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Implant-associated Staphylococcus aureus (S. aureus) osteomyelitis is a severe challenge in orthopedics. While antibiotic-loaded bone cement is a standardized therapeutic approach for S. aureus osteomyelitis, it falls short in eradicating Staphylococcus abscess communities (SACs) and bacteria within osteocyte-lacuna canalicular network (OLCN) and repairing bone defects. To address limitations, we developed a borosilicate bioactive glass (BSG) combined with ferroferric oxide (Fe3O4) magnetic scaffold to enhance antibacterial efficacy and bone repair capabilities. We conducted comprehensive assessments of the osteoinductive, immunomodulatory, antibacterial properties, and thermal response of this scaffold, with or without an alternating magnetic field (AMF). Utilizing a well-established implant-related S. aureus tibial infection rabbit model, we evaluated its antibacterial performance in vivo. RNA transcriptome sequencing demonstrated that BSG + 5%Fe3O4 enhanced the immune response to bacteria and promoted osteogenic differentiation and mineralization of MSCs. Notably, BSG + 5%Fe3O4 upregulated gene expression of NOD-like receptor and TNF pathway in MSCs, alongside increased the expression of osteogenic factors (RUNX2, ALP and OCN) in vitro. Flow cytometry on macrophage exhibited a polarization effect towards M2, accompanied by upregulation of anti-inflammatory genes (TGF-β1 and IL-1Ra) and downregulation of pro-inflammatory genes (IL-6 and IL-1β) among macrophages. In vivo CT imaging revealed the absence of osteolysis and periosteal response in rabbits treated with BSG + 5%Fe3O4 + AMF at 42 days. Histological analysis indicated complete controls of SACs and bacteria within OLCN by day 42, along with new bone formation, signifying effective control of S. aureus osteomyelitis. Further investigations will focus on the in vivo biosafety and biological mechanism of this scaffold within infectious microenvironment.

Abstract Parkinson’s disease (PD) exhibits heterogeneity in terms of symptoms and prognosis, likely due to diverse neuroanatomical alterations. This study employs a contrastive deep learning approach to analyze Magnetic Resonance Imaging (MRI) data from 932 PD patients and 366 controls, aiming to disentangle PD-specific neuroanatomical alterations. The results reveal that these neuroanatomical alterations in PD are correlated with individual differences in dopamine transporter binding deficit, neurodegeneration biomarkers, and clinical severity and progression. The correlation with clinical severity is verified in an external cohort. Notably, certain proteins in the cerebrospinal fluid are strongly associated with PD-specific features, particularly those involved in the immune function. The most notable neuroanatomical alterations are observed in both subcortical and temporal regions. Our findings provide deeper insights into the patterns of brain atrophy in PD and potential underlying molecular mechanisms, paving the way for earlier patient stratification and the development of treatments to slow down neurodegeneration.

Introduction: There was limited research on the epidemiology of hyperphosphatemia in early-stage chronic kidney disease (CKD) patients. We aimed to explore the clinical characteristics and prognostic value of hyperphosphatemia in patients with CKD stages 1–2. Methods: We enrolled adult patients with CKD stages 1–2 from 24 regional central hospitals across China. Hyperphosphatemia was defined as a serum phosphate level exceeding 1.45 mmol/L. The study outcomes included all-cause and cardiovascular (CV) mortality. Cox proportional hazard models were used to investigate the association of hyperphosphatemia with all-cause and CV mortality. Results: Among 99,266 patients with CKD stages 1–2 across China, the prevalence of hyperphosphatemia was 8.3%. The prevalence of hyperphosphatemia was increased with the level of urinary protein and was higher in younger and female patients. Among 63,121 patients with survival information, during a median of 5.2 years follow-up period, there were 436 (8.0%) and 4,695 (8.1%) deaths in those with and without hyperphosphatemia, respectively. After adjusting for potential confounders, compared with patients without hyperphosphatemia, patients with hyperphosphatemia were associated with a higher risk of all-cause mortality (hazard ratio: 1.28, 95% CI: 1.16–1.41). Although nearly 60.3% of hyperphosphatemia could be relieved without phosphate-lowering drug therapy among patients with CKD stages 1–2, transient hyperphosphatemia was also associated with an increased risk of all-cause mortality (p = 0.048). Conclusions: Hyperphosphatemia was not rare in patients with CKD stages 1–2 and was associated with an increased risk of mortality. Clinicians should closely monitor serum phosphorus levels in patients with CKD, even in those with normal kidney function.

Abstract The monitoring of currents in the abyssal ocean is an essential foundation of deep-sea research. The state-of-the-art current meter has limitations such as the requirement of a power supply for signal transduction, low pressure resistance, and a narrow measurement range. Here, we report a fully integrated, self-powered, highly sensitive deep-sea current measurement system in which the ultra-sensitive triboelectric nanogenerator harvests ocean current energy for the self-powered sensing of tiny current motions down to 0.02 m/s. Through an unconventional magnetic coupling structure, the system withstands immense hydrostatic pressure exceeding 45 MPa. A variable-spacing structure broadens the measuring range to 0.02–6.69 m/s, which is 67% wider than that of commercial alternatives. The system successfully operates at a depth of 4531 m in the South China Sea, demonstrating the record-deep operations of triboelectric nanogenerator-based sensors in deep-sea environments. Our results show promise for sustainable ocean current monitoring with higher spatiotemporal resolution.

Abstract Brain function is vulnerable to the consequences of inadequate sleep, an adverse trend that is increasingly prevalent. The REM sleep phase has been implicated in coordinating various brain structures and is hypothesized to have potential links to brain variability. However, traditional imaging research have encountered challenges in attributing specific brain region activity to REM sleep, remained understudied at the whole-brain connectivity level. Through the spilt-night paradigm, distinct patterns of REM sleep phases were observed among the full-night sleep group (n = 36), the early-night deprivation group (n = 41), and the late-night deprivation group (n = 36). We employed connectome-based predictive modeling (CPM) to delineate the effects of REM sleep deprivation on the functional connectivity of the brain (REM connectome) during its resting state. The REM sleep-brain connectome was characterized by stronger connectivity within the default mode network (DMN) and between the DMN and visual networks, while fewer predictive edges were observed. Notably, connections such as those between the cingulo-opercular network (CON) and the auditory network, as well as between the subcortex and visual networks, also made significant contributions. These findings elucidate the neural signatures of REM sleep loss and reveal common connectivity patterns across individuals, validated at the group level.

Abstract Background This work aimed to investigate the change in fingerprint depth and the recovery rule of fingerprint biological recognition function after repairing finger abdominal defects and rebuilding fingerprint with a free flap. Method From April 2018 to March 2023, we collected a total of 43 cases of repairing finger pulp defects using the free flap of the fibular side of the great toe with the digital nerve. After surgery, irregular follow-up visits were conducted to observe fingerprint clarity, perform the ninhydrin test or detect visible sweating with the naked eye. We recorded fingerprint clarity, nail shape, two-point discrimination, cold perception, warm perception and fingerprint recognition using smartphones. The reconstruction process of the repaired finger was recorded to understand the changes in various observation indicators and their relationship with the depth of the fingerprint. The correlation between fingerprint depth and neural repair was determined, and the process of fingerprint biological recognition function repair was elucidated. Result All flaps survived, and we observed various manifestations in different stages of nerve recovery. The reconstructed fingerprint had a clear fuzzy process, and the depth changes of the fingerprint were consistent with the changes in the biological recognition function curve. Conclusion The free flap with the digital nerve is used to repair finger pulp defects. The reconstructed fingerprint has a biological recognition function, and the depth of the fingerprint is correlated with the process of nerve repair. The fingerprint morphology has a dynamic recovery process, and it can reach a stable state after 6–8 months.

Sleep deprivation has been demonstrated to exert widespread and intricate impacts on the brain network. The human brain network is a modular network composed of interconnected nodes. This network consists of provincial hubs and connector hubs, with provincial hubs having diverse connectivities within their own modules, while connector hubs distribute their connectivities across different modules. The latter is crucial for integrating information from various modules and ensuring the normal functioning of the modular brain. However, there has been a lack of systematic investigation into the impact of sleep deprivation on brain connector hubs. In this study, we utilized functional connectivity from resting-state functional magnetic resonance imaging, as well as structural connectivity from diffusion-weighted imaging, to systematically explore the variation of connector hub properties in the cerebral cortex after one night of sleep deprivation. The normalized participation coefficients (PCnorm) were utilized to identify connector hubs. In both the functional and structural networks, connector hubs exhibited a significant increase in average PCnorm, indicating the diversity enhancement of the connector hub following sleep deprivation. This enhancement is associated with increased network cost, reduced modularity, and decreased small-worldness, but enhanced global efficiency. This may potentially signify a compensatory mechanism within the brain following sleep deprivation. The significantly affected connector hubs were primarily observed in both the Control Network and Salience Network. We believe that the observed results reflect the increasing demand on the brain to invest more effort at preventing performance deterioration after sleep loss, in exchange for increased communication efficiency, especially involving systems responsible for neural resource allocation and cognitive control. These results have been replicated in an independent dataset. In conclusion, this study has enhanced our understanding of the compensatory mechanism in the brain response to sleep deprivation. This compensation is characterized by an enhancement in the connector hubs responsible for inter-modular communication, especially those related to neural resource and cognitive control. As a result, this compensation comes with a higher network cost but leads to an improvement in global communication efficiency, akin to a more random-like network manner.

Abstract Background Quantitative computed tomography (QCT)-based lumbar bone mineral density (LBMD) has been used to diagnose osteoporosis. This study explored the value of lower thoracic BMD (TBMD) in diagnosing osteoporosis in older adults during CT lung cancer screening. Methods This study included 751 subjects who underwent QCT scans with both LBMD and TBMD. 141 of them was selected for a validation. Osteoporosis was diagnosed based on LBMD using the ACR criteria (gold standard). TBMD thresholds were obtained using receiver operating characteristic curve. TBMD was also translated into LBMD (TTBMD) and osteoporosis was defined based on TTBMD using ACR criteria. The performance of TBMD and TTBMD in identifying osteoporosis was determined by Kappa test. The associations between TBMD- and TTBMD-based osteoporosis and fracture were tested in 227 subjects with followed up status of spine fracture. Results The performance of TBMD in identifying osteoporosis was low (kappa = 0.66) if using the ACR criteria. Two thresholds of TBMD for identifying osteopenia (128 mg/cm3) and osteoporosis (91 mg/cm3) were obtained with areas under the curve of 0.97 and 0.99, respectively. The performance of the identification of osteoporosis/osteopenia using the two thresholds or TTBMD both had good agreement with the gold standard (kappa = 0.78, 0.86). Similar results were observed in validation population. Osteoporosis identified using the thresholds (adjusted hazard ratio (HR) = 18.72, 95% confidence interval (CI): 5.13–68.36) or TTBMD (adjusted HR = 10.28, 95% CI: 4.22–25.08) were also associated with fractures. Conclusion Calculating the threshold of TBMD or normalizing TBMD to LBMD are both useful in identifying osteoporosis in older adults during CT lung cancer screening.

Abstract Total knee arthroplasty (TKA) is the most cost-effective, and potent method for the treatment of end-stage knee osteoarthritis. Acute normovolemic haemodilution (ANH) can effectively replace the need for allogeneic transfusions due to the high amount of bleeding during TKA. However, more studies are needed to prove the efficacy and safety of ANH and to clarify its indications in the field of knee replacement. Medical records from June 1, 2019 to June 1, 2021 were searched and grouped according to inclusion and exclusion criteria. PART I: 58 patients with ANH during TKA were selected as the ANH group (n = 58), and 58 patients with allogeneic transfusion were chosen as the control group (n = 58). PART II: Patients with anaemia were divided into the ANH group (n = 18) and the control group (n = 12). PART I: The postoperative inflammatory index and serum albumin in the ANH group were significantly lower than those in the control group. No significant difference was observed in the theoretical loss of red blood cells, postoperative renal function, liver function, cardiac function and biochemical ion index between the two groups. The effective rate of ANH in the normal haemoglobin group was significantly lower than that in the anaemia group. PART II: In patients with anaemia, the theoretical loss of red blood cells in patients with ANH was less than that in the control group. The postoperative inflammation, renal function, liver function and cardiac function in the ANH group were better than those in the control group, and no significant difference was noted in biochemical ions and nutritional status indicators. This paper shows that ANH not only can replace allogeneic transfusion in TKA, especially in patients with anaemia, but also has lower inflammatory indicators than allogeneic transfusion. From a security perspective, the body’s tolerance to ANH is within the body’s compensation range.

Multiple myeloma (MM) is the most prevalent malignant monoclonal disease of plasma cells. There is mounting evidence that interactions with the bone marrow (BM) niche are essential for the differentiation, proliferation, survival, migration, and treatment resistance of myeloma cells. For this reason, gaining a deeper comprehension of how BM microenvironment compartments interact with myeloma cells may inspire new therapeutic ideas that enhance patient outcomes. This review will concentrate on the most recent findings regarding the mechanisms of interaction between microenvironment and MM and highlight research on treatment targeting the BM niche.

ABSTRACT Pseudomonas can lead to peritoneal dialysis-associated peritonitis, which is characterized by a poor prognosis, such as a substantial failure rate and a high death rate. This study aimed to provide an overview of Pseudomonas peritonitis’s clinical features, the regimens of antibiotic, antibiotic resistance, and outcomes in peritoneal dialysis (PD) patients. This study observed patients with Pseudomonas peritonitis in two large PD centers in South China from January 2008 to December 2022. The demographics, symptomatology, antibiotics regimens, resistance to common antibiotics, and clinical outcomes of all included patients were reviewed. A total of 3,459 PD patients were included, among them 57 cases of peritonitis caused by Pseudomonas, including 48 cases (84.2%) of Pseudomonas aeruginosa. The incidence rate of Pseudomonas peritonitis was 0.0041 episode per patient-year. Of them, 28.1% (16 cases) of the patients were accompanied by exit site infection (ESI), and all had abdominal pain and turbid ascites at the time of onset. The most commonly used antibiotic combination was ceftazidime combined with amikacin. Approximately 89% of Pseudomonas species were sensitive to ceftazidime, and 88% were sensitive to amikacin. The overall primary response rate was 28.1% (16 patients), and the complete cure rate was 40.4% (23 patients). There was no significant difference in the complete cure rate of peritonitis using three and other antibiotic treatment regimens (44.8% vs 46.4%; P = 0.9). The successful treatment group had higher baseline albumin level (35.9 ± 6.2; P = 0.008) and residual urine volume (650.7 ± 375.5; P = 0.04). Although the incidence of peritonitis caused by Pseudomonas was low, the symptoms were serious, and prognosis was very poor. Pseudomonas was still highly susceptible to first-line antibiotics currently in use against Gram-negative bacteria. Patients with successful treatment had higher albumin levels and higher urine output.IMPORTANCEAlthough the incidence of peritoneal dialysis-associated peritonitis caused by Pseudomonas is very low, it seriously affects the technique survival of peritoneal dialysis patients. However, there are few studies and reports on Pseudomonas peritonitis in the Chinese mainland area. Therefore, the purpose of this study is to describe the clinical characteristics, the regimens of antibiotic, drug resistance, and outcome of peritoneal dialysis patients in southern China in the past 15 years and summarize the clinical experience in the treatment of Pseudomonas peritonitis.

With the intensification of the energy crisis and the global greenhouse effect, it is particularly necessary to develop renewable energy generation and reduce carbon emissions. Therefore, a low-carbon economic dispatch model of the electricity-gas-heat integrated energy system (IES) considering ladder-type carbon trading mechanism (LCTM), vehicles charging, and multimode utilization of hydrogen is proposed. A multimode utilization of hydrogen model in the IES is established and the model energy flow is analyzed. The vehicles charging demand is simulated by Monte Carlo, which provides a model to calculate the carbon emissions of vehicles. In addition, the ladder-type carbon trading mechanism and integrated demand response are introduced to improve the system economy and low carbon performance. The simulation results demonstrate that the proposed model can significantly reduce carbon emissions and improve the economy of the IES.

Abstract To ensure the safety and stability of the beach surface of the decommissioned uranium mill tailings pond, this paper uses red clay-bentonite and red clay (1:1) to carry out covering layer radon reduction simulation experiments to study the temperature, humidity, and radon reduction effect of the covering layer under natural conditions. The results show that the radon exhalation rate of red clay-bentonite cover layer is only 0.32 times that of red clay, which has a better radon reduction effect. The red clay-bentonite cover layer has better water retention and comparable heat preservation effect than red clay cover layer. The red clay-bentonite and red clay temperature curves follow the same evolution trend and were close together in the same outdoor conditions, and the humidity curves showed a difference of 1% to 3%. Soil temperature is the dominant factor affecting the variation of radon exhalation of red clay-bentonite and red clay covering layer with unsaturated water content.

In this study, a phase-field scheme that rigorously obeys conservation laws and irreversible thermodynamics is developed for modeling stress-corrosion coupled damage (SCCD). The coupling constitutive relationships of the deformation, phase-field damage, mass transfer, and electrostatic field are derived from the entropy inequality. The SCCD localization induced by secondary phases in Mg is numerically simulated using the implicit iterative algorithm of the self-defined finite elements. The quantitative evaluation of the SCCD of a C-ring is in good agreement with the experimental results. To capture the damage localization, a micro-galvanic corrosion domain is defined, and the buffering effect on charge migration is explored. Three cases are investigated to reveal the effect of localization on corrosion acceleration and provide guidance for the design for resistance to SCCD at the crystal scale.

Abstract Sarcopenia occurs in patients with Crohn's disease (CD). However, the association between sarcopenia and loss of response (LOR) to biologic agents remains unclear. This study explored such an association in CD patients. This retrospective study included 94 CD patients who received biologic therapy. The skeletal muscle cross‐sectional area at the third lumbar was assessed by computed tomography or magnetic resonance imaging for sarcopenia evaluation. A LOR was defined by fecal calprotectin (FC) 50% reduction from baseline levels or other factors, such as the used agent being replaced by other biologic agents. The association between sarcopenia and LOR was assessed by logistic regression analysis. LOR was observed in 54 patients (57.4%). The prevalence of sarcopenia in the LOR group was higher than that in response group (70.4% vs. 40.0%, p = 0.003). Sarcopenia (odds ratio [OR] = 3.89, 95% confidence interval [CI]: 1.31–11.54), Montreal L1 type (OR = 0.20, 95% CI: 0.06–0.60), perianal lesions (OR = 4.08, 95% CI: 1.31–12.70), and monocytes percentage (OR = 1.27, 95% CI: 1.02–1.57) at baseline were independent associated factors for LOR. Sarcopenia was also associated with LOR in patients who received infliximab (OR = 3.31, 95% CI: 1.11–9.87). Montreal L1 type, perianal lesions, and monocytes percentage (Model 1), and with additional consideration of sarcopenia (Model 2), were developed to predict LOR. Model 2 showed better performance than Model 1 (area under the curve [AUC] 0.82 vs. 0.75). Sarcopenia was associated with the LOR to biological agents or infliximab in adult patients with CD.

Abstract Eradication of MRSA osteomyelitis requires elimination of distinct biofilms. To overcome this, we developed bisphosphonate-conjugated sitafloxacin (BCS, BV600072) and hydroxybisphosphonate-conjugate sitafloxacin (HBCS, BV63072), which achieve “target-and-release” drug delivery proximal to the bone infection and have prophylactic efficacy against MRSA static biofilm in vitro and in vivo. Here we evaluated their therapeutic efficacy in a murine 1-stage exchange femoral plate model with bioluminescent MRSA (USA300LAC::lux). Osteomyelitis was confirmed by CFU on the explants and longitudinal bioluminescent imaging (BLI) after debridement and implant exchange surgery on day 7, and mice were randomized into seven groups: 1) Baseline (harvested at day 7, no treatment); 2) HPBP (bisphosphonate control for BCS) + vancomycin; 3) HPHBP (hydroxybisphosphonate control for HBCS) + vancomycin; 4) vancomycin; 5) sitafloxacin; 6) BCS + vancomycin; and 7) HBCS + vancomycin. BLI confirmed infection persisted in all groups except for mice treated with BCS or HBCS + vancomycin. Radiology revealed catastrophic femur fractures in all groups except mice treated with BCS or HBCS + vancomycin, which also displayed decreases in peri-implant bone loss, osteoclast numbers, and biofilm. To confirm this, we assessed the efficacy of vancomycin, sitafloxacin, and HBCS monotherapy in a transtibial implant model. The results showed complete lack of vancomycin efficacy while all mice treated with HBCS had evidence of infection control, and some had evidence of osseous integrated septic implants, suggestive of biofilm eradication. Taken together these studies demonstrate that HBCS adjuvant with standard of care debridement and vancomycin therapy has the potential to eradicate MRSA osteomyelitis.

Abstract Smoking of cigarettes among young adolescents is a pressing public health issue. However, the neural mechanisms underlying smoking initiation and sustenance during adolescence, especially the potential causal interactions between altered brain development and smoking behaviour, remain elusive. Here, using large longitudinal adolescence imaging genetic cohorts, we identify associations between left ventromedial prefrontal cortex (vmPFC) gray matter volume (GMV) and subsequent self-reported smoking initiation, and between right vmPFC GMV and the maintenance of smoking behaviour. Rule-breaking behaviour mediates the association between smaller left vmPFC GMV and smoking behaviour based on longitudinal cross-lagged analysis and Mendelian randomisation. In contrast, smoking behaviour associated longitudinal covariation of right vmPFC GMV and sensation seeking (especially hedonic experience) highlights a potential reward-based mechanism for sustaining addictive behaviour. Taken together, our findings reveal vmPFC GMV as a possible biomarker for the early stages of nicotine addiction, with implications for its prevention and treatment.

Extracting head waves and subsequently uploading their results from the downhole to the surface system in real time could improve the real-time guidance of ultrasonic imaging logging while drilling (UILWD) for drilling operations. To realize the downhole real-time extraction of head waves in this logging, three aspects were explored in this study. First, an improved energy ratio head-wave arrival extraction algorithm based on the weighting coefficients and characteristic functions, along with an amplitude detection method relying on peak-to-peak values, was proposed. Second, an echo reception pre-processing analog circuit and a digital signal processing circuit based on FPGA were designed. A pipeline algorithm was developed in FPGA to extract the arrival time and amplitude of the head wave. Finally, software simulations, laboratory tests, and field experiments related to this method were conducted. Our results showed that the real-time head-wave extraction method demonstrated a strong anti-noise ability in real time. The maximum relative error of the arrival time was less than 5%. The relative error of the amplitude was acceptable, and 90% of this value was within 5%. Through the measurement, the time of processing a single-channel waveform by a downhole algorithm was less than 15 ms, thus meeting the requirements for the real-time processing of downholes.

The outdoor thermal environment (OTE) is closely related to sustainable urban development and human living, and related research has attracted widespread attention. The research hotspots and research frontiers were obtained using CiteSpace to analyze 4473 relevant studies published in English from the Web of Science (WOS) core database from 1998 to 2023. The results show that (1) Hong Kong Polytechnic University, National University of Singapore, Chinese Academy of Sciences, Tsinghua University, and Harbin Institute of Technology are important in OTE research. China has the largest number of publications in the field of OTE, but the United States has the greatest centrality and significant influence. (2) The focus of OTE keyword clustering research is divided into four main categories: thermal environment perception, the thermal environment index, thermal environment quality, and thermal environment optimization. (3) The frontiers of OTE research have changed from focusing on environmental quality, thermal perception, numerical simulation, urban space, and thermal adaptation to thermal mitigation, energy conservation, energy consumption, and optimization strategies. Visualization research in the field of OTE helps to provide references for the direction of future research on improving climate change, human thermal comfort, urban planning, and pre-planning.

Implant-associated osteomyelitis remains a major orthopaedic problem. As neutrophil swarming to the surgical site is a critical host response to prevent infection, visualization and quantification of this dynamic behavior at the native microenvironment of infection will elucidate previously unrecognized mechanisms central to understanding the host response. We recently developed longitudinal intravital imaging of the bone marrow (LIMB) to visualize host cells and fluorescent S. aureus on a contaminated transfemoral implant in live mice, which allows for direct visualization of bacteria colonization of the implant and host cellular responses using two-photon laser scanning microscopy. To the end of rigorous and reproducible quantitative outcomes of neutrophil swarming kinetics in this model, we developed a protocol for robust segmentation, tracking, and quantifications of neutrophil dynamics adapted from Trainable Weka Segmentation and TrackMate, two readily available Fiji/ImageJ plugins. In this work, Catchup mice with tdTomato expressing neutrophils received a transfemoral pin with or without ECFP/EGFP-expressing USA300 methicillin-resistant Staphylococcus aureus (MRSA) to obtain 30-minute LIMB videos at 2-, 4-, and 6-hours post-implantation. The developed semi-automated neutrophil tracking protocol was executed independently by two users to quantify the distance, displacement, speed, velocity, and directionality of the target cells. The results revealed high inter-user reliability for all outcomes (ICC > 0.96; p > 0.05). Consistent with the established paradigm on increased neutrophil swarming during active infection, the results also demonstrated increased neutrophil speed and velocity at all measured time points, and increased displacement at later time points (6 hours) in infected versus uninfected mice (p < 0.05). Neutrophils and bacteria also exhibit directionality during migration in the infected mice. The semi-automated cell tracking protocol provides a streamlined approach to robustly identify and track individual cells across diverse experimental settings and eliminates inter-observer variability.

How to retrieve latent neurobehavioural processes from complex neurobiological signals is an important yet unresolved challenge. Here, we develop a novel approach, orthogonal-Decoding multi-Cognitive Processes (DeCoP), to reveal underlying latent neurobehavioural processing and show that its performance is superior to traditional non-orthogonal decoding in terms of both false inference and robustness. Processing value and salience information are two fundamental but mutually confounded pathways of reward reinforcement essential for decision making. During reward/punishment anticipation, we applied DeCoP to decode brain-wide responses into spatially overlapping, yet functionally independent, evaluation and readiness processes, which are modulated differentially by meso‑limbic vs nigro-striatal dopamine systems. Using DeCoP, we further demonstrated that most brain regions only encoded abstract information but not the exact input, except for dorsal anterior cingulate cortex and insula. Furthermore, we anticipate our novel analytical principle to be applied generally in decoding multiple latent neurobehavioral processes and thus advance both the design and hypothesis testing for cognitive tasks.

Dihydroxyacetone isomerization is a fundamental reaction for the production of lactic acid using different feedstocks. However, achieving excellent catalytic activity and resistance against leaching in water is challenging. Herein, we devised a Sn doped zirconium phosphate as effective heterogeneous catalyst. The incorporation of Sn could remarkably aggrandize the content of strong Lewis acid sites while retain relatively high surface areas. Gratifyingly, this catalyst exhibits enhanced activity and reusability for selective dihydroxyacetone isomerization into lactic acid with water as solvent. High lactic acid yields of 70.30 and 76.25% were achieved in water and water/acetone under optimal reaction conditions, respectively. The composition and activity of catalyst are reserved with reduced ions leaching. The excellent catalytic performance is attributed to accelerated conversion of pyruvaldehyde to lactic acid by the strong Lewis acid sites. Nuclear magnetic resonance revealed that the reaction is proceeded via a keto-enol tautomerization process.

Objective: To examine the potential effect of the probiotic strain Lactobacillus plantarum LP45 on osteoporosis and to explore the involved molecular mechanisms. Methods: A rat model of glucocorticoid-induced osteoporosis (GIO) was established, which was also orally administered with increasing doses of LP45 for 8 weeks. After the termination of the 8-week treatment, the tibia and femur bones of rats were analyzed for bone histomorphometry, bone mineral content (BMC), and bone mineral density (BMD). Femoral biomechanics were assessed. In addition, levels of osteocalcin, tartrate-resistant acid phosphatase 5 (TRAP5), osteoprotegerin (OPG), and receptor activator of nuclear factor kappa-B ligand (RANKL) in the serum and bone marrow were also measured using ELISA, Western blot, and real time-polymerase chain reaction. Results: GIO caused obvious defects in tibia and femur bone structures, in terms of tissue/bone volume, trabecular separation, trabecular thickness, and trabecular number, which could be rescued by LP45 dose dependently. The GIO-induced reductions in BMC, BMD, osteoblast surfaces per bone surface (BS), as well as elevated osteoclast surface per BS were largely restored by LP45 administration dose-dependently. LP45 also increased femoral biomechanics of GIO rats. Importantly, LP45 dose-dependently restored the changes of osteocalcin, TRAP5, OPG, and RANKL in the serum as well as bone marrow of GIO rats. Conclusion: Oral LP45 administration could significantly prevent bone defects in GIO rats, suggesting its potential as a dietary supplement with beneficial effects against osteoporosis, which might involve the RANKL/OPG signaling pathway.

Wind turbines are vulnerable to negative sequence current injection, the conventional automatic reclosing scheme for wind power outgoing lines, since we may inject negative sequence components into the system and reclose it without distinguishing the nature of the fault through rectification. Moreover, reclosing in permanent faults could induce a secondary impact on the system. To solve the above problems, an adaptive reclosing scheme for cross-line faults on double-circuit wind power outgoing lines with shunt reactors is proposed. Firstly, a new tripping strategy and a single-side partial-phase reclosing method are proposed for multiple types of outgoing line faults, while, simultaneously, phase-to-phase coupling loops are established. Secondly, the criteria of fault nature are established based on the fault phase shunt reactor current and fault phase voltage characteristics, and transient faults are rapidly and accurately distinguished from permanent ones according to the criteria. Finally, the theoretical derivation and simulation experiments are conducted on the PSCAD/EMTDC platform to demonstrate that the proposed adaptive reclosing method is applicable to avoid the injection of negative sequence currents into wind turbines. Meanwhile, the success rate of reclosing for wind power outgoing line is significantly improved and the continuity of power transmission on the wind farm(s) is ensured.

Ruthenium is required to separate from high-level liquid waste (HLLW) because Ru is a valuable resource and is negatively influential on the vitrification process of HLLW. However, the separation of Ru is very challenging due to its complicated complexation properties. In this study, the adsorption and desorption characteristics of ruthenium on a synthesized SiPyR-N3 (weak-base anion exchange resin with pyridine functional groups) composite were investigated in nitric acid and nitrite–nitric acid systems, respectively, and the adsorption mechanism was explored. The experimental results showed that SiPyR-N3 has a significantly better adsorption effect on Ru in the nitrite–nitric acid system than in the nitric acid system, with an increase in the adsorption capacity of approximately three times. The maximum adsorption capacity of Ru is 45.6 mg/g in the nitrite–nitric acid system. The SiPyR-N3 possesses good adsorption selectivity (SFRu/other metal ions is around 100) in 0.1 M NO2−–0.1 M HNO3 solution. The adsorption processes of Ru in the two different systems are fitted with the pseudo-second-order kinetic model and Langmuir model for uptake kinetics and adsorption isotherms, respectively. The results obtained from the FT-IR, XPS, and UV absorption spectrometry indicate that NO2− was involved in the adsorption process either as a complexing species with the metal ions or as free NO2− from the solution. A 0.1 M HNO3 + 1 M thiourea mixed solution shows effective desorption performance, and the desorption efficiency can reach 92% at 328 K.

Abstract Electrocatalytic urea synthesis via coupling of nitrate with CO2 is considered as a promising alternative to the industrial urea synthetic process. However, the requirement of sub‐reaction (NO3RR and CO2RR) activities for efficient urea synthesis is not clear and the related reaction mechanisms remain obscure. Here, the construction, breaking, and rebuilding of the sub‐reaction activity balance would be accompanied by the corresponding regulation in urea synthesis, and the balance of sub‐reaction activities was proven to play a vital role in efficient urea synthesis. With rational design, a urea yield rate of 610.6 mg h−1 gcat.−1 was realized on the N‐doped carbon electrocatalyst, superior to that of noble‐metal electrocatalysts. Based on the operando SR‐FTIR measurements, we proposed that urea synthesis arises from the coupling of *NO and *CO to generate the key intermediate of *OCNO. This work provides new insights and guidelines into urea synthesis from the aspect of activity balance.

The two-dimensional MoSi2N4 monolayer is an emerging semiconductor material that offers considerable promise due to its ultra-thin profile, tuneable mechanical properties, excellent optoelectronic properties and exceptional environmental stability. The van der Waals (vdW) heterostructure formed by stacking such two-dimensional monolayers has demonstrated superior performance across various domains. In this study, a vdW heterostructure combining the two-dimensional MoSi2N4 and TaS2 monolayers is examined using first-principles density functional theory. In its ground state, this van der Waals heterostructure establishes an ohmic contact with an exceptionally low potential barrier height. By modulating the vdW heterostructure with an applied electric field of -0.1 V/Å and under vertical stress, we discovered that MoSi2N4 and TaS2 can transition from an ohmic contact to a p-type Schottky with an ultra-low Schottky barrier height (SBH). Our observations may give valuable insights for designing reconfigurable, tuneable Schottky nano-devices with enhanced electronic and optical properties based on MoSi2N4/TaS2.

Electrochemical detection is widely used in biosensing fields, such as medical diagnosis and health monitoring due to its real-time response and high accuracy. Both passive and active electrodes and the corresponding readout circuits have been continuously improved over the past decades. This article summarizes the redox reaction method, state-of-the-art electrode materials, and readout circuits based on the passive three-electrode. The redox-current-based readout circuits are widely used and developed toward multichannel high precision and low power consumption. In terms of active electrodes, this article reviews the development of field-effect transistors (FETs)-based electrochemical detection and readout circuits. In the past decade, the development of organic electrochemical transistors (OECTs) has also enabled more precise electrochemical detection.

Abstract Background Osteosarcoma (OSA) is the most prevalent type of bone cancer with a high rate of metastasis. Circular RNAs (CircRNAs) play an essential role in multiple aspects of tumour biology. This study aimed to elucidate the role of circEMB in OSA. Methods circRNAs related to OSA invasion were identified via RNA sequencing and qRT-PCR. The relationship between circEMB levels and clinicopathological features of OSA was examined using the clinical specimens and data of 53 patients with OSA. Several in vivo and in vitro experiments, including intravital imaging, whole-transcriptome sequencing, transwell assay, flow cytometry, dual-luciferase reporter assay, RIP assay, RNA pull-down assay and RNA-FISH, were performed to examine the effects of circEMB on the malignant behaviour of OSA. Results A novel circRNA, named circEMB (hsa_circ_001310), was identified in this study. circEMB can promote the malignant behaviour of OSA. In vitro experiments revealed that circEMB knockdown decreased cell proliferation, inhibited tumour invasion and metastasis; increased apoptosis and resulted in G1/S phase arrest. In vivo experiments revealed that circEMB knockdown inhibited tumour growth and metastasis in xenograft-bearing mice. Mechanistically, circEMB affects the malignant behaviour of OSA by mediating EGFR as an miR-3184-5p sponge. In addition, the circEMB/miR-3184-5p/EGFR axis modulates methotrexate (MTX) resistance in OSA. Conclusions CircEMB plays a critical role in promoting cancer via the miR-3184-5p/EGFR pathway, indicating that circEMB may serve as a therapeutic target for OSA.

Introduction: Aged kidney is characterized by mitochondrial dysfunction, cellular senescence, and fibrogenesis. The activation of Wnt/β-catenin signaling plays an important role in the initiation of kidney aging. However, the inhibiting strategies have not been discovered in detail. Here, we compared the therapeutic effects of two β-catenin inhibitors, KYA1797K and ICG-001, to assess their superiority. Methods: Two-month-old male C57BL/6 mice which had undergone unilateral nephrectomy and received D-galactose (D-gal) injection were co-treated with KYA1797K or ICG-001 at 10 mg/kg/day for 4 weeks. Human proximal renal tubular cells were treated with D-gal and KYA1797K/ICG-001 to compare their effects. Results: Compared with ICG-001, which inhibits β-catenin pathway through blocking the binding of β-catenin and cAMP response element-binding protein (CREB)-binding protein (CBP), KYA1797K, a novel small molecule destabilizing β-catenin through activating Axin-GSK3β complex, possesses the superior effects on protecting against kidney aging. In D-gal-treated accelerated aging mice, KYA1797K could greatly inhibit β-catenin pathway, preserve mitochondrial homeostasis, repress cellular senescence, and retard age-related kidney fibrosis. In cultured proximal tubular cells, KYA1797K shows a better effect on inhibiting cellular senescence and could better suppress mitochondrial dysfunction and ameliorate the fibrotic changes, at the same dose as that in ICG-001. Conclusion: These results show that effectively eliminating β-catenin is a necessity to target against age-related kidney injury, suggesting the multiple transcriptional regulation of β-catenin in kidney aging besides T-cell factor/lymphoid enhancer-binding factor family of transcription factors (TCF/LEF-1).

The direct electrocatalytic synthesis of urea via C–N coupling is of great significance. The authors report a diatomic catalyst with bonded Fe–Ni pairs to improve the efficiency of electrochemical urea synthesis from nitrate and CO2.

Abstract Background The cellular dynamics in the tumour microenvironment (TME) along with non‐small cell lung cancer (NSCLC) progression remain unclear. Methods Multiplex immunofluorescence test detecting 10 immune‐related markers on 553 primary tumour (PT) samples of NSCLC was conducted and spatial information in TME was assessed by the StarDist depth learning model. The single‐cell transcriptomic atlas of PT (n = 4) and paired tumour‐draining lymph nodes (TDLNs) (n = 5 for tumour‐invaded, n = 3 for tumour‐free) microenvironment was profiled. Various bioinformatics analyses based on Gene Expression Omnibus, TCGA and Array‐Express databases were also used to validate the discoveries. Results Spatial distances of CD4+ T cells–CD38+ T cells, CD4+ T cells–neutrophils and CD38+ T cells–neutrophils prolonged and they were replaced by CD163+ macrophages in PT along with tumour progression. Neutrophils showed unique stage and location‐dependent prognostic effects. A high abundance of stromal neutrophils improved disease‐free survival in the early‐stage, whereas high intratumoural neutrophil infiltrates predicted poor prognosis in the mid‐to‐late‐stage. Significant molecular and functional reprogramming in PT and TDLN microenvironments was observed. Diverse interaction networks mediated by neutrophils were found between positive and negative TDLNs. Five phenotypically and functionally heterogeneous subtypes of tumour‐associated neutrophil (TAN) were further identified by pseudotime analysis, including TAN‐0 with antigen‐presenting function, TAN‐1 with strong expression of interferon (IFN)‐stimulated genes, the pro‐tumour TAN‐2 subcluster, the classical subset (TAN‐3) and the pro‐inflammatory subtype (TAN‐4). Loss of IFN‐stimulated signature and growing angiogenesis activity were discovered along the transitional trajectory. Eventually, a robust six neutrophil differentiation relevant genes‐based model was established, showing that low‐risk patients had longer overall survival time and may respond better to immunotherapy. Conclusions The cellular composition, spatial location, molecular and functional changes in PT and TDLN microenvironments along with NSCLC progression were deciphered, highlighting the immunoregulatory roles and evolutionary heterogeneity of TANs.

Polyurethane-cement composite are widely used in modern civil engineering, and the method of adding diluent is often used to adjust the construction process to adapt to the engineering environment. Studies have shown that the addition of diluent impacts the performance of polyurethane-cement based composite surface coatings, but there have been few reports on the influence of diluent content on the mechanical properties and microstructure of the coatings. To address this, polyurethane coatings with different diluent contents were prepared, and positron annihilation lifetime spectroscopy was used to test the microstructure of the coatings. The tensile strength and elongation at rupture were tested using a universal material testing machine, and the fracture interface morphology of each coating was observed by scanning electron microscopy. Finally, the correlation between the microstructure parameters and the mechanical properties of the coating was analyzed using grey relation theory. The results demonstrated that with the increase in diluent content, (i) the average radius of the free volume hole (R) and the free volume fraction (FV) of the coating both showed a trend of first decreasing and then increasing. The value of R was between 3.04 and 3.24 Å, and the value of FV was between 2.08 and 2.84%. (ii) The tensile strength of the coating increased first and then decreased, while the elongation at rupture decreased first and then increased. Among them, the value of tensile strength was between 3.23 and 4.02 MPa, and the value of elongation at fracture was between 49.34 and 63.04%. In addition, the free volume in polymers plays a crucial role in facilitating the migration of molecular chain segments and is closely related to the macroscopic mechanical properties of polymers. A correlation analysis showed that the R value of the coating had the greatest influence on its tensile strength, while FV showed a higher correlation with the elongation at rupture.

The Qinghai–Tibet Plateau is the main permafrost area in China. Concrete structures constructed on permafrost are affected by the early negative-temperature environment. In particular, the negative-temperature environment seriously affects the strength growth process and the frost resistance of concrete (FRC). Therefore, this study considered the influence of the gas content, water–binder ratio (w/b), age, and other factors on the strength variation law and FRC under −3 °C curing conditions. Nuclear magnetic resonance (NMR) was used to analyze the pore structure of concrete before and after freeze–thaw cycles (FTCs). The results showed that the compressive strength of the concrete (CSC) under −3 °C curing was only 57.8–86.4% of that cured under standard conditions. The CSC under −3 °C curing showed an obvious age-lag phenomenon. The FRC under −3 °C curing was much lower than that under standard curing. The porosity of the concrete under −3 °C curing was greater, with a higher percentage of harmful and multi-harmful pores than that under standard curing. The concrete properties deteriorated primarily because curing at −3 °C hindered the hydration reaction compared with standard methods. This hindrance resulted in diminished hydration development, weakening the concrete’s structural integrity. Under both curing conditions, when the gas content was between 3.2% and 3.8%, the frost resistance was the best. This is because a gas content within this range effectively enhances the internal pore structure, therefore relieving the swelling pressure caused by FTCs. Based on the freeze–thaw damage (FTD) model proposed by previous authors, a new model for the CSC under −3 °C curing reaching that of the concrete under standard curing for 28 d was established in this study. This advanced model was capable of accurately assessing the FTD of concrete structures in permafrost regions. Finally, the life expectancy of concrete in Northwest China was predicted. The life of the concrete reached 46.9 years under standard curing, while the longest life of the concrete under −3 °C curing was only 12.9 years. Therefore, attention should be paid to constructing and curing concrete structures in cold environments.

As one of the important components of Earth observation technology, land use and land cover (LULC) image classification plays an essential role. It uses remote sensing techniques to classify specific categories of ground cover as a means of analyzing and understanding the natural attributes of the Earth’s surface and the state of land use. It provides important information for applications in environmental protection, urban planning, and land resource management. However, remote sensing images are usually high-dimensional data and have limited available labeled samples, so performing the LULC classification task faces great challenges. In recent years, due to the emergence of deep learning technology, remote sensing data processing methods based on deep learning have achieved remarkable results, bringing new possibilities for the research and development of LULC classification. In this paper, we present a systematic review of deep-learning-based LULC classification, mainly covering the following five aspects: (1) introduction of the main components of five typical deep learning networks, how they work, and their unique benefits; (2) summary of two baseline datasets for LULC classification (pixel-level, patch-level) and performance metrics for evaluating different models (OA, AA, F1, and MIOU); (3) review of deep learning strategies in LULC classification studies, including convolutional neural networks (CNNs), autoencoders (AEs), generative adversarial networks (GANs), and recurrent neural networks (RNNs); (4) challenges faced by LULC classification and processing schemes under limited training samples; (5) outlooks on the future development of deep-learning-based LULC classification.

Abstract Background Relapsed childhood polymicrobial osteomyelitis associated with dermatophytosis has not been reported in the literature. Case presentation Here we report on a case of a 45-year-old man who had left tibial osteomyelitis for 29 years, accompanied by skin fungal infection of the ipsilateral heel for 20 years, and underwent a second operation due to recurrence of polymicrobial infection 6 years ago. The patient had a history of injury from a rusty object, which penetrated the anterior skin of the left tibia middle segment causing subsequent bone infection, but was asymptomatic after receiving treatments in 1983. The patient was physically normal until dermatophytosis occurred on the ipsilateral heel skin in 1998. The patient complained that the dermatophytosis was gradually getting worse, and the tibial wound site became itchy, red, and swollen. The left tibial infection resurged in May 2012, leading to the patient receiving debridement and antibiotic treatment. H&E and Gram-stained histology was performed on biopsy specimens of sequestrum and surrounding inflammatory tissue. Tissue culture and microbiology examination confirmed polymicrobial infection with Staphylococcus aureus (S. aureus) and Corynebacterium and a fungus. Additionally, the patient also received potassium permanganate for dermatophytosis when he was admitted into the hospital. Conclusions Together with longitudinal follow-up of medical history, surgical findings, histopathological and microbiology culture evidence, we conclude that boyhood tibia polymicrobial osteomyelitis with S. aureus and Corynebacterium occurred in this patient, and the fungal activation of dermatophytosis may have led to osteomyelitis relapse.

Background: Osteosarcoma is the most common primary pediatric and adolescent bone malignancy. An imbalance in copper homeostasis caused by copper ion accumulation could increase intracellular toxicity and regulate cancer cell growth. This study aimed to identify long non-coding RNAs (lncRNAs) associated with cuproptosis to predict prognosis and target drug use to improve patient survival. Methods: RNA sequencing and relevant clinical information of ninety-three osteosarcoma patients were obtained from the TARGET database. We then identified thirteen prognostic cuproptosis-related lncRNAs(CRLncs) using coexpression and univariate Cox analyses. The prognostic risk model with three CRLncs was constructed using the least absolute shrinkage and selection operator (LASSO) and multivariate Cox regression analysis. Patients were divided into low-risk and high-risk subgroups using the median risk score. The tumor microenvironment (TME) and immune status of identified subgroups were analyzed using ESTIMATE, CIBERSORT, MCP-counter, xCELL, EPIC, and ssGSEA analyses. Functional analyses were conducted to elucidate the underlying mechanisms, including GO, KEGG, GSVA, and GSEA analyses. Also, the relationships between the model, tumor immunity, and drug sensitivity were explored. Lastly, the expression level of ZNF37BP, AL353759.1, and AC005034.5 was validated in vitro. Results: We constructed a model containing three CRLncs (ZNF37BP, AL353759.1, and AC005034.5) and validated its excellent prognostic and predictive power. The AUC curves for 1-year, 3-year, and 5-year survival probabilities were 0.76, 0.84, and 0.89, respectively. Patients in the high-risk group had a shorter overall survival (OS) time than those in the low-risk. The stroma score and cancer-associated fibroblasts (CAFs) were significantly higher in the low-risk group. Immune cells such as T cells CD4 naive, T cells gamma delta, NK cells resting, dendritic cells resting, and mast cells activated were significantly upregulated in the high-risk group. Based on functional analyses, the PI3K-Akt pathway was identified as a critical metabolic pathway in osteosarcoma. Additionally, we obtained three potentially effective drugs for OS: erlotinib, MP470, and WH-4-023 targeting the PI3K-Akt pathway. The expression level of ZNF37BP was significantly elevated in OS cell lines than in normal osteoblast hFOB1.19 cells, and that of ATP7A, LIPT1, AL353759.1, and AC005034.5 were decreased considerably in OS cell lines. Conclusion: Cuproptosis-related lncRNAs are correlated with the CAFs of osteosarcoma, and this could serve as a foundation for OS survival prediction and treatment.

Abstract Deep learning techniques and deep networks have recently been extensively studied and widely applied to single image super‐resolution (SR). Among them, channel attention has garnered the most focus owing to its significant boost in the presentational power of a convolutional neural network. However, the original channel attention neglects the critical importance of the positional information, thus imposing performance limitations. Here, a novel perspective, namely, a coordinate attention mechanism, is explored to alleviate the aforementioned problem, and accordingly result in an enhanced SR performance. Specifically, a deep residual coordinate attention SR network (COSR) is proposed, which mainly incorporates the presented coordinate attention blocks into a deep nested residual structure. The coordinate attention captures the positional information by computing the average value vector from the two spatial directions, thus aggregating the features in different coordinates. The nested residual blocks pass low‐frequency information from the top to the end through the skip connection lines, allowing convolution filters to concentrate more on high‐frequency textures and edges, thereby reducing the difficulty of reconstruction. Extensive experiments demonstrate that our proposed COSR achieves a better performance and exceeds many state‐of‐the‐art SR methods in terms of both quantitative metrics and visual quality.

Abstract Background Conventional immunohistochemistry technologies were limited by the inability to simultaneously detect multiple markers and the lack of identifying spatial relationships among cells, hindering understanding of the biological processes in cancer immunology. Methods Tissue slices of primary tumours from 553 IA∼IIIB non‐small cell lung cancer (NSCLC) cases were stained by multiplex immunofluorescence (mIF) assay for 10 markers, including CD4, CD38, CD20, FOXP3, CD66b, CD8, CD68, PD‐L1, CD133 and CD163, evaluating the amounts of 26 phenotypes of cells in tumour nest and tumour stroma. StarDist depth learning model was utilised to determine the spatial location of cells based on mIF graphs. Single‐cell RNA sequencing (scRNA‐seq) on four primary NSCLC cases was conducted to investigate the putative cell interaction networks. Results Spatial proximity among CD20+ B cells, CD4+ T cells and CD38+ T cells (r2 = 0.41) was observed, whereas the distribution of regulatory T cells was associated with decreased infiltration levels of CD20+ B cells and CD38+ T cells (r2 = −0.45). Univariate Cox analyses identified closer proximity between CD8+ T cells predicted longer disease‐free survival (DFS). In contrast, closer proximity between CD133+ cancer stem cells (CSCs), longer distances between CD4+ T cells and CD20+ B cells, CD4+ T cells and neutrophils, and CD20+ B cells and neutrophils were correlated with dismal DFS. Data from scRNA‐seq further showed that spatially adjacent N1‐like neutrophils could boost the proliferation and activation of T and B lymphocytes, whereas spatially neighbouring M2‐like macrophages showed negative effects. An immune‐related risk score (IRRS) system aggregating robust quantitative and spatial prognosticators showed that high‐IRRS patients had significantly worse DFS than low‐IRRS ones (HR 2.72, 95% CI 1.87–3.94, p

Investigations of the hot spring water and gas in the volcanic region are involved in assessing geothermal resources and understanding groundwater circulation, volcano, and earthquake activities. The origins of water and gas of the hot springs, lakes, rivers, and rain in the Arxan volcanic region (AVR), northeastern (NE) China, were investigated by conducting a field survey and geochemical analysis. The low electrical conductivity (40–835 μS/cm) and low total dissolved solids (TDS, 23.83–540.00 mg/L) of the water samples indicate that they are fresh water. δ18O and δD values of the water samples range from −4.1% to −16.0% and from −61.3% to −119.9%, respectively. Enrichment of heavy isotopes in the rainwater and the crater lake waters was caused by evaporation. The component H2O of the water samples predominantly originated from the meteoric water, with less than 1 vol% contributed by deep-earth fluids. Ions in the rain sample were predominantly derived from sea salt and continental aerosol. Ions in the surface water samples had multiple origins (mineral dissolution, atmospheric, and anthropogenic sources). While the ions in the hot spring water were predominantly derived from both the dissolution of rocks and deep-earth fluids, the latter contributed 73%–87% of Cl− and 86%–99% of Na+ to the hot spring waters. Gases from the hot springs were composed of more than 95% N2 and less than 5% O2 and Ar, with 3He/4He ratios of 0.14–1.17 RA (RA=1.4×10−6). Excess N2, Ar, He, and CO2 of the hot springs were mainly derived from both the crust and upper mantle. About 3%–23% of the total He in the bubbling gases from the crater lake waters and hot springs is derived from the mantle, implying a supplement of heat energy from the mantle to the geothermal systems. Significantly, about 12% of the He dissolved in the Budonghe water is derived from the mantle, indicating that plenty of mantle-derived heat transported by deep-earth fluids keeps the river water from freezing. Our results indicate that Cl and Na ions and 3He/4He ratio are the feasible geochemical indicators for source partitioning of geothermal fluids.

The right aortic arch (RAA) is a rare congenital vascular variant disease. We reported a case of subclavian steal syndrome associated with RAA. The primary clinical symptoms were vertigo and ischemic symptoms of the left upper extremity. We diagnosed the condition using aortic computed tomography angiography and digital subtraction angiography. The patient underwent carotid-subclavian bypass surgery.

Small-diameter vascular grafts (diameter

Selective cleavage of C-C bonds is very important in organic chemistry, but remains challenging because of their inert chemical nature. Here, the authors report that Zn2+ coordinated with N species on N-doped carbon catalysts can catalyze the aerobic oxidative cleavage and esterification of C(CO)-C bonds with high efficiency and activity.

Introduction The histopathology grading system is the gold standard post-operative method to evaluate cartilage degeneration in knee osteoarthritis (OA). Magnetic resonance imaging (MRI) T1 rho/T2 mapping imaging can be used for preoperative detection. An association between histopathology and T1 rho/T2 mapping relaxation times was suggested in previous research. However, the cutoff point was not determined among different histopathology grades. Our study aimed to determine the cutoff point of T1 rho/T2 mapping. Material and methods T1 rho/T2 mapping images were acquired from 80 samples before total knee replacements. Then the histopathology grading system was applied. Results The mean T1 rho/T2 mapping relaxation times of 80 samples were 39.17 ms and 37.98 ms respectively. Significant differences were found in T1 rho/T2 mapping values between early-stage and advanced OA (p < 0.001). The cutoff point for T1 rho was 33 ms with a sensitivity of 94.12 (95% CI: 80–99.3) and a specificity of 91.30 (95% CI: 79.2–97.6). The cutoff point for T2 mapping was suggested as 35.04 ms with a sensitivity of 88.24 (95% CI: 72.5–96.7) and specificity of 97.83 (95% CI: 88.5–99.9). After bootstrap simulation, the 95% CI of the T1 rho/T2 mapping cutoff point was estimated as 29.36 to 36.32 ms and 34.8 to 35.04 ms respectively. The area under the PR curve of T1 rho/T2 mapping was 0.972 (95% CI: 0.925–0.992) and 0.949 (95% CI: 0.877–0.989) respectively. Conclusions The cutoff point of T1 rho relaxation times, which was suggested as 33 ms, could be used to distinguish early-stage and advanced OA.

Ciliopathies are a class of genetic diseases resulting in cilia dysfunction in multiple organ systems, including the olfactory system. Currently, there are no available curative treatments for olfactory dysfunction and other symptoms in ciliopathies. The loss or shortening of olfactory cilia, as seen in multiple mouse models of the ciliopathy Bardet–Biedl syndrome (BBS), results in olfactory dysfunction. However, the underlying mechanism of the olfactory cilia reduction is unknown, thus limiting the development of therapeutic approaches for BBS and other ciliopathies. Here, we demonstrated that phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2], a phosphoinositide typically excluded from olfactory cilia, aberrantly redistributed into the residual cilia of BBS mouse models, which caused F-actin ciliary infiltration. Importantly, PI(4,5)P2 and F-actin were necessary for olfactory cilia shortening. Using a gene therapeutic approach, the hydrolyzation of PI(4,5)P2 by overexpression of inositol polyphosphate-5-phosphatase E (INPP5E) restored cilia length and rescued odor detection and odor perception in BBS. Together, our data indicate that PI(4,5)P2/F-actin–dependent cilia disassembly is a common mechanism contributing to the loss of olfactory cilia in BBS and provide valuable pan-therapeutic intervention targets for the treatment of ciliopathies.

BackgroundsPulmonary arterial hypertension (PAH) is characterized by progressive pulmonary vascular functional and structural changes, resulting in increased pulmonary vascular resistance and eventually right heart failure and death. Congenital Left-to-Right shunts (LTRS) is one type of congenital heart disease (CHD) and PAH associated with the congenital Left-to-Right shunt (PAH-LTRS) is a severe disease in children. However, changes in the lung microbiome and their potential impact on PAH-LTRS have not been not fully studied. We hypothesized that lung microbiota and their derived metabolites have been disturbed in children with PAH-LTRS, which might contribute to the progression and outcomes of PAH-LTRS.MethodsIn this study, 68 age- and sex-matched children of three different groups (patients with PAH-LTRS cohort, patients with LTRS but have no pathologic features of PAH cohort, and healthy reference cohort) were enrolled in the current study. Bronchoalveolar lavage fluid samples from these participants were conducted for multi-omics analysis, including 16S rRNA sequencing and metabolomic profiling. Data progressing and integration analysis were performed to identify pulmonary microbial and metabolic characteristics of PAH-LTRS in children.ResultsWe found that microbial community density was not significantly altered in PAH-LTRS based on α-diversity analysis. Microbial composition analysis indicated phylum of Bacteroidetes was that less abundant while Lactobacillus, Alicycliphilus, and Parapusillimonas were significantly altered and might contribute to PAH in children with LTRS. Moreover, metabolome profiling data showed that metabolites involved in Purine metabolism, Glycerophospholipid metabolism, Galactose metabolism, and Pyrimidine metabolism were also significantly disturbed in the PAH-LTRS cohort. Correlation analysis between microbes and metabolites indicated that alterations in the microbial composition from the lung microbiota could eventually result in the disturbance in certain metabolites, and might finally contribute to the pathology of PAH-LTRS.ConclusionLung microbial density was not significantly altered in patients with PAH-LTRS. Composition analysis results showed that the relative microbiome abundance was different between groups. Metabolome profiling and correlation analysis with microbiota showed that metabolome also altered in children with PAH-LTRS. This study indicated that pulmonary microbes and metabolites disturbed in PAH-LTRS could be potentially effective biomarkers and provides valuable perspectives on clinical diagnosis, treatment, and prognosis of pediatric PAH-LTRS.

Managing the power transients with both high efficiency and thermal management constraints is a difficult task in the solid oxide fuel cell (SOFC) hybrid direct-current (DC) microgrids. This article proposed a SOFC-based DC microgrid, which consists of the SOFC stand-alone system, DC microgrid network, and DC/DC boost converter, along with the associated DC/DC load. The control and optimization strategy of the SOFC-based DC microgrids has been designed, including the thermal and electrical characteristics analysis. First, the voltage and current regulator based on the proportional–integral (PI) is designed, which can maintain the voltage stability of the proposed SOFC system. In addition, the optimal regulator based on the optimal operating points (OOPs) is designed, which can realize high efficiency and steady-state thermal safety of the proposed SOFC system. Finally, the main performance, including the SOFC stack electrical characteristics verification, SOFC stand-alone system electrical and thermal response, load-tracking characteristics, and system efficiency is observed and discussed in the proposed control and optimization strategy. Experimental results verify the correctness of the theoretical analysis and the effectiveness of the proposed optimization and control strategy.