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Dental caries, a common oral disease, poses serious risks if untreated, necessitating effective preventive measures like pit and fissure sealing. However, the reliance on experienced dentists for pit and fissures or caries detection limits accessibility, potentially leading to missed treatment opportunities, especially among children. To bridge this gap, we leverage deep learning in object detection to develop a method for autonomously identifying caries and determining pit and fissure sealing requirements using smartphone oral photos. We test several detection models and adopt a tiling strategy to reduce information loss during image pre‐processing. Our implementation achieves 72.3 mAP.5 with the YOLOXs model and tiling strategy. We enhance accessibility by deploying the pre‐trained network as a WeChat applet on mobile devices, enabling in‐home detection by parents or guardians. In addition, our data set of children's first permanent molars will also aid in the broader study of pediatric oral disease. [ABSTRACT FROM AUTHOR]

The outbreak of the monkeypox virus (MPXV) in non-endemic countries is an emerging global health threat and may have an economic impact if proactive actions are not taken. As shown by the COVID-19 pandemic, rapid, accurate, and cost-effective virus detection techniques play a pivotal role in disease diagnosis and control. Considering the sudden multicountry MPXV outbreak, a critical evaluation of the MPXV detection approaches would be a timely addition to the endeavors in progress for MPXV control and prevention. Herein, we evaluate the current MPXV detection methods, discuss their pros and cons, and provide recommended solutions to the problems. We review the traditional and emerging nucleic acid detection approaches, immunodiagnostics, whole-particle detection, and imaging-based MPXV detection techniques. The insights provided in this article will help researchers to develop novel techniques for the diagnosis of MPXV. [ABSTRACT FROM AUTHOR]

Despite the broad-spectrum antimicrobial activities of silver, its internal usage is restricted, owing to the toxicity. Strategies to enhance its efficacy are highly desirable but rely heavily on the understanding of its molecular mechanism of action. However, up to now, no direct silver-targeting proteins have been mined at a proteome-wide scale, which hinders systemic studies on the biological pathways interrupted by silver. Herein, we build up a unique system, namely liquid chromatography gel electrophoresis inductively coupled plasma mass spectrometry (LC-GE-ICP-MS), allowing 34 proteins directly bound by silver ions to be identified in Escherichia coli. By using integrated omic approaches, including metalloproteomics, metabolomics, bioinformatics, and systemic biology, we delineated the first dynamic antimicrobial actions of silver (Ag+) in E. coli, i.e., it primarily damages multiple enzymes in glycolysis and tricarboxylic acid (TCA) cycle, leading to the stalling of the oxidative branch of the TCA cycle and an adaptive metabolic divergence to the reductive glyoxylate pathway. It then further damages the adaptive glyoxylate pathway and suppresses the cellular oxidative stress responses, causing systemic damages and death of the bacterium. To harness these novel findings, we coadministrated metabolites involved in the Krebs cycles with Ag+ and found that they can significantly potentiate the efficacy of silver both in vitro and in an animal model. Our study reveals the comprehensive and dynamic mechanisms of Ag+ toxicity in E. coli cells and offers a novel and general approach for deciphering molecular mechanisms of metallodrugs in various pathogens and cells to facilitate the development of new therapeutics. [ABSTRACT FROM AUTHOR]

Urease as a potential target of antimicrobial drugs has received considerable attention given its versatile roles in microbial infection. Development of effective urease inhibitors, however, is a significant challenge due to the deeply buried active site and highly specific substrate of a bacterial urease. Conventionally, urease inhibitors are designed by either targeting the active site or mimicking substrate of urease, which is not efficient. Up to now, only one effective inhibitor—acetohydroxamic acid (AHA)—is clinically available, but it has adverse side effects. Herein, we demonstrate that a clinically used drug, colloid bismuth subcitrate, utilizes an unusual way to inhibit urease activity, i.e., disruption of urease maturation process via functional perturbation of a metallochaperone, UreG. Similar phenomena were also observed in various pathogenic bacteria, suggesting that UreG may serve as a general target for design of new types of urease inhibitors. Using Helicobacter pylori UreG as a showcase, by virtual screening combined with experimental validation, we show that two compounds targeting UreG also efficiently inhibited urease activity with inhibitory concentration (IC)50 values of micromolar level, resulting in attenuated virulence of the pathogen. We further demonstrate the efficacy of the compounds in a mammalian cell infection model. This study opens up a new opportunity for the design of more effective urease inhibitors and clearly indicates that metallochaperones involved in the maturation of important microbial metalloenzymes serve as new targets for devising a new type of antimicrobial drugs. [ABSTRACT FROM AUTHOR]

Uniform bismuth oxide (Bi2O3) and bismuth subcarbonate ((BiO)2CO3) nanotubes were successfully synthesized by a facile solvothermal method without the need for any surfactants or templates. The synergistic effect of ethylene glycol (EG) and urea played a critical role in the formation of the tubular nanostructures. These Bi2O3 and (BiO)2CO3 nanotubes exhibited excellent CrVI-removal capacity. Bi2O3 nanotubes, with a maximum CrVI-removal capacity of 79 mg g−1, possessed high removal ability in a wide range of pH values (3-11). Moreover, Bi2O3 and (BiO)2CO3 nanotubes also displayed highly efficient photocatalytic activity for the degradation of RhB under visible-light irradiation. This work not only demonstrates a new and facile route for the fabrication of Bi2O3 and (BiO)2CO3 nanotubes, but also provides new promising adsorbents for the removal of heavy-metal ions and potential photocatalysts for environmental remediation. [ABSTRACT FROM AUTHOR]

[Display omitted] • Intrinsic and TNFα-mediated extrinsic apoptosis are increased in early cystogenesis in PKD1+/− pig kidneys. • PKD1 deficiency in pig kidney does not affect pyroptosis and autophagy. • In vitro, PKD1 deficiency increases intrinsic apoptosis, but not extrinsic apoptosis. Apoptosis is a form of cell death that plays a critical role in the maintenance of tissue homeostasis involving the development and elimination of unwanted cells. Dysregulation of apoptosis appears to be associated in the pathogenesis of many human diseases. Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenetic disease and is mainly caused by mutations in PKD1. Previous studies proved that increased cell death occurred in ADPKD patients and animal models. However, the role of apoptosis in kidney cystogenesis is not clear. In current study, due to the high similarities between human and pig, PKD1 -deficient (PKD1+/−) pigs and PKD1 -knockdown (PKD1KD) pig kidney epithelial cells were used to investigate the mechanisms of apoptosis in driving cystogenesis. In PKD1+/− pigs, increased intrinsic and extrinsic apoptosis were found at ages of 1 month and 3 months, whereas the autophagy and pyroptosis were not altered. Meanwhile, the intrinsic apoptosis was activated along with untouched extrinsic apoptosis in PKD1KD pig kidney cells. Thus, the intrinsic apoptosis played important roles in cystogenesis. This work provides detail analysis of the roles of different cell death types during cystogenesis in ADPKD pig model. The results suggested a potential new strategy for the diagnosis and treatment of ADPKD by targeting intrinsic apoptosis. [ABSTRACT FROM AUTHOR]

Abstract: A facile solvothermal synthetic route has been successfully developed to fabricate Pd/Fe3O4 nanocomposite with the assistance of polyvinylpyrrolidone (PVP) in N,N-dimethylformamide (DMF) solution. The as-prepared Pd/Fe3O4 nanocomposite was composed of uniform 5nm-sized Pd nanoparticles and Fe3O4 nanocrystals with dimension of 40nm. In this fabrication, PVP played an important role as a capping agent. The as-prepared Pd/Fe3O4 nanocomposite exhibited superior catalytic performance and stability for various Suzuki coupling reactions, compared with single-component Pd nanoparticles under the same reaction conditions. More importantly, it displayed good magnetic property and could be easily separated from the reaction mixture by using a magnet and recycled for 10 times without losing its catalytic activity. [Copyright &y& Elsevier]

SARS-CoV-2 is a highly contagious pathogen that predominantly caused the COVID-19 pandemic. The persistent effects of COVID-19 are defined as an inflammatory or host response to the virus that begins four weeks after initial infection and persists for an undetermined length of time. Chronic effects are more harmful than acute ones thus, this review explored the long-term effects of the virus on various human organs, including the pulmonary, cardiovascular, and neurological, reproductive, gastrointestinal, musculoskeletal, endocrine, and lymphoid systems and found that SARS-CoV-2 adversely affects these organs of older adults. Regarding diagnosis, the RT-PCR is a gold standard method of diagnosing COVID-19; however, it requires specialized equipment and personnel for performing assays and a long time for results production. Therefore, to overcome these limitations, artificial intelligence employed in imaging and microfluidics technologies is the most promising in diagnosing COVID-19. Pharmacological and non-pharmacological strategies are the most effective treatment for reducing the persistent impacts of COVID-19 by providing immunity to post-COVID-19 patients by reducing cytokine release syndrome, improving the T cell response, and increasing the circulation of activated natural killer and CD8 T cells in blood and tissues, which ultimately reduces fever, nausea, fatigue, and muscle weakness and pain. Vaccines such as inactivated viral, live attenuated viral, protein subunit, viral vectored, mRNA, DNA, or nanoparticle vaccines significantly reduce the adverse long-term virus effects in post-COVID-19 patients; however, no vaccine was reported to provide lifetime protection against COVID-19; consequently, protective measures such as physical separation, mask use, and hand cleansing are promising strategies. This review provides a comprehensive knowledge of the persistent effects of COVID-19 on people of varying ages, as well as diagnosis, treatment, vaccination, and future preventative measures against the spread of SARS-CoV-2., Competing Interests: Declaration of competing interest We have no conflicts of interest associated with this publication. I confirmed that the manuscript has been read and approved for submission by all the named authors., (Copyright © 2024. Published by Elsevier Inc.)

Neurons coordinate their activity to produce an astonishing variety of motor behaviors. Our present understanding of motor control has grown rapidly thanks to new methods for recording and analyzing populations of many individual neurons over time. In contrast, current methods for recording the nervous system's actual motor output - the activation of muscle fibers by motor neurons - typically cannot detect the individual electrical events produced by muscle fibers during natural behaviors and scale poorly across species and muscle groups. Here we present a novel class of electrode devices ('Myomatrix arrays') that record muscle activity at unprecedented resolution across muscles and behaviors. High-density, flexible electrode arrays allow for stable recordings from the muscle fibers activated by a single motor neuron, called a 'motor unit,' during natural behaviors in many species, including mice, rats, primates, songbirds, frogs, and insects. This technology therefore allows the nervous system's motor output to be monitored in unprecedented detail during complex behaviors across species and muscle morphologies. We anticipate that this technology will allow rapid advances in understanding the neural control of behavior and identifying pathologies of the motor system., Competing Interests: BC, MZ, KT, JM, AJ, AP, MW, KN, LT, EA, LO, NO, RG, PA, JL, YW, MK, TO, RK, AM, SO, RW, HM, AM, CL, GK, JK, WO, KQ, PP, GG, AT, SC, TK, TS, BB, MZ, CT, SG, AP, MG, EA, NT, DO, BT, SL, MC, RC, JP, SS No competing interests declared, CP, MB Reviewing editor, eLife, (© 2023, Chung, Zia et al.)

The opportunistic pathogen Pseudomonas aeruginosa ( P. aeruginosa ) causes infections that are difficult to treat, which is due to the bacterial natural resistance to antibiotics. The bacterium is also able to form a biofilm that protects the bacterium from clearance by the human immune system and leads to chronic infection. Herein, we synthesized and characterized a novel gallium compound that interferes with both the iron metabolism and quorum sensing system of P. aeruginosa to achieve a significant bactericidal activity. The compound could substantially reduce the secretion of bacterial virulence factors as well as eliminate biofilm formation. Integrative omics analysis indicates that this compound can significantly disturb the gene transcription and metabolism of P. aeruginosa . The effectiveness of the gallium compound was further validated in mammalian cell and murine skin infection models. Our study offers a new strategy to design new gallium-based antimicrobials to combat P. aeruginosa infection., Competing Interests: There are no conflicts to declare., (This journal is © The Royal Society of Chemistry.)

The emergence of SARS-CoV-2 variants of concern compromises vaccine efficacy and emphasizes the need for further development of anti-SARS-CoV-2 therapeutics, in particular orally administered take-home therapies. Cocktail therapy has shown great promise in the treatment of viral infection. Herein, we reported the potent preclinical anti-SARS-CoV-2 efficacy of a cocktail therapy consisting of clinically used drugs, e.g. colloidal bismuth subcitrate (CBS) or bismuth subsalicylate (BSS), and N -acetyl-l-cysteine (NAC). Oral administration of the cocktail reduced viral loads in the lung and ameliorated virus-induced pneumonia in a hamster infection model. The mechanistic studies showed that NAC prevented the hydrolysis of bismuth drugs at gastric pH via the formation of the stable component [Bi(NAC) 3 ], and optimized the pharmacokinetics profile of CBS in vivo . Combination of bismuth drugs with NAC suppressed the replication of a panel of medically important coronaviruses including Middle East respiratory syndrome-related coronavirus (MERS-CoV), Human coronavirus 229E (HCoV-229E) and SARS-CoV-2 Alpha variant (B.1.1.7) with broad-spectrum inhibitory activities towards key viral cysteine enzymes/proteases including papain-like protease (PL pro ), main protease (M pro ), helicase (Hel) and angiotensin-converting enzyme 2 (ACE2). Importantly, our study offered a potential at-home treatment for combating SARS-CoV-2 and future coronavirus infections., Competing Interests: H. S., K.-Y. Y., S. Y., R. W., H. L., J. F.-W. C., T. C. and S. W. have a pending patent application related to this manuscript. J. F.-W. C. has received travel grants from Pfizer Corporation Hong Kong and Astellas Pharma Hong Kong Corporation Limited and was an invited speaker for Gilead Sciences Hong Kong Limited and Luminex Corporation. The other authors declare no competing interests., (This journal is © The Royal Society of Chemistry.)

Drug-resistant superbugs pose a huge threat to human health. Infections by Enterobacteriaceae producing metallo-β-lactamases (MBLs), e.g., New Delhi metallo-β-lactamase 1 (NDM-1) are very difficult to treat. Development of effective MBL inhibitors to revive the efficacy of existing antibiotics is highly desirable. However, such inhibitors are not clinically available till now. Here we show that an anti-Helicobacter pylori drug, colloidal bismuth subcitrate (CBS), and related Bi(III) compounds irreversibly inhibit different types of MBLs via the mechanism, with one Bi(III) displacing two Zn(II) ions as revealed by X-ray crystallography, leading to the release of Zn(II) cofactors. CBS restores meropenem (MER) efficacy against MBL-positive bacteria in vitro, and in mice infection model, importantly, also slows down the development of higher-level resistance in NDM-1-positive bacteria. This study demonstrates a high potential of Bi(III) compounds as the first broad-spectrum B1 MBL inhibitors to treat MBL-positive bacterial infection in conjunction with existing carbapenems.

Multifunctional Bi2O3 porous nanospheres (PNs) with tunable size have been successfully synthesized via a facile solvothermal method. The obtained Bi2O3 porous nanospheres demonstrate outstanding performance in visible-light-driven photocatalysis for Cr(VI) and organic dye removal, inactivation of Gram-negative and Gram-positive bacteria, as well as template-synthesis for fabrication of bismuth-related hollow nanostructures.

Uniform bismuth oxide (Bi(2)O(3)) and bismuth subcarbonate ((BiO)(2)CO(3)) nanotubes were successfully synthesized by a facile solvothermal method without the need for any surfactants or templates. The synergistic effect of ethylene glycol (EG) and urea played a critical role in the formation of the tubular nanostructures. These Bi(2)O(3) and (BiO)(2)CO(3) nanotubes exhibited excellent Cr(VI)-removal capacity. Bi(2)O(3) nanotubes, with a maximum Cr(VI)-removal capacity of 79 mg g(-1), possessed high removal ability in a wide range of pH values (3-11). Moreover, Bi(2)O(3) and (BiO)(2)CO(3) nanotubes also displayed highly efficient photocatalytic activity for the degradation of RhB under visible-light irradiation. This work not only demonstrates a new and facile route for the fabrication of Bi(2)O(3) and (BiO)(2)CO(3) nanotubes, but also provides new promising adsorbents for the removal of heavy-metal ions and potential photocatalysts for environmental remediation., (Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)