Integrative Metabolomics and Proteomics Allow the Global Intracellular Characterization of Bacillus subtilis Cells and Spores.

Reliable and comprehensive multi-omics analysis is essential for researchers to understand and explore complex biological systems more completely. Bacillus subtilis (B. subtilis) is a model organism for Gram-positive spore-forming bacteria, and in-depth insight into the physiology and molecular basis of spore formation and germination in this organism requires advanced multilayer molecular data sets generated from the same sample. In this study, we evaluated two monophasic methods for polar and nonpolar compound extraction (acetonitrile/methanol/water; isopropanol/water, and 60% ethanol) and two biphasic methods (chloroform/methanol/water, and methyl tert-butyl ether/methanol/water) on coefficients of variation of analytes, identified metabolite composition, and the quality of proteomics profiles. The 60% EtOH protocol proved to be the easiest in sample processing and was more amenable to automation. Collectively, we annotated 505 and 484 metabolites and identified 1665 and 1562 proteins in B. subtilis vegetative cells and spores, respectively. We also show differences between vegetative cells and spores from a multi-omics perspective and demonstrate that an integrative multi-omics analysis can be implemented from one sample using the 60% EtOH protocol. The results obtained by the 60% EtOH protocol provide comprehensive insight into differences in the metabolic and protein makeup of B. subtilis vegetative cells and spores.

Melatonin suppresses TLR4-mediated RSV infection in the central nervous cells by inhibiting NLRP3 inflammasome formation and autophagy.

Respiratory syncytial virus (RSV) infects neuronal cells in the central nervous system (CNS), resulting in neurological symptoms. In the present study, we intended to explore the mechanism of RSV infection-induced neuroinflammatory injury from the perspective of the immune response and sought to identify effective protective measures against the injury. The findings showed that toll-like receptor 4 (TLR4) was activated after RSV infection in human neuronal SY5Y cells. Furthermore, TLR4 activation induced autophagy and apoptosis in neuronal cells, promoted the formation of the NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, and increased the secretion of downstream inflammatory cytokines such as interleukin-1ß (IL-1ß), interleukin-18 (IL-18) and tumour necrosis factor-α (TNF-α). Interestingly, blockade of TLR4 or treatment with exogenous melatonin significantly suppressed TLR4 activation as well as TLR4-mediated apoptosis, autophagy and immune responses. Therefore, we infer that melatonin may act on the TLR4 to ameliorate RSV-induced neuronal injury, which provides a new therapeutic target for RSV infection.

Diminishing warming effects on plant phenology over time.

Plant phenology, the timing of recurrent biological events, shows key and complex response to climate warming, with consequences for ecosystem functions and services. A key challenge for predicting plant phenology under future climates is to determine whether the phenological changes will persist with more intensive and long-term warming. Here, we conducted a meta-analysis of 103 experimental warming studies around the globe to investigate the responses of four phenophases - leaf-out, first flowering, last flowering, and leaf coloring. We showed that warming advanced leaf-out and flowering but delayed leaf coloring across herbaceous and woody plants. As the magnitude of warming increased, the response of most plant phenophases gradually leveled off for herbaceous plants, while phenology responded in proportion to warming in woody plants. We also found that the experimental effects of warming on plant phenology diminished over time across all phenophases. Specifically, the rate of changes in first flowering for herbaceous species, as well as leaf-out and leaf coloring for woody species, decreased as the experimental duration extended. Together, these results suggest that the real-world impact of global warming on plant phenology will diminish over time as temperatures continue to increase.

TLR4 TIR domain and nucleolin GAR domain synergistically mediate RSV infection and induce neuronal inflammatory damage in SH-SY5Y cells.

Previous research results of our group showed that Toll-like receptor 4 (TLR4) and nucleolin synergistically mediate respiratory syncytial virus (RSV) infection in human central neuron cells, but the specific mechanism remains unclear. Here we designed and synthesized lentiviruses with TIR (674-815 aa), TLR4 (del 674-815 aa), GAR (645-707 aa), and NCL (del 645-707 aa) domains, and obtained stable overexpression cell lines by drug screening, and subsequently infected RSV at different time points. Laser confocal microscopy and coimmunoprecipitation were used for the observation of co-localization and interaction of TIR/GAR domains. Western blot analysis was used for the detection of p-NF-κB and LC3 protein expression. Real-time PCR was used for the detection of TLR4/NCL mRNA expression. ELISA assay was used to measure IL-6, IL-1ß, and TNF-α concentrations and flow cytometric analysis was used for the study of apoptosis. Our results suggest that overexpression of TIR and GAR domains can exacerbate apoptosis and autophagy, and that TIR and GAR domains can synergistically mediate RSV infection and activate the NF-κB signaling pathway, which regulates the secretion of downstream inflammatory factors, such as IL-6, IL-1ß, and TNF-α, and ultimately leads to neuronal inflammatory injury.

Enhanced Recovery Protocol Versus Conventional Care in Patients Undergoing Esophagectomy for Cancer: Advantages in Clinical and Patient-Reported Outcomes.

BACKGROUND: This study was designed to compare the clinical and patient-reported outcomes (PROs) between the enhanced recovery after surgery (ERAS) protocol and conventional care in patients undergoing esophagectomy for cancer, which have not previously been compared. METHODS: This single-center retrospective study included prospective PRO data from August 2019 to June 2021. Clinical outcomes included perioperative complications and postoperative length of stay (PLOS). Patient-reported outcomes were assessed by using the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire Core-30 (QLQ-C30) and esophagus-specific module (QLQ-OES18) preoperatively to 6 months postoperatively. Mixed-effects models were used to longitudinally compare quality of life (QOL) scores between the two modes. RESULTS: Patients undergoing conventional care and ERAS were analyzed (n = 348 and 109, respectively). The ERAS group had fewer overall complications, pneumonia, arrhythmia, and a shorter PLOS than the conventional group, and outperformed the conventional group in five functional QLQ-C30 domains and five symptom QLQ-OES18 domains, including less dysphagia (p < 0.0001), trouble talking (p = 0.0006), and better eating (p < 0.0001). These advantages persisted for 3 months postoperatively. For the cervical circular stapled anastomosis, the initial domains and duration of benefit were reduced in the ERAS group. CONCLUSIONS: The ERAS protocol has significant advantages over conventional care in terms of clinical outcomes, lowering postoperative symptom burden, and improving functional QOL in patients who have undergone esophagectomy. Selection of the optimal technique for cervical anastomosis is a key operative component of ERAS that maintains the symptom domains and duration of the advantages of PROs.

Theory of Defect-Induced Crystal Field Perturbations in Rare-Earth Magnets.

We present a theory describing the single-ion anisotropy of rare-earth (RE) magnets in the presence of point defects. Taking the RE-lean 1∶12 magnet class as a prototype, we use first-principles calculations to show how the introduction of Ti substitutions into SmFe_{12} perturbs the crystal field, generating new coefficients due to the lower symmetry of the RE environment. We then demonstrate that these perturbations can be described extremely efficiently using a screened point charge model. We provide analytical expressions for the anisotropy energy that can be straightforwardly implemented in atomistic spin dynamics simulations, meaning that such simulations can be carried out for an arbitrary arrangement of point defects. The significant crystal field perturbations calculated here demonstrate that a sample that is single phase from a structural point of view can nonetheless have a dramatically varying anisotropy profile at the atomistic level if there is compositional disorder, which may influence localized magnetic objects like domain walls or skyrmions.

Identification of Sulfur-Containing Chlorinated Paraffin Structural Analogues in Human Serum: Origination from Biotransformation or Bioaccumulation?

Chlorinated paraffins (CPs) are manufactured and used in high quantities and have diverse structural analogues. It is generally recognized that sulfur-containing structural analogues of CPs are mainly derived from sulfate-conjugated phase II metabolism. In this study, we non-targeted identified three classes of sulfur-containing CP structural analogues (CPs-S) in human serum, including 44 CP sulfates (CPs-SO4H/CPs-SO4H-OH), 14 chlorinated benzene sulfates (CBs-SO4H), and 19 CP sulfite esters (CPs-SO3/CPs-S2O6), which were generated during the production of commercial mixtures of CPs and, thus, bioaccumulated via environmental exposures. We first wrote a program to screen CPs-S, which were baseline-separated from CPs according to their polar functional groups. Then, mass spectral analyses of alkalization-acidification liquid-liquid extracts of serum samples and Orbitrap mass spectrometry analyses in the presence and absence of tetraphenylphosphonium chloride (Ph4PCl), respectively, were performed to determine the ionization forms ([M + Cl]- or [M - H]-) of CPs-S. The presence of fragment ions (SO4H-, SO3-, SO2Cl-, and HSO3-) revealed the structures of CPs-S, which were validated by their detections in commercial mixtures of CPs. The estimated total concentrations of CPs-S in the human serum samples were higher than the concentrations of medium- and long-chain CPs. The profiles of CPs-S in human serum were similar to those detected in CP commercial mixtures and rats exposed to the commercial mixtures, but CPs-S were not detected in human liver S9 fractions or rat tissues after exposure to CP standards. These results, together with the knowledge of the processes used to chemically synthesize CPs, demonstrate that CPs-S in humans originates from environmental bioaccumulation.

Analysis of Risk Factors for Velopharyngeal Insufficiency and Palatal Fistula After Sommerlad-Furlow Palatoplasty.

This study aimed to introduce a surgery technique-Sommerlad-Furlow palatoplasty (SFP) and analyze the risk factors of velopharyngeal insufficiency (VPI) and palatal fistula after SFP. Cases after SFP under the age of 5 between 2011 and 2021 were reviewed, and the cases with complete follow-up information were included. Univariate and multivariate logistic regression were used to evaluate the effects of surgical age, surgery technique, surgeon's experience, and cleft type on velopharyngeal function and the occurrence of palatal fistula. SFP is a safe and effective procedure to increase the palatal length and reconstruct the levator veli palatini sling. The speech outcome after SFP was associated with cleft type and age at operation. Age = 1.285 years is the best cutoff value. The fistula occurrence was associated with cleft type only.

Electronic-Structure-Modulated Cu,Co-Coanchored N-Doped Nanocarbon as a Difunctional Electrocatalyst for Hydrogen Evolution and Oxygen Reduction Reactions.

To alleviate the problems of environmental pollution and energy crisis, aggressive development of clean and alternative energy technologies, in particular, water splitting, metal-air batteries, and fuel cells involving two key half reactions comprising hydrogen evolution reaction (HER) and oxygen reduction (ORR), is crucial. In this work, an innovative hybrid comprising heterogeneous Cu/Co bimetallic nanoparticles homogeneously dispersed on a nitrogen-doped carbon layer (Cu/Co/NC) was constructed as a bifunctional electrocatalyst toward HER and ORR via a hydrothermal reaction along with post-solid-phase sintering technique. Thanks to the interfacial coupling and electronic synergism between the Cu and Co bimetallic nanoparticles, the Cu/Co/NC catalyst showed improved catalytic ORR activity with a half-wave potential of 0.865 V and an excellent stability of more than 30 h, even compared to 20 wt% Pt/C. The Cu/Co/NC catalyst also exhibited excellent HER catalytic performance with an overpotential of below 149 mV at 10 mA/cm2 and long-term operation for over 30 h.

Development and implementation of evidence-based, nurse-leading early warning model and healthcare quality improvement project for transplant-associated thrombotic microangiopathy: a mixed-methods, before-and-after study.

OBJECTIVE: The early identification and diagnosis of transplant-associated thrombotic microangiopathy (TA-TMA) are essential yet difficult in patients underwent hematopoietic stem cell transplantation (HSCT). To develop an evidence-based, nurse-leading early warning model for TA-TMA, and implement the healthcare quality review and improvement project. METHODS: This study was a mixed-methods, before-and-after study. The early warning model was developed based on quality evidence from literature search. The healthcare quality review and improvement project mainly included baseline investigation of nurse, improvement action and effectiveness evaluation. The awareness and knowledge of early parameter of TA-TMA among nurses and the prognosis of patients underwent HSCT were compared before and after the improvement. RESULTS: A total of 1 guideline, 1 evidence synthesis, 4 expert consensuses, 10 literature reviews, 2 diagnostic studies, and 9 case series were included in the best evidence. The early warning model including warning period, high-risk characteristics and early manifestation of TA-TMA was developed. The improvement action, including staff training and assessment, suspected TA-TMA identification and patient education, was implemented. The awareness and knowledge rate of early parameter of TA-TMA among nurses significantly improved after improvement action (100% vs. 26.7%, P < 0.001). The incidence of TA-TMA was similar among patients underwent HSCT before and after improvement action (2.8% vs. 1.2%, P = 0.643), while no fall event occurred after improvement action (0 vs. 1.2%, P < 0.001). CONCLUSION: The evidence-based early warning model and healthcare quality improvement project could enhance the awareness and knowledge of TA-TMA among healthcare providers and might improve the prognosis of patients diagnosed with TA-TMA.

Exploring the efficacy of subwavelength gratings as short-wavelength infrared filters.

Advancements in nanofabrication technology have greatly facilitated research on nanostructures and their associated properties. Among these structures, subwavelength components have emerged as promising candidates for ultra-compact optical elements, can potentially supplant conventional optical components and enable the realization of compact and efficient optical devices. Spectral analysis within the infrared spectrum offers a wealth of information for monitoring crop health, industrial processes, and target identification. However, conventional spectrometers are typically bulky and expensive, driving an increasing demand for cost-effective spectral sensors. Here we investigate three distinct subwavelength grating structures designed to function as narrowband filters within the short-wavelength infrared (SWIR) range. Through simple adjustments to the period of grating strips, these filters selectively transmit light across a wide wavelength range from 1100 to 1700 nm with transmission exceeding 70% and full width at half maximum (FWHM) down to 6 nm. Based on a simple design, the results present great potential of subwavelength grating filters for multiband integration and developing ultra-compact spectral sensors.

Research on the Human Motion Recognition Method Based on Wearable.

The accurate analysis of human dynamic behavior is very important for overcoming the limitations of movement diversity and behavioral adaptability. In this paper, a wearable device-based human dynamic behavior recognition method is proposed. The method collects acceleration and angular velocity data through a six-axis sensor to identify information containing specific behavior characteristics in a time series. A human movement data acquisition platform, the DMP attitude solution algorithm, and the threshold algorithm are used for processing. In this experiment, ten volunteers wore wearable sensors on their bilateral forearms, upper arms, thighs, calves, and waist, and movement data for standing, walking, and jumping were collected in school corridors and laboratory environments to verify the effectiveness of this wearable human movement recognition method. The results show that the recognition accuracy for standing, walking, and jumping reaches 98.33%, 96.67%, and 94.60%, respectively, and the average recognition rate is 96.53%. Compared with similar methods, this method not only improves the recognition accuracy but also simplifies the recognition algorithm and effectively saves computing resources. This research is expected to provide a new perspective for the recognition of human dynamic behavior and promote the wider application of wearable technology in the field of daily living assistance and health management.

Electrochemical sulfate production from sulfide-containing wastewaters and integration with electrochemical nitrogen recovery.

Electrochemical methods can help manage sulfide in wastewater, which poses environmental and health concerns due to its toxicity, malodor, and corrosiveness. In addition, sulfur could be recovered as fertilizer and commodity chemicals from sulfide-containing wastewaters. Wastewater characteristics vary widely among wastewaters; however, it remains unclear how these characteristics affect electrochemical sulfate production. In this study, we evaluated how four characteristics of influent wastewaters (electrolyte pH, composition, sulfide concentration, and buffer strength) affect sulfide removal (sulfide removal rate, sulfide removal efficiency) and sulfate production metrics (sulfate production rate, sulfate production selectivity). We identified that electrolyte pH (3 × difference, i.e., 25.1 to 84.9 µM h-1 in average removal rate within the studied pH range) and sulfide concentration (16 × difference, i.e., 82.1 to 1347.2 µM h-1 in average removal rate) were the most influential factors for electrochemical sulfide removal. Sulfate production was most sensitive to buffer strength (6 × difference, i.e., 4.4 to 27.4 µM h-1 in average production rate) and insensitive to electrolyte composition. Together, these results provide recommendations for the design of wastewater treatment trains and the feasibility of applying electrochemical methods to varying sulfide-containing wastewaters. In addition, we investigated a simultaneous multi-nutrient (sulfur and nitrogen) process that leverages electrochemical stripping to further enhance the versatility and compatibility of electrochemical nutrient recovery.

Negative Effects of Butachlor on the Growth and Physiology of Four Aquatic Plants.

The increasing use of herbicides in intelligent agricultural production is driven by the time-consuming nature of manual weeding, as well as its ephemeral effectiveness. However, herbicides like butachlor degrade slowly and can be washed away by rainwater, ultimately flowing into the farm ponds and posing risks to aquatic plants. To identify and recommend superior restoration strategies that effectively address the challenges posed by butachlor, we investigated the impacts of butachlor on the growth and physiology of four common aquatic plants (i.e., Hydrilla verticillata, Ceratophyllum demersum, Potamogeton maackianus, and Myriophyllum aquaticum) and their potential role in mitigating environmental damage by reducing residual herbicide levels. Our findings indicated that M. aquaticum was tolerant to butachlor, exhibiting higher growth rates than other species when exposed to various butachlor concentrations. However, the concentration of butachlor negatively impacted the growth of H. verticillata, C. demersum, and P. maackianus, with higher concentrations leading to more significant inhibitory effects. After a 15-day experimental period, aquatic plants reduced the butachlor residuals in culture mediums across concentrations of 0.5 mg/L, 1 mg/L, and 2 mg/L compared to non-plant controls. Our findings classified P. maackianus as butachlor-sensitive and M. aquaticum as butachlor-tolerant species. This investigation represents novel research aimed at elucidating the contrasting effects of different concentrations of butachlor on four common aquatic species in the agricultural multi-pond system.

Quaternization drives spleen-to-lung tropism conversion for mRNA-loaded lipid-like nanoassemblies.

Background: As the overwhelming majority of advanced mRNA delivery systems are preferentially accumulated in the liver, there is an accelerating growth in the demand for the development of non-liver mRNA delivery platforms. Methods: In this study, we prepared cationic lipid-like nanoassemblies through a N-quaternizing strategy. Their physicochemical properties, in vitro mRNA delivery efficiency, and organ tropism in mice were investigated. Results: Introduction of quaternary ammonium groups onto lipid-like nanoassemblies not only enhances their mRNA delivery performance in vitro, but also completely alters their tropism from the spleen to the lung after intravenous administration in mice. Quaternized lipid-like nanoassemblies exhibit ultra-high specificity to the lung and are predominantly taken up by pulmonary immune cells, leading to over 95% of exogenous mRNA translation in the lungs. Such mRNA delivery carriers are stable even after more than one-year storage at ambient temperature. Conclusions: Quaternization provides an alternative method for design of new lung-targeted mRNA delivery systems without incorporation of targeting ligands, which should extend the therapeutic applicability of mRNA to lung diseases.

A critical size volumetric muscle loss model in mouse masseter with impaired mastication on nutrition.

Orofacial muscle defect due to congenital anomalies, tumour ablation or traumatic accident that exceeds endogenous regeneration capacity may lead to sustained deficits in masticatory function and nutrition intake. Functional recovery has always been the goal of muscle tissue repair, but currently, there is no suitable model for quantitative analyses of either functional consequences or treatment efficacy of orofacial muscle defect. This study proposed a critical size volumetric muscle loss (VML) model in mouse masseter with impaired mastication on nutrition. Full-thickness VML defects in diameter of 1.0, 1.5, 2.0 and 3.0 mm were generated in the centre of the mouse masseter using a biopsy punch to determine the critical size for functional impairment. In the VML region, myogenesis was dampened but fibrogenesis was activated, as long with a reduction in the density of the neuromuscular junction and an increase in vascular density. Accordingly, persistent fibrosis was observed in the centre region of VML in all diameters. The 2.0 mm diameter was the critical threshold to masticatory function impairment after VML in the masseter. VML of 3.0 mm diameter led to a significant impact on nutrition intake and body weight gain. Autologous muscle graft effectively relieved the fibrosis and functional deficit after VML injury in the masseter. This model serves as a reliable tool in studying functional recovery strategies for orofacial muscle defects.

Dialdehyde cellulose (DAC) and polyethyleneimine (PEI) coated polyvinylidene fluoride (PVDF) membrane for simultaneously removing emulsified oils and anionic dyes.

Developing high-efficiency membrane for oil and dye removal is very urgent, because wastewater containing them can cause great damage to human and environment. In this study, a coated membrane was fabricated by applying DAC and PEI onto the commercial PVDF microfiltration membrane for supplying the demand. The coated membrane presents superhydrophlic and superoleophobic properties with a water contact angle of 0o and underwater oil contact angle exceed 150°, as well as excellent low underwater oil adhesion performance. The coated membrane shows high separation efficiency exceeded 99.0% and flux 350.0 L·m-2·h-1 when used for separating for six kinds of oil including pump oil, sunflower oil, n-hexadecane, soybean oil, diesel and kerosene in water emulsions. Additionally, the coated membrane can effectively remove anionic dyes, achieving rejection rates of 94.7%, 93.4%, 92.3%, 90.7% for the CR, MB, RB5, AR66, respectively. More importantly, the membrane was able to simultaneously remove emulsified oil and soluble anionic dyes in wastewater containing both of them. Therefore, this novel coated membrane can be a promising candidate for treating complex wastewater.

XIOSIS: an X-ray-based intra-operative image-guided platform for oncology smart material delivery.

Image-guided interventional oncology procedures can greatly enhance the outcome of cancer treatment. As an enhancing procedure, oncology smart material delivery can increase cancer therapy's quality, effectiveness, and safety. However, the effectiveness of enhancing procedures highly depends on the accuracy of smart material placement procedures. Inaccurate placement of smart materials can lead to adverse side effects and health hazards. Image guidance can considerably improve the safety and robustness of smart material delivery. In this study, we developed a novel generative deep-learning platform that highly prioritizes clinical practicality and provides the most informative intra-operative feedback for image-guided smart material delivery. XIOSIS generates a patient-specific 3D volumetric computed tomography (CT) from three intraoperative radiographs (X-ray images) acquired by a mobile C-arm during the operation. As the first of its kind, XIOSIS (i) synthesizes the CT from small field-of-view radiographs;(ii) reconstructs the intra-operative spacer distribution; (iii) is robust; and (iv) is equipped with a novel soft-contrast cost function. To demonstrate the effectiveness of XIOSIS in providing intra-operative image guidance, we applied XIOSIS to the duodenal hydrogel spacer placement procedure. We evaluated XIOSIS performance in an image-guided virtual spacer placement and actual spacer placement in two cadaver specimens. XIOSIS showed a clinically acceptable performance, reconstructed the 3D intra-operative hydrogel spacer distribution with an average structural similarity of 0.88 and Dice coefficient of 0.63 and with less than 1 cm difference in spacer location relative to the spinal cord.