel cell engine mainly experiences four dynamic conditions: load changing, start-stop, idling, and high power. Since the start-stop condition has a great impact on the lifetime of fuel cells, it is necessary to fully understand the degradation mechanism of PEMFC under this condition. This paper discusses the background and progresses in related research, analyses the gas distribution process inside the fuel cells during start-stop, and summarises the main mechanism and factors that lead to the degradation. Then, solutions in terms of material improvement and system control are listed. This review can provide a basis for solving the degradation problem in PEMFCs and improving the cell lifetime.
The conformal integration of electronic systems with irregular, soft objects is essential for many emerging technologies. We report the design of van der Waals thin films consisting of staggered ...two-dimensional nanosheets with bond-free van der Waals interfaces. The films feature sliding and rotation degrees of freedom among the staggered nanosheets to ensure mechanical stretchability and malleability, as well as a percolating network of nanochannels to endow permeability and breathability. With an excellent mechanical match to soft biological tissues, the freestanding films can naturally adapt to local surface topographies and seamlessly merge with living organisms with highly conformal interfaces, rendering living organisms with electronic functions, including leaf-gate and skin-gate transistors. On-skin transistors allow high-fidelity monitoring and local amplification of skin potentials and electrophysiological signals.
Two-dimensional (2D) semiconductors have attracted intense interest for their unique photophysical properties, including large exciton binding energies and strong gate tunability, which arise from ...their reduced dimensionality
. Despite considerable efforts, a disconnect persists between the fundamental photophysics in pristine 2D semiconductors and the practical device performances, which are often plagued by many extrinsic factors, including chemical disorder at the semiconductor-contact interface. Here, by using van der Waals contacts with minimal interfacial disorder, we suppress contact-induced Shockley-Read-Hall recombination and realize nearly intrinsic photophysics-dictated device performance in 2D semiconductor diodes. Using an electrostatic field in a split-gate geometry to independently modulate electron and hole doping in tungsten diselenide diodes, we discover an unusual peak in the short-circuit photocurrent at low charge densities. Time-resolved photoluminescence reveals a substantial decrease of the exciton lifetime from around 800 picoseconds in the charge-neutral regime to around 50 picoseconds at high doping densities owing to increased exciton-charge Auger recombination. Taken together, we show that an exciton-diffusion-limited model well explains the charge-density-dependent short-circuit photocurrent, a result further confirmed by scanning photocurrent microscopy. We thus demonstrate the fundamental role of exciton diffusion and two-body exciton-charge Auger recombination in 2D devices and highlight that the intrinsic photophysics of 2D semiconductors can be used to create more efficient optoelectronic devices.
The mechanisms of inflammation in bone and joint tissue are complex and involve long non‑coding RNAs (lncRNAs), which play an important role in this process. The aim of the present study was to ...screen out differentially expressed genes in human osteoblasts stimulated by inflammation, and to further explore the mechanisms underlying inflammatory responses and the functional activity of human osteoblasts through bioinformatics methods and in vitro experiments. For this purpose, MG63 cells were stimulated with various concentrations of lipopolysaccharide (LPS) for different periods of time to construct an optimal inflammatory model and RNA sequencing was then performed on these cells. The levels of nuclear enriched abundant transcript 1 (NEAT1), various inflammatory factors, Nod‑like receptor protein 3 (NLRP3) protein and osteogenesis‑related proteins, as well as the levels of cell apoptosis‑ and cell cycle‑related markers were measured in MG63 cells stimulated with LPS, transfected with NEAT1 overexpression plasmid and treated with bexarotene by western blot analysis, RT‑qPCR, immunofluorescence, FISH, TEM and flow cytometry. There were 427 differentially expressed genes in the LPS‑stimulated MG63 cells, in which NEAT1 was significantly downregulated. LPS upregulated the expression of inflammatory cytokines and NLRP3, inhibited the expression of autophagy‑related and osteogenesis‑related proteins, promoted apoptosis and altered the cell cycle, which was partially inhibited by NEAT1 overexpression and promoted by bexarotene. LPS stimulated inflammation in the MG63 cells and inhibited the retinoid X receptor (RXR)‑α to downregulate the expression of NEAT1 and decrease levels of autophagy, which promoted the activation of NLRP3 and the release of inflammatory factors, and impaired the functional activity of osteoblasts, thus promoting the development of inflammation.
To determine national incidence and risk factors associated with developing endophthalmitis after cataract surgery in the United States.
Retrospective, cross-sectional analysis.
Medicare ...beneficiaries aged ≥65 years undergoing cataract surgery between 2011 and 2019.
Medicare claims were used to identify all patients who underwent ≥1 cataract surgery between 2011 and 2019. Endophthalmitis cases within 90 days of the cataract surgery were identified using diagnostic codes. Patients with a history of endophthalmitis 12 months before their cataract surgery procedure were excluded. Annual and aggregate 9-year incidences were determined for all cataract surgeries and for stand-alone cataract procedures. A stepwise multivariable logistic regression model using generalized estimating equations was used to evaluate factors associated with occurrence of postoperative endophthalmitis.
The 90-day postoperative endophthalmitis rate and patient risk factors associated with onset of endophthalmitis after cataract surgery.
A total of 14 396 438 cataract surgeries were performed among Medicare beneficiaries between 2011 and 2019. The overall 90-day postoperative endophthalmitis rate was 1.36 per 1000 cataract surgeries for all cataract procedures and 1.30 per 1000 cataract surgeries for stand-alone cataract procedures. A decreasing trend was noted for postoperative endophthalmitis rates during the 9-year study period. On multivariable analysis, the risk of endophthalmitis after cataract surgery was increased for cases performed among those aged ≥75 years versus those aged <75 years (odds ratio OR, 1.14; 95% confidence interval CI, 1.11-1.18), Blacks (OR, 1.13; 95% CI, 1.07-1.20), Native Americans (OR, 1.43; 95% CI, 1.19-1.73), and eyes with any history of invasive glaucoma surgery (OR, 1.40; 95% CI, 1.18-1.65). Cataract cases combined with retinal surgery (OR, 2.60; 95% CI, 2.15-3.16) and those performed when the Charlson Comorbidity Index (CCI) was greater than 0 also had an increased likelihood of developing endophthalmitis. The risk of endophthalmitis was lower for cases performed on women versus men (OR, 0.89; 95% CI, 0.86-0.92).
The overall 90-day postoperative endophthalmitis rate after cataract surgery was 1.36 per 1000 cataract surgeries between 2011 and 2019. Patient age, gender, race, and CCI were associated with risk of endophthalmitis.
Poly (ADP-ribose) polymerase-1 (PARP1) is a highly conserved enzyme focused on the self-repair of cellular DNA damage. Until now, numbers of PARP inhibitors have been reported and used for breast ...cancer therapy in recent years, especially in TNBC. However, developing a new type PARP inhibitor with distinctive skeleton is alternatively promising strategy for TNBC therapy. In this study, based on co-crystallization studies and pharmacophore-docking-based virtual screening, we discovered a series of dihydrodibenzob,e-oxepin compounds as PARP1 inhibitors. Lead optimization result in the identification of compound OL-1 (2-(11-(3-(dimethylamino)propylidene)-6,11- dihydrodibenzob,eoxepin )-2-yl)acetohydrazide), which has a novel chemical scaffold and unique binding interaction with PARP1 protein. OL-1 demonstrated excellent potency (inhibiting PARP1 enzyme activity with IC
= 0.079 μM), as well as inhibiting PARP-modulated PARylation and cell proliferation in MDA-MB-436 cells (BRAC1 mutation). In addition, OL-1 also inhibited cell migration that closely related to cancer metastasis and displayed remarkable anti-tumor efficacy in MDA-MB-436 xenograft model without apparent toxicities. These findings highlight a new small-molecule PAPR1 inhibitor (OL-1) that has the potential to impact future TNBC therapy.
Signet-ring cell carcinoma (SRCC) has specific epidemiology and oncogenesis in gastric cancer, however, with no systematical investigation for prognostic genomic features. Here we report a systematic ...investigation conducted in 1868 Chinese gastric cancer patients indicating that signet-ring cells content was related to multiple clinical characteristics and treatment outcomes. We thus perform whole-genome sequencing on 32 pairs of SRC samples, and identify frequent CLDN18-ARHGAP26/6 fusion (25%). With 797 additional patients for validation, prevalence of CLDN18-ARHGAP26/6 fusion is noticed to be associated with signet-ring cell content, age at diagnosis, female/male ratio, and TNM stage. Importantly, patients with CLDN18-ARHGAP26/6 fusion have worse survival outcomes, and get no benefit from oxaliplatin/fluoropyrimidines-based chemotherapy, which is consistent with the fact of chemo-drug resistance acquired in CLDN18-ARHGAP26 introduced cell lines. Overall, this study provides insights into the clinical and genomic features of SRCC, and highlights the importance of frequent CLDN18-ARHGAP26/6 fusions in chemotherapy response for SRCC.
Checkpoint inhibitor (CPI) based immunotherapy (i.e., anit-CTLA-4/PD-1/PD-L1 antibodies) can effectively prolong overall survival of patients across several cancer types at the advanced stage. ...However, only part of patients experience objective responses from such treatments, illustrating large individual differences in terms of both efficacy and adverse drug reactions. Through the observation on a series of CPI based clinical trials in independent patient cohorts, associations of multiple clinical and molecular characteristics with CPI response rate have been determined, including microenvironment, genomic alterations of the cancer cells, and even gut microbiota. A broad interest has been drawn to the question whether and how these prognostic factors can be used as biomarkers for optimal usage of CPIs in precision immunotherapy. Therefore, we reviewed the candidate prognostic factors identified by multiple trials and the experimental investigations, especially those reported in the recent 2 years, and described the possibilities and problems of them in routine clinical usage of cancer treatment as biomarkers.
AbstractObjectiveGuidelines from the Society for Vascular Surgery and the Choosing Wisely campaign recommend that peripheral vascular interventions (PVIs) be limited to claudication patients with ...lifestyle-limiting symptoms only after a failed trial of medical and exercise therapy. We sought to explore practice patterns and physician characteristics associated with early PVI after a new claudication diagnosis to evaluate adherence to these guidelines. MethodsWe used 100% Medicare fee-for-service claims to identify patients diagnosed with claudication for the first time between 2015 and 2017. Early PVI was defined as an aortoiliac or femoropopliteal PVI performed within 6 months of initial claudication diagnosis. A physician-level PVI utilization rate was calculated for physicians who diagnosed >10 claudication patients and performed at least one PVI (regardless of indication) during the study period. Hierarchical multivariable logistic regression was used to identify physician-level factors associated with early PVI. ResultsOf 194,974 patients who had a first-time diagnosis of claudication during the study period, 6286 (3.2%) underwent early PVI. Among the 5664 physicians included in the analysis, the median physician-level early PVI rate was low at 0% (range, 0%-58.3%). However, there were 320 physicians (5.6%) who had an early PVI rate ≥14% (≥2 standard deviations above the mean). After accounting for patient characteristics, a higher percentage of services delivered in ambulatory surgery center or office settings was associated with higher PVI utilization (vs 0%-22%; 23%-47%: adjusted odds ratio aOR, 1.23; 48%-68%: aOR, 1.49; 69%-100%: aOR, 1.72; all P < .05). Other risk-adjusted physician factors independently associated with high PVI utilization included male sex (aOR, 2.04), fewer years in practice (vs ≥31 years; 11-20 years: aOR, 1.23; 21-30 years: aOR, 1.13), rural location (aOR, 1.25), and lower volume claudication practice (vs ≥30 patients diagnosed during study period; ≤17 patients: aOR, 1.30; 18-29 patients: aOR, 1.35; all P < .05). ConclusionsOutlier physicians with a high early PVI rate for patients newly diagnosed with claudication are identifiable using a claims-based practice pattern measure. Given the shared Society for Vascular Surgery and Choosing Wisely initiative goal to avoid interventions for first-line treatment of claudication, confidential data-sharing programs using national benchmarks and educational guidance may be useful to address high utilization in the management of claudication.
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