Physical Devices (United States)

Gonorrhea, caused by N. gonorrhoeae , is a widespread sexually transmitted disease that is becoming resistant to all currently used antibiotics. Therefore, new therapeutics against gonorrhea are desperately needed. Here, we show that a natural product - aerocavin, is highly potent and specific against Neisseria . Aerocavin accumulates in N. gonorrhoeae at high levels and inhibits bacterial RNA polymerase (RNAP) by binding the switch region. Aerocavin resistance mutations evolve in N. gonorrhoeae at a low rate and are absent in clinical isolates. Previously overlooked narrow-spectrum antimicrobials like aerocavin may enable microbiome-sparing treatments of gonorrhea.

Mass spectrometry (MS)-based top–down proteomics (TDP) has emerged as a powerful tool for characterizing proteoforms to advance both fundamental and translational research. TDP requires high-efficiency liquid-phase separation, high-resolution MS, and tandem MS. Capillary zone electrophoresis (CZE)-MS has been proposed as a promising analytical technique for protein analysis decades ago because of its unique and valuable features, including high separation efficiency and high detection sensitivity. However, CZE-MS has not been widely adopted by the proteomics community, mainly due to concerns with its robustness and reproducibility. Here, we hypothesized that CZE-MS is sufficiently robust and reproducible for broad adoption due to the continued efforts of the community over the last three decades. In this work, for the first time, research teams from around the world validated the robustness, repeatability, and reproducibility of CZE-MS for TDP in both simple and complex model proteoform mixtures employing a full spectrum of commercially available capillary electrophoresis (CE)-MS interfaces, instrumentation, and compared CZE-MS performance with state-of-the-art liquid chromatography (LC)-MS methods. This study offers the research community an informative resource of ready-to-use experimental CE-MS techniques and a better understanding of the CZE-MS approach and its potential in TDP, accelerating the broad adoption of CZE-MS in proteoform research.

Department of Psychiatry, Southern Illinois University School of Medicine, Springfield, IL. Received for publication May 12, 2023; accepted May 15, 2023. Reprints: Conrad M. Swartz, PhD, MD, 12911 NW 25th Ct, Vancouver, WA 98685-2036 (e-mail: [email protected]). The author is an officer of Somatics LLC, a manufacturer of electroconvulsive therapy devices and supplies.

Self-supervised learning (SSL) for speech is effective for various downstream tasks. However, the strategies for selecting upstream models, layer depths where intermediate representations are passed from upstream to downstream, and downstream model structures should be clarified. In this study, SSL was applied to speech emotion recognition (SER), where paralinguistic information is relevant. We investigated the wav2vec 2.0, HuBERT, and WavLM models on two SER datasets: IEMOCAP and RAVDESS. Moreover, we compared different layer depths in the upstream model and examined mean and attention pooling in the downstream model. Our experimental results revealed the following: predictive models are preferred over contrastive models for paralinguistic tasks; paralinguistic information is incorporated in the middle layers; the information relevant to SER is not extremely localized in time; and a single layer includes sufficiently effective information compared with the weighted sum. Our best model outperformed previous models in the frozen upstream condition.

During autoimmunity or organ transplant rejection, the immune system attacks host or transplanted tissue, causing debilitating inflammation for millions of patients. There is no cure for most of these diseases. Further, available therapies modulate inflammation through nonspecific pathways, reducing symptoms but also compromising patients' ability to mount healthy immune responses. Recent preclinical advances to regulate immune dysfunction with vaccine-like antigen specificity reveal exciting opportunities to address the root cause of autoimmune diseases and transplant rejection. Several of these therapies are currently undergoing clinical trials, underscoring the promise of antigen-specific tolerance. Achieving antigen-specific tolerance requires precision and often combinatorial delivery of antigen, cytokines, small molecule drugs, and other immunomodulators. This can be facilitated by biomaterial technologies, which can be engineered to orient and display immunological cues, protect against degradation, and selectively deliver signals to specific tissues or cell populations. In this review, some key immune cell populations involved in autoimmunity and healthy immune tolerance are described. Opportunities for drug delivery to immunological organs are discussed, where specialized tissue-resident immune cells can be programmed to respond in unique ways toward antigens. Finally, cell- and biomaterial-based therapies to induce antigen-specific immune tolerance that are currently undergoing clinical trials are highlighted.

Over the past 20 years, innovations in microsurgical technique have coincided with advances in orthoplastic approaches. However, no single algorithm exists to guide management of limb salvage versus amputation. As such, one would expect these procedures to be performed at equal rates given studies showing similar outcomes. Anecdotally, the observation at the authors' institution is that amputations are being performed more frequently. The purpose of this study was to determine trends in lower extremity trauma management. A retrospective cohort study was conducted at a Level I trauma center on patients with Gustilo type IIIB/IIIC lower extremity trauma from 2005 to 2014. Overall, 148 patients were included. Patients were subdivided into amputation (n = 69) and reconstruction (n = 79) cohorts. The Spearman rank correlation coefficient was used to compare trends in amputation and reconstruction groups. Plastic surgery consultation data were analyzed using the Mann-Whitney U and chi-square tests and the Pearson correlation coefficient. Amputation was performed more frequently over the study period (r = 0.292; p < 0.001). Plastic surgeons were consulted in 67.5 percent of cases. A plastic surgery consultation was obtained in only 30 percent of amputation cases (p < 0.001). Although the data show a trend toward amputation and a shift in management of lower extremity trauma, the observed trend may be attributable in part to deviation from an orthoplastic approach to lower extremity trauma. However, lower extremity reconstruction remains a viable option in select patients, and advances in microsurgery can provide excellent outcomes in the face of severe lower extremity trauma.

Direct growth of self-supported one-dimensional (1D) nanorod arrays on conducting substrates is highly attractive for electrocatalysis, due to their unique shape, size, and length. In this work, a facile and simple two-step method was employed to synthesize 1D-CoSe2 nanoarrays on titanium (Ti) foil via a wet chemical ion-exchange approach. The as-synthesized 1D-CoSe2 nanoarrays were directly used as electrode materials for hydrogen evolution reaction and supercapacitors. As an electrocatalyst, the optimized 1D-CoSe2(tex-48 h) nanoarray exhibits excellent hydrogen evolution properties with a small Tafel slope of 78 mV dec-1, low overpotentials of 41 mV@1 mA cm-2 and 216 mV@10 mA cm-2, and extended robust performance for 25 h. Moreover, for a symmetric device, it delivers a maximum specific capacitance of 152 F g-1 at 0.5 A g-1 and a better energy density of 21.1 W h kg-1 at a power density of 0.5 kW kg-1. Also, the symmetric device capacity retention behavior achieves ∼96.8% of the initial result after 5000 cycles, revealing the good stability of the electrode. Our findings offer a new way to further the development of high-performance energy devices.

A new lead-free 0.76BNT-0.24NN relaxor AFE ceramic exhibits linear P–E, S–P2 and S–E2 responses and giant purely-electrostrictive strains of ∼0.20% within ˂10% in a wide temperature range owing to the existence of anti-polar nanoregions (APNRs).