Mechanistic insights into the C-type lectin receptor CLEC12A-mediated immune recognition of monosodium urate crystal.

CLEC12A, a member of the C-type lectin receptor family involved in immune homeostasis, recognizes MSU crystals released from dying cells. However, the molecular mechanism underlying the CLEC12A-mediated recognition of MSU crystals remains unclear. Herein, we reported the crystal structure of the human CLEC12A-C-type lectin-like domain (CTLD) and identified a unique "basic patch" site on CLEC12A-CTLD that is necessary for the binding of MSU crystals. Meanwhile, we determined the interaction strength between CLEC12A-CTLD and MSU crystals using single-molecule force spectroscopy. Furthermore, we found that CLEC12A clusters at the cell membrane and seems to serve as an internalizing receptor of MSU crystals. Altogether, these findings provide mechanistic insights for understanding the molecular mechanisms underlying the interplay between CLEC12A and MSU crystals.

Click Chemistry-Based Force Spectroscopy Revealed Enhanced Binding Dynamics of Phosphorylated HMGB1 to Cisplatin-DNA.

Cisplatin, a cornerstone in cancer chemotherapy, is known for its DNA-binding capacity and forms lesions that lead to cancer cell death. However, the repair of these lesions compromises cisplatin's effectiveness. This study investigates how phosphorylation of HMGB1, a nuclear protein, modifies its binding to cisplatin-modified DNA (CP-DNA) and thus protects it from repair. Despite numerous methods for detecting protein-DNA interactions, quantitative approaches for understanding their molecular mechanism remain limited. Here, we applied click chemistry-based single-molecule force spectroscopy, achieving high-precision quantification of the interaction between phosphorylated HMGB1 and CP-DNA. This method utilizes a synergy of click chemistry and enzymatic ligation for precise DNA-protein immobilization and interaction in the system. Our results revealed that HMGB1 binds to CP-DNA with a significantly high rupture force of ∼130 pN, stronger than most natural DNA-protein interactions and varying across different DNA sequences. Moreover, Ser14 is identified as the key phosphorylation site, enhancing the interaction's kinetic stability by 35-fold. This increase in stability is attributed to additional hydrogen bonding suggested by molecular dynamics (MD) simulations. Our findings not only reveal the important role of phosphorylated HMGB1 in potentially improving cisplatin's therapeutic efficacy but also provide a precise method for quantifying protein-DNA interactions.

Intratumor APOL3 delineates a distinctive immunogenic ferroptosis subset with prognosis prediction in colorectal cancer.

With the essential role of lipid transporting signaling in cancer-related immunity, apolipoprotein L3 (APOL3), a member of the apolipoprotein L gene family, demonstrated significant modulation ability in immunity. However, the expression profile and critical role of APOL3 in colorectal cancer (CRC) remain unclear. This study aimed to investigate the prognostic significance of APOL3 expression and its biological predictive value in CRC. The study enrolled multiple cohorts, consisting of 911 tumor microarray specimens of CRC patients from Zhongshan Hospital, 412 transcriptional data from The Cancer Genome Atlas, and 30 single-cell RNA sequencing (scRNA-seq) from internal and external CRC patients. APOL3 mRNA expression was directly acquired from public datasets, and APOL3 protein expression was detected using immunohistochemistry. Finally, the associations of APOL3 expression with clinical outcomes, immune context, and genomic and ferroptotic features were analyzed. Low APOL3 expression predicted poor prognosis and inferior responsiveness to 5-fluorouracil-based adjuvant chemotherapy (ACT) and targeted therapy. APOL3 fosters an immune-active microenvironment characterized by the promotion of ferroptosis, downregulation of macrophages, and upregulation of CD8+ T cell infiltration. Moreover, the expression of APOL3 in CD8+ T cells is intrinsically linked to ferroptosis and immune activation in CRC. In summary, APOL3 serves as an independent prognosticator and predictive biomarker for immunogenic ferroptosis, ACT, and targeted therapy in CRC. Furthermore, the APOL3 signaling activator could be a novel agent alone or in combination with current therapeutic strategies for CRC.

Molecular force-induced liberation of transforming growth factor-beta remodels the spleen for ectopic liver regeneration.

BACKGROUND & AIMS: Ectopic liver regeneration in the spleen is a promising alternative to organ transplantation for treating liver failure. To accommodate transplanted liver cells, the splenic tissue must undergo structural changes to increase extracellular matrix content, demanding a safe and efficient approach for tissue remodelling. METHODS: We synthesised sulphated hyaluronic acid (sHA) with an affinity for the latent complex of transforming growth factor-ß (TGF-ß) and cross-linked it into a gel network (sHA-X) via click chemistry. We injected this glycan into the spleens of mice to induce splenic tissue remodelling via supraphysiological activation of endogenous TGF-ß. RESULTS: sHA-X efficiently bound to the abundant latent TGF-ß in the spleen. It provided the molecular force to liberate the active TGF-ß dimers from their latent complex, mimicking the 'bind-and-pull' mechanism required for physiological activation of TGF-ß and reshaping the splenic tissue to support liver cell growth. Hepatocytes transplanted into the remodelled spleen developed into liver tissue with sufficient volume to rescue animals with a metabolic liver disorder (Fah-/- transgenic model) or following 90% hepatectomy, with no adverse effects observed and no additional drugs required. CONCLUSION: Our findings highlight the efficacy and translational potential of using sHA-X to remodel a specific organ by mechanically activating one single cytokine, representing a novel strategy for the design of biomaterials-based therapies for organ regeneration. IMPACT AND IMPLICATIONS: Cell transplantation may provide a lifeline to millions of patients with end-stage liver diseases, but their severely damaged livers being unable to accommodate the transplanted cells is a crucial hurdle. Herein, we report an approach to restore liver functions in another organ - the spleen - by activating one single growth factor in situ. This approach, based on a chemically designed polysaccharide that can mechanically liberate the active transforming growth factor-ß to an unusually high level, promotes the function of abundant allogenic liver cells in the spleen, rescuing animals from lethal models of liver diseases and showing a high potential for clinical translation.

Assessing COVID-19 pandemic policies and behaviours and their economic and educational trade-offs across US states from Jan 1, 2020, to July 31, 2022: an observational analysis.

BACKGROUND: The USA struggled in responding to the COVID-19 pandemic, but not all states struggled equally. Identifying the factors associated with cross-state variation in infection and mortality rates could help to improve responses to this and future pandemics. We sought to answer five key policy-relevant questions regarding the following: 1) what roles social, economic, and racial inequities had in interstate variation in COVID-19 outcomes; 2) whether states with greater health-care and public health capacity had better outcomes; 3) how politics influenced the results; 4) whether states that imposed more policy mandates and sustained them longer had better outcomes; and 5) whether there were trade-offs between a state having fewer cumulative SARS-CoV-2 infections and total COVID-19 deaths and its economic and educational outcomes. METHODS: Data disaggregated by US state were extracted from public databases, including COVID-19 infection and mortality estimates from the Institute for Health Metrics and Evaluation's (IHME) COVID-19 database; Bureau of Economic Analysis data on state gross domestic product (GDP); Federal Reserve economic data on employment rates; National Center for Education Statistics data on student standardised test scores; and US Census Bureau data on race and ethnicity by state. We standardised infection rates for population density and death rates for age and the prevalence of major comorbidities to facilitate comparison of states' successes in mitigating the effects of COVID-19. We regressed these health outcomes on prepandemic state characteristics (such as educational attainment and health spending per capita), policies adopted by states during the pandemic (such as mask mandates and business closures), and population-level behavioural responses (such as vaccine coverage and mobility). We explored potential mechanisms connecting state-level factors to individual-level behaviours using linear regression. We quantified reductions in state GDP, employment, and student test scores during the pandemic to identify policy and behavioural responses associated with these outcomes and to assess trade-offs between these outcomes and COVID-19 outcomes. Significance was defined as p<0·05. FINDINGS: Standardised cumulative COVID-19 death rates for the period from Jan 1, 2020, to July 31, 2022 varied across the USA (national rate 372 deaths per 100 000 population [95% uncertainty interval [UI] 364-379]), with the lowest standardised rates in Hawaii (147 deaths per 100 000 [127-196]) and New Hampshire (215 per 100 000 [183-271]) and the highest in Arizona (581 per 100 000 [509-672]) and Washington, DC (526 per 100 000 [425-631]). A lower poverty rate, higher mean number of years of education, and a greater proportion of people expressing interpersonal trust were statistically associated with lower infection and death rates, and states where larger percentages of the population identify as Black (non-Hispanic) or Hispanic were associated with higher cumulative death rates. Access to quality health care (measured by the IHME's Healthcare Access and Quality Index) was associated with fewer total COVID-19 deaths and SARS-CoV-2 infections, but higher public health spending and more public health personnel per capita were not, at the state level. The political affiliation of the state governor was not associated with lower SARS-CoV-2 infection or COVID-19 death rates, but worse COVID-19 outcomes were associated with the proportion of a state's voters who voted for the 2020 Republican presidential candidate. State governments' uses of protective mandates were associated with lower infection rates, as were mask use, lower mobility, and higher vaccination rate, while vaccination rates were associated with lower death rates. State GDP and student reading test scores were not associated with state COVD-19 policy responses, infection rates, or death rates. Employment, however, had a statistically significant relationship with restaurant closures and greater infections and deaths: on average, 1574 (95% UI 884-7107) additional infections per 10 000 population were associated in states with a one percentage point increase in employment rate. Several policy mandates and protective behaviours were associated with lower fourth-grade mathematics test scores, but our study results did not find a link to state-level estimates of school closures. INTERPRETATION: COVID-19 magnified the polarisation and persistent social, economic, and racial inequities that already existed across US society, but the next pandemic threat need not do the same. US states that mitigated those structural inequalities, deployed science-based interventions such as vaccination and targeted vaccine mandates, and promoted their adoption across society were able to match the best-performing nations in minimising COVID-19 death rates. These findings could contribute to the design and targeting of clinical and policy interventions to facilitate better health outcomes in future crises. FUNDING: Bill & Melinda Gates Foundation, J Stanton, T Gillespie, J and E Nordstrom, and Bloomberg Philanthropies.

Fast Nano-IR Hyperspectral Imaging Empowered by Large-Dataset-Free Miniaturized Spatial-Spectral Network.

The emerging field of nanoscale infrared (nano-IR) offers label-free molecular contrast, yet its imaging speed is limited by point-by-point traverse acquisition of a three-dimensional (3D) data cube. Here, we develop a spatial-spectral network (SS-Net), a miniaturized deep-learning model, together with compressive sampling to accelerate the nano-IR imaging. The compressive sampling is performed in both the spatial and spectral domains to accelerate the imaging process. The SS-Net is trained to learn the mapping from small nano-IR image patches to the corresponding spectra. With this elaborated mapping strategy, the training can be finished quickly within several minutes using the subsampled data, eliminating the need for a large-labeled dataset of common deep learning methods. We also designed an efficient loss function, which incorporates the image and spectral similarity to enhance the training. We first validate the SS-Net on an open stimulated Raman-scattering dataset; the results exhibit the potential of 10-fold imaging speed improvement with state-of-the-art performance. We then demonstrate the versatility of this approach on atomic force microscopy infrared (AFM-IR) microscopy with 7-fold imaging speed improvement, even on nanoscale Fourier transform infrared (nano-FTIR) microscopy with up to 261.6 folds faster imaging speed. We further showcase the generalization of this method on AFM-force volume-based multiparametric nanoimaging. This method establishes a paradigm for rapid nano-IR imaging, opening new possibilities for cutting-edge research in materials, photonics, and beyond.

Polymorphic Heterogeneous Polar Structure Enabled Superior Capacitive Energy Storage in Lead-Free Relaxor Ferroelectrics at Low Electric Field.

High-performance energy storage dielectrics capable of low/moderate field operation are vital in advanced electrical and electronic systems. However, in contrast to achievements in enhancing recoverable energy density (Wrec), the active realization of superior Wrec and energy efficiency (η) with giant energy-storage coefficient (Wrec/E) in low/moderate electric field (E) regions is much more challenging for dielectric materials. Herein, lead-free relaxor ferroelectrics are reported with giant Wrec/E designed with polymorphic heterogeneous polar structure. Following the guidance of Landau phenomenological theory and rational composition construction, the conceived (Bi0.5Na0.5)TiO3-based ternary solid solution that delivers giant Wrec/E of ≈0.0168 µC cm-2, high Wrec of ≈4.71 J cm-3 and high η of ≈93% under low E of 280 kV cm-1, accompanied by great stabilities against temperature/frequency/cycling number and excellent charging-discharging properties, which is ahead of most currently reported lead-free energy storage bulk ceramics measured at same E range. Atomistic observations reveal that the correlated coexisting local rhombohedral-tetragonal polar nanoregions embedded in the cubic matrix are constructed, which enables high polarization, minimized hysteresis, and significantly delayed polarization saturation concurrently, endowing giant Wrec/E along with high Wrec and η. These findings advance the superiority and feasibility of polymorphic nanodomains in designing highly efficient capacitors for low/moderate field-region practical applications.

Quantitative Detection of Thyroid-Stimulating Hormone in Patient Samples with a Nanomechanical Single-Antibody Spectro-Immunoassay.

Functional disorders of the thyroid remain a global challenge and have profound impacts on human health. Serving as the barometer for thyroid function, thyroid-stimulating hormone (TSH) is considered the single most useful test of thyroid function. However, the prevailing TSH immunoassays rely on two types of antibodies in a sandwich format. The requirement of repeated incubation and washing further complicates the issue, making it unable to meet the requirements of the shifting public health landscape that demands rapid, sensitive, and low-cost TSH tests. Herein, a systematic study is performed to investigate the clinical translational potential of a single antibody-based biosensing platform for the TSH test. The biosensing platform leverages Raman spectral variations induced by the interaction between a TSH antigen and a Raman molecule-conjugated TSH antibody. In conjunction with machine learning, it allows TSH concentrations in various patient samples to be predicted with high accuracy and precision, which is robust against substrate-to-substrate, intra-substrate, and day-to-day variations. It is envisioned that the simplicity and generalizability of this single-antibody immunoassay coupled with the demonstrated performance in patient samples pave the way for it to be widely applied in clinical settings for low-cost detection of hormones, other molecular biomarkers, DNA, RNA, and pathogens.

Single-Atom Ru Alloyed with Ni Nanoparticles Boosts CO2 Methanation.

Designing catalysts to proceed with catalytic reactions along the desired reaction pathways, e.g., CO2 methanation, has received much attention but remains a huge challenge. This work reports one Ru1Ni single-atom alloy (SAA) catalyst (Ru1Ni/SiO2) prepared via a galvanic replacement reaction between RuCl3 and Ni nanoparticles (NPs) derived from the reduction of Ni phyllosilicate (Ni-ph). Ru1Ni/SiO2 achieved much improved selectivity toward hydrogenation of CO2 to CH4 and catalytic activity (Turnover frequency (TOF) value: 40.00 × 10-3 s-1), much higher than those of Ni/SiO2 (TOF value: 4.40 × 10-3 s-1) and most reported Ni-based catalysts (TOF value: 1.03 × 10-3-11.00 × 10-3 s-1). Experimental studies verify that Ru single atoms are anchored onto the Ni NPs surface via the Ru1-Ni coordination accompanied by electron transfer from Ru1 to Ni. Both in situ experiments and theoretical calculations confirm that the interface sites of Ru1Ni-SAA are the intrinsic active sites, which promote the direct dissociation of CO2 and lower the energy barrier for the hydrogenation of CO* intermediate, thereby directing and enhancing the CO2 hydrogenation to CH4.

Long non-coding RNA RP11-197K6.1 as ceRNA promotes colorectal cancer progression via miR-135a-5p/DLX5 axis.

BACKGROUND: Colorectal cancer (CRC) remains a major global health challenge, with high incidence and mortality rates. The role of long noncoding RNAs (lncRNAs) in cancer progression has received considerable attention. The present study aimed to investigate the function and mechanisms underlying the role of lncRNA RP11-197K6.1, microRNA-135a-5p (hsa-miR-135a-5p), and DLX5 in CRC development. METHODS: We analyzed RNA sequencing data from The Cancer Genome Atlas Colorectal Cancer dataset to identify the association between lncRNA RP11-197K6.1 and CRC progression. The expression levels of lncRNA RP11-197K6.1 and DLX5 in CRC samples and cell lines were determined by real-time quantitative PCR and western blotting assays. Fluorescence in situ hybridization was used to confirm the cellular localization of lncRNA RP11-197K6.1. Cell migration capabilities were assessed by Transwell and wound healing assays, and flow cytometry was performed to analyze apoptosis. The interaction between lncRNA RP11-197K6.1 and miR-135a-5p and its effect on DLX5 expression were investigated by the dual-luciferase reporter assay. Additionally, a xenograft mouse model was used to study the in vivo effects of lncRNA RP11-197K6.1 on tumor growth, and an immunohistochemical assay was performed to assess DLX5 expression in tumor tissues. RESULTS: lncRNA RP11-197K6.1 was significantly upregulated in CRC tissues and cell lines as compared to that in normal tissues, and its expression was inversely correlated with patient survival. It promoted the migration and metastasis of CRC cells by interacting with miR-135a-5p, alleviated suppression of DLX5 expression, and facilitated tumor growth. CONCLUSION: This study demonstrated the regulatory network and mechanism of action of the lncRNA RP11-197K6.1/miR-135a-5p/DLX5 axis in CRC development. These findings provided insights into the molecular pathology of CRC and suggested potential therapeutic targets for more effective treatment of patients with CRC.

The gut microbiome modulates the transformation of microglial subtypes.

Clinical and animal studies have shown that gut microbiome disturbances can affect neural function and behaviors via the microbiota-gut-brain axis, and may be implicated in the pathogenesis of several brain diseases. However, exactly how the gut microbiome modulates nervous system activity remains obscure. Here, using a single-cell nucleus sequencing approach, we sought to characterize the cell type-specific transcriptomic changes in the prefrontal cortex and hippocampus derived from germ-free (GF), specific pathogen free, and colonized-GF mice. We found that the absence of gut microbiota resulted in cell-specific transcriptomic changes. Furthermore, microglia transcriptomes were preferentially influenced, which could be effectively reversed by microbial colonization. Significantly, the gut microbiome modulated the mutual transformation of microglial subpopulations in the two regions. Cross-species analysis showed that the transcriptome changes of these microglial subpopulations were mainly associated with Alzheimer's disease (AD) and major depressive disorder (MDD), which were further supported by animal behavioral tests. Our findings demonstrate that gut microbiota mainly modulate the mutual transformation of microglial subtypes, which may lead to new insights into the pathogenesis of AD and MDD.

Association Between Early Sexual Debut and New HIV Infections Among Adolescents and Young Adults in 11 African Countries.

We investigated the association between early sexual debut and HIV infection among adolescents and young adults. Analyzing data from nationally representative Population-Based HIV Impact Assessment (PHIA) surveys in 11 African countries, the research employed a multivariate logistic regression model to assess the relationship between the early sexual debut and new HIV infections in the age group of 10-24 years. The results revealed a significant and robust association, indicating that young individuals who experienced early sexual debut were approximately 2.65 times more likely to contract HIV than those who did not, even after accounting for other variables. These findings align with prior research suggesting that early initiation of sexual activity may increase vulnerability to HIV infection due to factors such as biological susceptibility and risky behaviors like low condom use and multiple sexual partners. The implications of these findings for HIV prevention strategies are substantial, suggesting that interventions aimed at delaying sexual debut could be an effective component in reducing HIV risk for this population. Targeted sex education programs that address the risks of early sexual debut may play a pivotal role in these prevention efforts. By employing a comprehensive approach, there is a possibility to advance efforts towards ending AIDS by 2030.

Mechanism Involved in Polyvinyl Chloride Nanoplastics Induced Anaerobic Granular Sludge Disintegration: Microbial Interaction Energy, EPS Molecular Structure, and Metabolism Functions.

Nanoplastics (NPs) are emerging pollutants and have been reported to cause the disintegration of anaerobic granular sludge (AnGS). However, the mechanism involved in AnGS disintegration was not clear. In this study, polyvinyl chloride nanoplastics (PVC-NPs) were chosen as target NPs and their long-term impact on AnGS structure was investigated. Results showed that increasing PVC-NPs concentration resulted in the inhibition of acetoclastic methanogens, syntrophic propionate, and butyrate degradation, as well as AnGS disintegration. At the presence of 50 µg·L-1 PVC-NPs, the hydrophobic interaction was weakened with a higher energy barrier due to the relatively higher hydrophilic functional groups in extracellular polymeric substances (EPS). PVC-NPs-induced ROS inhibited quorum sensing, significantly downregulated hydrophobic amino acid synthesis, whereas it highly upregulated the genes related to the synthesis of four hydrophilic amino acids (Cys, Glu, Gly, and Lys), resulting in a higher hydrophily degree of protein secondary structure in EPS. The differential expression of genes involved in EPS biosynthesis and the resulting protein secondary structure contributed to the greater hydrophilic interaction, reducing microbial aggregation ability. The findings provided new insight into the long-term impact of PVC-NPs on AnGS when treating wastewater containing NPs and filled the knowledge gap on the mechanism involved in AnGS disintegration by PVC-NPs.

Machine learning in risk prediction of continuous renal replacement therapy after coronary artery bypass grafting surgery in patients.

OBJECTIVES: This study aimed to develop machine learning models for risk prediction of continuous renal replacement therapy (CRRT) following coronary artery bypass grafting (CABG) surgery in intensive care unit (ICU) patients. METHODS: We extracted CABG patients from the electronic medical record system of the hospital. The endpoint of this study was the requirement for CRRT after CABG surgery. The Boruta method was used for feature selection. Seven machine learning algorithms were developed to train models and validated using 10 fold cross-validation (CV). Model discrimination and calibration were estimated using the area under the receiver operating characteristic curve (AUC) and calibration plot, respectively. We used the SHapley Additive exPlanations (SHAP) method to illustrate the effects of the features attributed to the model and analyze the effects of individual features on the output of the mode. RESULTS: In this study, 72 (37.89%) patients underwent CRRT, with a higher mortality compared to those patients without CRRT. The Gaussian Naïve Bayes (GNB) model with the highest AUC were considered as the final predictive model and performed best in predicting postoperative CRRT. The analysis of importance revealed that cardiac troponin T, creatine kinase isoenzyme, albumin, low-density lipoprotein cholesterol, NYHA, serum creatinine, and age were the top seven features of the GNB model. The SHAP force analysis illustrated how created model visualized individualized prediction of CRRT. CONCLUSIONS: Machine learning models were developed to predict CRRT. This contributes to the identification of risk variables for CRRT following CABG surgery in ICU patients and enables the optimization of perioperative managements for patients.

Effects of radial extracorporeal shock wave therapy on flexor spasticity of the upper limb in post-stroke patients: A randomized controlled trial.

OBJECTIVE: This study aimed to assess the efficacy of radial extracorporeal shock wave therapy in treating upper limb spasticity after a stroke. DESIGN: Randomized controlled trial. SETTING: Zhujiang Hospital of Southern Medical University. SUBJECTS: This study included 95 people with stroke. INTERVENTION: The active (n = 47) and sham-placebo (n = 48) radial extracorporeal shockwave therapy groups received three treatment sessions (every third day). MAIN MEASURES: The Modified Ashworth Scale, Hmax/Mmax ratio, root mean square, co-contraction ratio, mechanical parameters of the muscle and temperature were measured at baseline and days 2, 5 and 8. RESULTS: Among the 135 potential participants screened, 100 were enrolled and allocated randomly, with 95 participants ultimately being included in the intent-to-treat analysis dataset. The active group showed significantly better improvements in upper limb spasticity and muscle function than did the sham-placebo group. Greater improvements in the Modified Ashworth Scale were observed in the active group than in the sham-placebo group (difference, -0.45; 95% CI, -0.69 to -0.22; P < 0.001). Moreover, significant differences in root mean square, co-contraction ratio and Hmax/Mmax ratio were observed between the two groups (all P < 0.001). The mechanical parameters of the biceps muscle were significantly better in the active group than in the sham-placebo group (P < 0.001). The active group had a higher temperature than the sham-placebo group, although the difference was not significant (P = 0.070). CONCLUSIONS: This study revealed that the treatment with extracorporeal shockwave therapy can relieve upper limb spasticity in people with stroke.

Deletion of ArmPT, a LamB-like protein, increases cell membrane permeability and antibiotic sensitivity in Vibrio alginolyticus.

Vibrio bacterial species are dominant pathogens in mariculture animals. However, the extensive use of antibiotics and other chemicals has increased drug resistance in Vibrio bacteria. Despite rigorous investigative studies, the mechanism of drug resistance in Vibrio remains a mystery. In this study, we found that a gene encoding LamB-like outer membrane protein, named ArmPT, was upregulated in Va under antibiotic stress by RT-qPCR. We speculated that ArmPT might play a role in Va's drug resistance. Subsequently, using ArmPT gene knockout and gene complementation experiments, we confirmed its role in resistance against a variety of antibiotics, particularly kanamycin (KA). Transcriptomic and proteomic analyses identified 188 and 83 differentially expressed genes in the mutant strain compared with the wild-type (WT) before and after KA stress, respectively. Bioinformatic analysis predicted that ArmPT might control cell membrane permeability by changing cadaverine biosynthesis, thereby influencing the cell entry of antibiotics in Va. The higher levels of intracellular reactive oxygen species and the infused content of KA showed that antibiotics are more likely to enter the Va mutant strain. These results uncover the drug resistance mechanism of Va that can also exist in other similar pathogenic bacteria.

Suture Tape Augmentation Improves Posterior Stability After Isolated Posterior Cruciate Ligament Reconstruction Using Hamstring Tendon Autograft With Single-Bundle Transtibial Technique.

PURPOSE: To assess whether posterior cruciate ligament reconstruction (PCLR) with suture tape augmentation can yield more stability after isolated PCLR. METHODS: A prospective database was retrospectively reviewed to identify patients who underwent primary isolated PCLR (control group) or isolated PCLR with suture tape augmentation (study group) from January 2016 to September 2020. We analyzed subjective International Knee Documentation Committee (IKDC), Lysholm, and Tegner knee scores; posterior drawer test findings; posterior stress radiographs; and return-to-sports activity rates. The minimal clinically important difference (MCID) was used to evaluate clinical relevance (subjective IKDC, Lysholm, and Tegner scores). RESULTS: A total of 59 patients were included in this analysis (28 in control group and 31 in study group). The average length of follow-up was similar between the study and control groups (48.6 months vs 47.9 months, P = .800). Knee function was significantly improved in the study group in terms of subjective IKDC scores (85.1 ± 6.4 in study group vs 79.8 ± 6.4 in control group, P = .002), Lysholm scores (86.3 ± 7.4 vs 80.8 ± 7.4, P = .005), and Tegner scores (7.0 ± 1.4 vs 5.6 ± 1.7, P = .006). However, the differences between the control and study groups were less than the MCID for the subjective IKDC score and Lysholm score. In the control and study groups, 21.4% of patients (6 of 28) and 48.4% of patients (15 of 31), respectively, returned to their preinjury sports activity levels (P = .031). At last follow-up, the mean side-to-side difference in posterior laxity was significantly improved in the study group compared with the control group (1.52 ± 0.70 mm in study group vs 3.17 ± 2.01 mm in control group, P < .01). CONCLUSIONS: Primary isolated PCLR with suture tape augmentation provides better posterior stability than PCLR without suture tape augmentation at a minimum of 2 years' follow-up. No differences between the groups were observed in the percentage of patients who met or exceeded the MCID for the subjective IKDC and Lysholm scores. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Mechanism of chromosomal mosaicism in preimplantation embryos and its effect on embryo development.

Aneuploidy is one of the main causes of miscarriage and in vitro fertilization failure. Mitotic abnormalities in preimplantation embryos are the main cause of mosaicism, which may be influenced by several endogenous factors such as relaxation of cell cycle control mechanisms, defects in chromosome cohesion, centrosome aberrations and abnormal spindle assembly, and DNA replication stress. In addition, incomplete trisomy rescue is a rare cause of mosaicism. However, there may be a self-correcting mechanism in mosaic embryos, which allows some mosaicisms to potentially develop into normal embryos. At present, it is difficult to accurately diagnose mosaicism using preimplantation genetic testing for aneuploidy. Therefore, in clinical practice, embryos diagnosed as mosaic should be considered comprehensively based on the specific situation of the patient.

Quantum Plexcitonic Sensing.

While fundamental to quantum sensing, quantum state control has been traditionally limited to extreme conditions. This restricts the impact of the practical implementation of quantum sensing on a broad range of physical measurements. Plexcitons, however, provide a promising path under ambient conditions toward quantum state control and thus quantum sensing, owing to their origin from strong plasmon-exciton coupling. Herein, we harness plexcitons to demonstrate quantum plexcitonic sensing by strongly coupling excitonic particles to a plasmonic hyperbolic metasurface. As compared to classical sensing in the weak-coupling regime, our model of quantum plexcitonic sensing performs at a level that is ∼40 times more sensitive. Noise-modulated sensitivity studies reinforce the quantum advantage over classical sensing, featuring better sensitivity, smaller sensitivity uncertainty, and higher resilience against optical noise. The successful demonstration of quantum plexcitonic sensing opens the door for a variety of physical, chemical, and biological measurements by leveraging strongly coupled plasmon-exciton systems.

Plasmonic Nanodiamonds.

While nitrogen-vacancy (NV) centers in diamonds have emerged as promising solid-state quantum emitters for sensing applications, the tantalizing possibility of coupling them with photonic or broadband plasmonic nanostructures to create ultrasensitive biolabels has not been fully realized. Indeed, it remains technologically challenging to create free-standing hybrid diamond-based imaging nanoprobes with enhanced brightness and high temporal resolution. Herein, we leverage the bottom-up DNA self-assembly to develop hybrid free-standing plasmonic nanodiamonds, which feature a closed plasmonic nanocavity completely encapsulating a single nanodiamond. Correlated single nanoparticle spectroscopical characterizations suggest that the plasmonic nanodiamond displays dramatically and simultaneously enhanced brightness and emission rate. We believe that they hold huge potential to serve as a stable solid-state single-photon source and could serve as a versatile platform to study nontrivial quantum effects in biological systems with enhanced spatial and temporal resolution.