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Abstract Alcoholysis of poly(ethylene terephthalate) (PET) waste to produce monomers, including methanolysis to yield dimethyl terephthalate (DMT) and glycolysis to generate bis-2-hydroxyethyl terephthalate (BHET), is a promising strategy in PET waste management. Here, we introduce an efficient PET-alcoholysis approach utilizing an oxygen-vacancy (V o)-rich catalyst under air, achieving space time yield (STY) of 505.2 gDMT·gcat −1·h−1 and 957.1 gBHET·gcat −1·h−1, these results represent 51-fold and 28-fold performance enhancements compared to reactions conducted under N2. In situ spectroscopy, in combination with density functional theory calculations, elucidates the reaction pathways of PET depolymerization. The process involves O2-assisted activation of CH3OH to form CH3OH* and OOH* species at V o-Zn2+–O–Fe3+ sites, highlighting the critical role of V o-Zn2+–O–Fe3+ sites in ester bond activation and C–O bond cleavage. Moreover, a life cycle assessment demonstrates the viability of our approach in closed-loop recycling, achieving 56.0% energy savings and 44.5% reduction in greenhouse-gas emissions. Notably, utilizing PET textile scrap further leads to 58.4% reduction in initial total operating costs. This research offers a sustainable solution to the challenge of PET waste accumulation.

AIM: To compare the efficacy of pars plana vitrectomy (PPV) combined with internal limiting membrane (ILM) and silicone oil or sterile air tamponade for the treatment of myopic foveoschisis (MF) in highly myopic eyes. METHODS: This retrospective study included 48 myopic eyes of 40 patients with MF and axial lengths (ALs) ranging from 26-32 mm treated between January 2020 and January 2022. All patients were underwent PPV combined with ILM peeling followed by sterile air or silicone oil tamponade and followed up at least 12mo. Based on the features on spectral-domain optical coherence tomography (SD-OCT), the eyes were divided into the MF-only group (Group A, n=15 eyes), MF with central foveal detachment group (Group B, n=20 eyes), and MF with lamellar macular hole group (Group C, n=13 eyes). According to AL, eyes were further divided into three groups: Group D (26.01-28.00 mm, n=12 eyes), Group E (28.01-30.00 mm, n=26 eyes), and Group F (30.01-32.00 mm, n=10 eyes). The best-corrected visual acuity (BCVA), central foveal thickness (CFT), and complications were recorded. RESULTS: The patients included 16 males and 24 females with the mean age of 56±9.82y. The BCVA and CFT improved in all groups after surgery (P0.05). The intergroup differences of BCVA and CFT postoperatively were statistically significant in Group D, E, and F. Twenty eyes were injected with sterile air, and 28 eyes were injected with silicone oil for tamponade based on the AL. However, there was no statistically significant difference among Groups D, E, and F in terms of the results of sterile air or silicone oil tamponade. The mean recovery time was 5.9mo for MF patients subjected to silicone oil tamponade and 7.7mo for patients subjected to sterile air tamponade, and the difference was not statistically significant. CONCLUSION: PPV and ILM peeling combined with silicone oil or sterile air tamponade can achieve good results for MF in highly myopic eyes with ALs≤32 mm.

Abstract We aim to develop machine learning (ML) models for predicting the complexity and mortality of polytrauma patients using clinical features, including physician diagnoses and physiological data. We conducted a retrospective analysis of a cohort comprising 756 polytrauma patients admitted to the intensive care unit (ICU) at Pizhou People’s Hospital Trauma Center, Jiangsu, China between 2020 and 2022. Clinical parameters encompassed demographics, vital signs, laboratory values, clinical scores and physician diagnoses. The two primary outcomes considered were mortality and complexity. We developed ML models to predict polytrauma mortality or complexity using four ML algorithms, including Support Vector Machine (SVM), Random Forest (RF), Artificial Neural Network (ANN) and eXtreme Gradient Boosting (XGBoost). We assessed the models’ performance and compared the optimal ML model against three existing trauma evaluation scores, including Injury Severity Score (ISS), Trauma Index (TI) and Glasgow Coma Scale (GCS). In addition, we identified several important clinical predictors that made contributions to the prognostic models. The XGBoost-based polytrauma mortality prediction model demonstrated a predictive ability with an accuracy of 90% and an F-score of 88%, outperforming SVM, RF and ANN models. In comparison to conventional scoring systems, the XGBoost model had substantial improvements in predicting the mortality of polytrauma patients. External validation yielded strong stability and generalization with an accuracy of up to 91% and an AUC of 82%. To predict polytrauma complexity, the XGBoost model maintained its performance over other models and scoring systems with good calibration and discrimination abilities. Feature importance analysis highlighted several clinical predictors of polytrauma complexity and mortality, such as Intracranial hematoma (ICH). Leveraging ML algorithms in polytrauma care can enhance the prognostic estimation of polytrauma patients. This approach may have potential value in the management of polytrauma patients.

Coordinated contraction of skeletal muscles relies on selective connections between the muscles and multiple classes of the spinal motoneurons. However, current research on the spatial location of the spinal motoneurons innervating different muscles is limited. In this study, we investigated the spatial distribution and relative position of different motoneurons that control the deep muscles of the mouse hindlimbs, which were innervated by the obturator nerve, femoral nerve, inferior gluteal nerve, deep peroneal nerve, and tibial nerve. Locations were visualized by combining a multiplex retrograde tracking technique compatible with three-dimensional imaging of solvent-cleared organs (3DISCO) and 3-D imaging technology based on lightsheet fluorescence microscopy (LSFM). Additionally, we propose the hypothesis that “messenger zones” exist as interlaced areas between the motoneuron pools that dominate the synergistic or antagonist muscle groups. We hypothesize that these interlaced neurons may participate in muscle coordination as messenger neurons. Analysis revealed the precise mutual positional relationships among the many motoneurons that innervate different deep muscles of the mouse. Not only do these findings update and supplement our knowledge regarding the overall spatial layout of spinal motoneurons that control mouse limb muscles, but they also provide insights into the mechanisms through which muscle activity is coordinated and the architecture of motor circuits.

Abstract Sepsis is a life‐threatening organ dysfunction syndrome caused by the host's dysregulated response to infection. The leading causes of death in critically ill patients are sepsis‐associated encephalopathy (SAE), respiratory dysfunction, circulatory dysfunction, and other multi‐organ dysfunctions. SAE is among the most common serious complications of sepsis and is associated with a poor prognosis and long‐term cognitive dysfunction. Its clinical manifestations vary, and there are still no unified diagnostic criteria. The incidence of SAE varies from 9% to 71% in critically ill patients due to therapeutic interventions such as sedation, mechanical ventilation, and muscle relaxants. Advances in medical technology have significantly increased the survival rate of patients with sepsis, but up to 21% now experience long‐term sequelae or cognitive impairment. The lack of specific early diagnostic and treatment methods leads to increased SAE‐associated mortality and complications in patients, which also impose heavy economic burdens. This article reviews the pathogenesis and diagnostic methods of SAE and progress in its treatment, aiming to reduce the mortality and hospitalization lengths of patients with SAE and improve their survival rate and quality of life through early detection, diagnosis, and effective treatment.

The stability of reservoir slopes is often greatly influenced by seasonal rainfall and periodic water level fluctuation. To reveal the spatiotemporal characteristics of displacement and the mechanism of the active slopes, it is of great significance to identify active slopes on reservoir banks and extract periodic displacements. The wavelet transform method based on least squares decomposition has been used to extract periodic displacements of reservoir slopes, which only divides displacements into two components, neglecting errors such as random terms. This paper proposes a method that combines Independent Component Analysis (ICA) and wavelet transform to investigate the temporal relationship between periodic displacements and water level fluctuations. Taking the Maoergai Hydropower Station in Heishui County as example, based on ascending and descending SAR images acquired from 2018 to 2020, a total of 21 active slopes were detected. The time series InSAR results were decomposed by ICA. Through separate analysis and validation on typical slopes, it was demonstrated that the obtained periodic displacements are highly consistent with the water level fluctuations, and displacement changes lag behind water level fluctuations. Cross-validation was performed and proved the stability and reliability of the time lag (about 80–88 days derived from ascending and descending observation) results in this paper. This study improves the accuracy and stability of the periodic displacement extraction and provides technical support for understanding the relationship between the water level fluctuations and the slope displacements.

BackgroundThe efficacy and safety of deep transcranial magnetic stimulation (dTMS) as an intervention for schizophrenia remain unclear. This systematic review examined the efficacy and safety of dTMS for schizophrenia.MethodsA systematic search of Chinese (WanFang and Chinese Journal Net) and English databases (PubMed, EMBASE, PsycINFO, and Cochrane Library) were conducted.ResultsThree randomized clinical trials (RCTs) comprising 80 patients were included in the analyses. Active dTMS was comparable to the sham treatment in improving total psychopathology, positive symptoms, negative symptoms, and auditory hallucinations measured by the Positive and Negative Syndrome Scale (PANSS), the Scale for the Assessment of Positive Symptoms (SAPS), the Scale for the Assessment of Negative Symptoms (SANS), and the Auditory Hallucinations Rating Scale (AHRS), respectively. Only one RCT reported the effects on neurocognitive function measured by the Cambridge Neuropsychological Test Automated Battery (CANTAB), suggesting that dTMS may only improve one Stockings of Cambridge measure (i.e., subsequent times for five move problems). All three studies reported overall discontinuation rates, which ranged from 16.7% to 44.4%. Adverse events were reported in only one RCT, the most common being tingling/twitching (30.0%, 3/10), head/facial discomfort (30.0%, 3/10), and back pain (20.0%, 2/10).ConclusionThis systematic review suggests that dTMS does not reduce psychotic symptoms in schizophrenia, but it shows potential for improving executive functions. Future RCTs with larger sample sizes focusing on the effects of dTMS on psychotic symptoms and neurocognitive function in schizophrenia are warranted to further explore these findings.

Acute lymphoblastic leukemia (ALL) represents a malignancy involving early-stage differentiated lymphoid cells that invade the bone marrow, blood, and extramedullary sites. First-line treatment spans 2–3 years with induction, consolidation, intensification, and long-term maintenance phases. Relapsed/refractory (R/R) ALL typically carries an adverse prognosis, and there is currently no standard of care for this disease. Here, we present a case of R/R ALL that responded effectively to liposomal mitoxantrone-based multidrug chemotherapy, resulting in a rapid complete response after 35 days of therapy. Subsequently, the patient was successfully treated with allo-HSCT. At 5 months follow-up, the patient was alive and leukemia-free. Additionally, no severe adverse events were recorded during liposomal mitoxantrone treatment or hospitalization for allo-HSCT. Given the encouraging efficacy and the manageable adverse events observed in our case, liposomal mitoxantrone-based multidrug chemotherapy should be further explored as a bridge to allo-HSCT in patients with R/R ALL.

Hyperuricemia is an independent risk factor for chronic kidney disease and contributes to renal fibrosis. This study aims to investigate the effect of Src family kinase (SFK) inhibition on the development of hyperuricemic nephropathy (HN) and the mechanisms involved. In a rat model of HN, feeding rats a mixture of adenine and potassium oxonate increased Src phosphorylation, severe glomerular sclerosis, and renal interstitial fibrosis, accompanied by renal dysfunction and increased urine microalbumin excretion. Administration of PP1, a highly selective SFK inhibitor, prevented renal dysfunction, reduced urine microalbumin, and inhibited activation of renal interstitial fibroblasts and expression of extracellular proteins. PP1 treatment also inhibited hyperuricemia-induced activation of the TGF-β1/Smad3, STAT3, ERK1/2, and NF-κB signaling pathways and expression of multiple profibrogenic cytokines/chemokines in the kidney. Furthermore, PP1 treatment significantly reduced serum uric acid levels and xanthine oxidase activity. Thus, blocking Src can attenuate development of HN via a mechanism associated with the suppression of TGF-β1 signaling, inflammation, and uric acid production. The results suggest that Src inhibition might be a promising therapeutic strategy for HN.

The chemical recycling of polyolefin presents a considerable challenge, especially as upcycling methods struggle with the reality that plastic wastes typically consist of mixtures of polyethylene (PE), polystyrene (PS), and polypropylene (PP). We report a catalytic aerobic oxidative approach for polyolefins upcycling with the corresponding carboxylic acids as the product. This method encompasses three key innovations. First, it operates under atmospheric pressure and mild conditions, using O2 or air as the oxidant. Second, it is compatible with high-density polyethylene, low-density polyethylene, PS, PP, and their blends. Third, it uses an economical and recoverable metal catalyst. It has been demonstrated that this approach can efficiently degrade mixed wastes of plastic bags, bottles, masks, and foam boxes.

On August 8, 2017, a magnitude 7.0 earthquake struck Jiuzhaigou County in Sichuan Province, triggering numerous coseismic landslides. The prompt identification of these landslides is imperative for emergency rescue efforts and post-earthquake hazard assessments. Optical satellite and unmanned aerial vehicle (UAV) images are often obstructed by cloud cover and fog following earthquakes. In contrast, polarimetric synthetic aperture radar (PolSAR), unaffected by adverse weather conditions, emerges as an indispensable tool. However, the utilization of spaceborne single-temporal SAR for mapping the inventory of coseismic landslides is infrequent and encounters constraints due to several limitations. In this study, we analyzed the amplitude feature and polarimetric decomposition of multiple ground categories in a full PolSAR image, and proposed an automated method to accurately identify coseismic landslides using a single-temporal full PolSAR image. The coseismic landslide inventory following the Jiuzhaigou Earthquake was mapped and validated using high-resolution UAV images. Detailed analysis was conducted to identify error sources leading to omissions and false positives. Additionally, we evaluated various machine learning models to compare their performance with our proposed method. Finally, we conducted a comprehensive discussion on the strengths and weaknesses of different data types (PolSAR, optical satellite, and UAV) for coseismic landslide identification. Our results indicate that the proposed PolSAR-based method achieves high accuracy in coseismic landslide inventory mapping, offering an effective solution for timely post-earthquake emergency responses in complex environments and all weather conditions in the future.

Abstract Background Sepsis is a life‐threatening organ dysfunction caused by a dysregulated host response to infection and progressive immunosuppression with high mortality. HLA‐DR, CD64, and PD‐1 were assumed to be useful biomarkers for sepsis prediction. However, the ability of a combination of these biomarkers has not been clarified. Methods An observational case‐control study was conducted that included 30 sepsis patients, 30 critically ill patients without sepsis admitted to the intensive care unit (ICU), and 32 healthy individuals. The levels of HLA‐DR, CD64, and PD‐1 expression in peripheral blood immune cells and subsets was assayed on Days 1, 3, and 5, and the clinical information of patients was collected. We compared these biomarkers between groups and evaluated the predictive validity of single and combined biomarkers on sepsis mortality. Results The results indicate that PD‐1 expression on CD4−CD8−T (PD‐1+CD4−CD8−T) (19.19% ± 10.78% vs. 9.88% ± 1.79%, p = .004) cells and neutrophil CD64 index (nCD64 index) (9.15 ± 5.46 vs. 5.33 ± 2.34, p = .001) of sepsis patients were significantly increased, and HLA‐DR expression on monocytes (mHLA‐DR+) was significantly reduced (13.26% ± 8.06% vs. 30.17% ± 21.42%, p = 2.54 × 10−4) compared with nonsepsis critically ill patients on the first day. Importantly, the expression of PD‐1+CD4−CD8−T (OR = 0.622, 95% CI = 0.423–0.916, p = .016) and mHLA‐DR+ (OR = 1.146, 95% CI = 1.014–1.295, p = .029) were significantly associated with sepsis mortality. For sepsis diagnosis, the mHLA‐DR+, PD‐1+CD4−CD8−T, and nCD64 index showed the moderate individual performance, and combinations of the three biomarkers achieved greater diagnostic value (AUC = 0.899, 95% CI = 0.792–0.962). When adding PCT into the combined model, the AUC increased to 0.936 (95% CI = 0.840–0.983). For sepsis mortality, combinations of PD‐1+CD4−CD8−T and mHLA‐DR+, have a good ability to predict the prognosis of sepsis patients, with an AUC = 0.921 (95% CI = 0.762–0.987). Conclusion These findings indicate that the combinations of HLA‐DR, CD64, and PD‐1 outperformed each of the single indicator in diagnosis and predicting prognosis of sepsis.

Osteoarthritis (OA) is a highly prevalent age-related musculoskeletal disorder that typically results in chronic pain and disability. OA is a multifactorial disease, with increased oxidative stress, dysregulated inflammatory response, and impaired matrix metabolism contributing to its onset and progression. The neurohormone melatonin, primarily synthesized by the pineal gland, has emerged as a promising therapeutic agent for OA due to its potential to alleviate inflammation, oxidative stress, and chondrocyte death with minimal adverse effects. The present review provides a comprehensive summary of the current understanding regarding melatonin as a promising pharmaceutical agent for the treatment of OA, along with an exploration of various delivery systems that can be utilized for melatonin administration. These findings may provide novel therapeutic strategies and targets for inhibiting the advancement of OA.

Vascular endothelial growth factor and its mimic peptide KLTWQELYQLKYKGI (QK) are widely used as the most potent angiogenic factors for the treatment of multiple ischemic diseases. However, conventional topical drug delivery often results in a burst release of the drug, leading to transient retention (inefficacy) and undesirable diffusion (toxicity) in vivo. Therefore, a drug delivery system that responds to changes in the microenvironment of tissue regeneration and controls vascular endothelial growth factor release is crucial to improve the treatment of ischemic stroke. Matrix metalloproteinase-2 (MMP-2) is gradually upregulated after cerebral ischemia. Herein, vascular endothelial growth factor mimic peptide QK was self-assembled with MMP-2-cleaved peptide PLGLAG (TIMP) and customizable peptide amphiphilic (PA) molecules to construct nanofiber hydrogel PA-TIMP-QK. PA-TIMP-QK was found to control the delivery of QK by MMP-2 upregulation after cerebral ischemia/reperfusion and had a similar biological activity with vascular endothelial growth factor in vitro. The results indicated that PA-TIMP-QK promoted neuronal survival, restored local blood circulation, reduced blood-brain barrier permeability, and restored motor function. These findings suggest that the self-assembling nanofiber hydrogel PA-TIMP-QK may provide an intelligent drug delivery system that responds to the microenvironment and promotes regeneration and repair after cerebral ischemia/reperfusion injury.

Peripheral nerve injury can lead to progressive muscle atrophy and poor motor function recovery, which is a difficult point of treatment, and the mechanism needs to be further explored. In previous studies, we found that miR-142a-3p was significantly upregulated and persistently highly expressed in denervated mouse skeletal muscle. Here, we show that overexpression of miR-142a-3p inhibited the growth and differentiation of C2C12 myoblast, while knockdown of miR-142a-3p had a promoting effect. In vitro, knockdown of miR-142a-3p in denervated mouse skeletal muscle effectively increased proliferating muscle satellite cells and ameliorated muscle atrophy. Mechanistically, the myoregulator Mef2a was proved to be an important downstream target of miR-142a-3p, and miR-142a-3p regulates skeletal muscle differentiation and regeneration by inhibiting the expression of Mef2a. The co-knockdown of Mef2a and miR-142a-3p effectively alleviated or offset the biological effects of miR-142a-3p knockdown. In conclusion, our data revealed that miR-142a-3p regulates neurogenic skeletal muscle atrophy by targeting Mef2a.

Abstract The carbon reduction effect of bio-based levulinic acid chemicals is a matter of concern. This work reports the life cycle assessment of methyl levulinate based on local biomass refineries in China. The final LCA results showed that the entire life cycle of methyl levulinate could reduce by approximately 24% of carbon emissions compared with fossil diesel of equal quality. To address the lack of effective uncertainty analysis in current LCA research on levulinic acid chemicals, this study conducted a comprehensive and detailed assessment of inventory data and utilized Taylor series expansion to obtain uncertainty of the LCA results. When connected to a localized background database, the LCA results showed high credibility. According to the sensitivity analysis and Aspen optimization results, further technical improvement schemes are proposed, including improving thermal efficiency, use of clean electricity, and use of clean methanol. Prospective analysis shows that combined implementation of the above strategies can further reduce the existing carbon emissions by more than half. Graphical Abstract

Abstract Sepsis is the uncontrolled reaction of the body to infection-induced inflammation, which results in life-threatening multiple-organ dysfunction (MODS). Although the research on sepsis has advanced significantly in recent years, its pathophysiology remains entirely unknown. Ferroptosis is a new-fashioned type of programmed cell death that may have an impact on sepsis development. However, the precise mechanism still needs to be explored. In this paper, Four pediatric sepsis datasets [training datasets (GSE26378 and GSE26440) and validation datasets (GSE11755 and GSE11281)] were chosen through the GEO (Gene Expression Omnibus) database, and 63 differentially expressions of ferroptosis-relation-genes (DE-FRGs) were eventually discovered using bioinformatics investigation. Functional annotation was performed using GO and KEGG pathway enrichment analysis. Then, four Core-FRGs (FTH1, GPX4, ACSL1, and ACSL6) were extracted after the construction of the protein–protein interaction (PPI) network and the research of the MCODE module. Consequently, Hub-FRG (GPX4) was found using the validation datasets, and correlation exploration of immunity populations (neutrophils, r = − 0.52; CD8 T-cells, r = 0.43) and immunity checkpoints (CD274, r = − 0.42) was implemented. The usefulness of GPX4 as a marker in sepsis was assessed in a mouse model of sepsis. The findings demonstrate that GPX4 is a crucial biomarker and a new latent immunotherapy target for the prediction and therapy of pediatric sepsis.

The Baihetan reservoir region is characterized by complex geomorphology, significant altitude differences, and rugged terrain. Geological hazards in such areas are often characterized by high concealment, wide distribution, and difficulty in field investigation. Traditional identification techniques are unable to detect and monitor geological hazards on a large scale with high efficiency and accuracy. In recent decades, interferometric synthetic aperture radar (InSAR) techniques, such as small baseline subset InSAR (SBAS-InSAR), have been widely applied to landslide identification. However, due to factors such as vegetation and the degree of landslide deformation, single-band synthetic aperture radar (SAR) still has certain limitations in detecting landslides. In this study, SBAS-InSAR was conducted based on ALOS-2 and Sentinel-1 ascending-descending images covering the Baihetan reservoir region. Deformation identification results were utilized to conduct a statistical analysis of the SAR detection performance and landslide characteristics, and the effect of vegetation on the detection effectiveness of different SAR bands was discussed. The study revealed that when surface vegetation coverage reaches a high degree, the percentage of areas with coverage greater than 0.6 is greater than 95%, the SAR coherence is mainly affected by vegetation thickness; the comparison of the difference change in the average coherence of the C/L bands among the four vegetation types shows that the ratio of the average coherence of the L-bands to the C-bands increases by a factor of three with the increase in thickness and the transition from crops to shrubs and trees. The results showed that the L-band has better detectability than the C-band in alpine-canyon terrain with vegetation coverage and complex vegetation composition. However, considering the high temporal resolution and accessibility of Sentinel-1 SAR data, it is still the main data choice for wide-area identification of landslides in the reservoir area, while other satellite-borne SAR data with different wavelengths and resolutions, such as ALOS, can be used to assist in the identification and monitoring of landslide hazards with significant magnitude of deformations and dense vegetation coverage. Therefore, the combined utilization of multi-band SAR data has the potential to enhance the dependability of landslide identification and monitoring, resulting in more accurate detection results.

Abstract To reduce environmental pollution and reliance on fossil resources, polyethylene terephthalate as the most consumed synthetic polyester needs to be recycled effectively. However, the existing recycling methods cannot process colored or blended polyethylene terephthalate materials for upcycling. Here we report a new efficient method for acetolysis of waste polyethylene terephthalate into terephthalic acid and ethylene glycol diacetate in acetic acid. Since acetic acid can dissolve or decompose other components such as dyes, additives, blends, etc., Terephthalic acid can be crystallized out in a high-purity form. In addition, Ethylene glycol diacetate can be hydrolyzed to ethylene glycol or directly polymerized with terephthalic acid to form polyethylene terephthalate, completing the closed-loop recycling. Life cycle assessment shows that, compared with the existing commercialized chemical recycling methods, acetolysis offers a low-carbon pathway to achieve the full upcycling of waste polyethylene terephthalate.

The existence of Himalayan long-eared bats, Plecotus homochrous (Chiroptera, Vespertilionidae), in China has not been previously confirmed. In this study, four bats captured with harp traps from two sites in the Maoershan National Nature Reserve in Guangxi, China were investigated. These bats have long, wide auricles, each with a prominent tragus. The length of each auricle is about the same as that of a forearm. Hairs on the ventral fur have a dark base with mixed grey and yellowish tips; those on the dorsal fur also have a dark base and are bicolored with brown tips. The thumbs are very short. A concavity is present in the front of the dorsal side of the cranium. Based on morphological characteristics and phylogeny using Cyt b gene sequences, these bats were identified as P. homochrous, thus confirming the existence of Himalayan long-eared bats in China.

Reservoir water fluctuation in supply and storage cycle have strong triggering effects on landslides on both sides of reservoir banks. Early identification of reservoir landslides and revealing the relationship between slope stability and the triggering factors including reservoir level and rainfall, are of great significance in further protecting nearby residents’ lives and properties. In this paper, based on the small baseline subset time series method (SBAS-InSAR), the potential landslides with active displacements in the river bank of Maoergai hydropower station in Heishui County from 2018 to 2020 were monitored with Sentinel-1 data. As a result, a total of 20 unstable slopes were detected. Subsequently, it was found through a gray correlation analysis that the fluctuation of the reservoir water level is the main triggering factor for the displacement on unstable slopes. This paper applied wavelet tools to quantify the time lag between slope stability and reservoir water fluctuation, revealing that the displacement exhibits a seasonal trend, whose high-frequency signal displacement has an interannual period (1 year). Based on the Cross Wavelet Transform (XWT) analysis, under the interannual scale of one year, the reservoir water fluctuation and nonlinear displacement show a clear common power in wavelet. Additionally, a time lag of 65–120 days between slope stability and reservoir water fluctuations has been found, indicating that the non-linear displacements were behind the water level changes. Among the factors affecting the time lag, the elevation of the points and their distance to the bank shore show Pearson’s correlation coefficients of 0.69 and 0.70, respectively. The observed time lag and correlations could be related to the gradual saturation/drainage processes of the slope and the drainage path. This paper demonstrates the technical support to quantitatively reveal the time lag between slope stability and reservoir water fluctuation by InSAR and wavelet tools, providing strong support for the analysis of the mechanisms of landslides in Maoergai reservoir area.

AIM: To evaluate the long-term results of patients with chronic uveitis-induced cataract by phacoemulsification with IOL implantation and intravitreal injection of dexamethasone (DEX) intravitreal implant (Ozurdex). METHODS: The study included 32 eyes of 26 patients treated with DEX implant due to chronic uveitis-induced cataract and followed up for at least a year. Best-corrected visual acuity (BCVA), intraocular pressure (IOP), anterior chamber reaction, central macular thickness (CMT), intraoperative and postoperative complications and uveitis recurrence were analyzed retrospectively. RESULTS: A successful surgery was performed in all patients. The average follow-up period was 12mo. The female/male ratio was 13/13. Mean age was 45.65±3.83y (range 26 to 65y). Etiologically, rheumatic arthritis occurred in 6 patients (18.75%), ankylosing spondylitis in 4 (12.50%), HLA-B27 associated uveitis in 3 (9.38%), Vogt-Koyanagi-Harada-associated uveitis in 4 (12.50%) , Behcet's disease in 2 (6.25%), and 7 (21.88%) suffered from unknown diseases. All 32 eyes had varying degrees of improvement at 12mo after surgery, with 2 eyes showing BCVA of 0.1 or below (6.25%), 6 having 0.1-0.5 (18.75%), 18 of 0.5-1.0 (56.25%), and 6 of 1.0 or above (18.75%). No cases with increased IOP were observed. The values of mean CMT was increased at day 1, decreased at 1, 3mo after surgery and increased at 6, 12mo after surgery. No severe uveitis reactions, such as fibrinous exudates in the anterior chamber and exudative membrane formation on the anterior surface of the IOL, were observed after surgery. CONCLUSION: The present studies show that intravitreal injection of Ozudex during cataract operation can provide a new option for the clinical treatment of uveitis-induced cataract.

Objective: Long non-coding RNAs (lncRNAs) have been shown to be associated with the pathogenesis of different kinds of diseases and play important roles in various biological processes. Although numerous lncRNAs have been found, the functions of most lncRNAs and physiological/pathological significance are still in its infancy. Meanwhile, their expression patterns and regulation mechanisms are also far from being fully understood. Methods: In order to reveal functional lncRNAs and identify the key lncRNAs, we develop a new sparse independence component analysis (ICA) method to identify lncRNA-mRNA-miRNA expression co-modules based on the competitive endogenous RNA (ceRNA) theory using the sample-matched lncRNA, mRNA and miRNA expression profiles. The expression data of the three RNA combined together is approximated sparsely to obtain the corresponding sparsity coefficient, and then it is decomposed by using ICA constraint optimization to obtain the common basis and modules. Subsequently, affine propagation clustering is used to perform cluster analysis on the common basis under multiple running conditions to obtain the co-modules for the selection of different RNA elements. Results: We applied sparse ICA to Liver Hepatocellular Carcinoma (LIHC) dataset and the experiment results demonstrate that the proposed sparse ICA method can effectively discover biologically functional expression common modules. Conclusion: It may provide insights into the function of lncRNAs and molecular mechanism of LIHC. Clinical and Translational Impact Statement–The results on LIHC dataset demonstrate that the proposed sparse ICA method can effectively discover biologically functional expression common modules, which may provide insights into the function of IncRNAs and molecular mechanism of LIHC.

Objective: The mechanisms of chondrocytes ferroptosis in osteoarthritis (OA) have not yet been fully elucidated. This study aimed to identify key ferroptosis related genes (FRGs) involved in chondrocytes ferroptosis. Methods: LASSO, SVM-RFE, and receiver operating characteristic curve (ROC) were performed to screen key differentially expressed FRGs (DEFRGs). Functional analyses were conducted using GO, and KEGG analyses. Unsupervised clustering analysis was used to identify ferroptosis related patterns. The CeRNA network was constructed to predict the upstream miRNAs and lncRNAs. Finally, we validated the role of EGFR in chondrocytes ferroptosis using in vivo and in vitro experiments. Results: A total of 42 DEFRGs were identified between OA and normal cartilages. GO and KEGG analyses indicated that these DEFRGs were significantly engaged in ferroptosis related biological processes and pathways, such as cellular response to oxidative stress, positive regulation of programmed cell death, MAPK and PI3K-Akt signaling pathways. Moreover, four key DEFRGs, including ACSF2, AURKA, EGFR, and KLHL24, were considered as potential biomarkers of OA. Moreover, two distinct ferroptosis related patterns were determined, and a total of 882 differentially expressed genes were identified which might participate in extracellular matrix degradation and inflammatory response. In addition, the CeRNA network showed that EGFR could be competitively regulated by 3 lncRNAs and 4 miRNAs. Significantly, the expression of EGFR was downregulated in human OA cartilages, OA mouse model, and erastin induced chondrocytes. EGFR inhibition could induce the occurrence of chondrocytes ferroptosis and ECM degradation which could be reversed by the addition of Ferrostatin-1. Conclusion: Our study has identified ACSF2, AURKA, EGFR, and KLHL24 as ferroptosis-related biomarkers in OA. Furthermore, we have conducted a preliminary investigation into the role of EGFR in regulating chondrocytes ferroptosis. These findings offer novel insights into the molecular mechanisms underlying OA.

We report on the realization of Bose–Einstein condensation (BEC) of 168Er atoms in a crossed optical dipole trap. A magneto-optical trap is realized with just one laser driving the narrow-line transition which increases the phase space density and facilitates the evaporative cooling. A pure BEC with 3 × 104 atoms is achieved by forced evaporative cooling. The complex Feshbach resonance and anisotropic expansion of 168Er are investigated by the loss spectroscopy and controlling the rotating dipoles.

ObjectiveIntermittent theta-burst stimulation (iTBS), which is a form of repetitive transcranial magnetic stimulation (rTMS), can produce 600 pulses to the left dorsolateral prefrontal cortex (DLPFC) in a stimulation time of just over 3 min. The objective of this systematic review was to compare the safety and efficacy of iTBS and high-frequency (≥ 5 Hz) rTMS (HF-rTMS) for patients with treatment-resistant depression (TRD).MethodsRandomized controlled trials (RCTs) comparing the efficacy and safety of iTBS and HF-rTMS were identified by searching English and Chinese databases. The primary outcomes were study-defined response and remission.ResultsTwo RCTs (n = 474) investigating the efficacy and safety of adjunctive iTBS (n = 239) versus HF-rTMS (n = 235) for adult patients with TRD met the inclusion criteria. Among the two included studies (Jadad score = 5), all were classified as high quality. No group differences were found regarding the overall rates of response (iTBS group: 48.0% versus HF-rTMS group: 45.5%) and remission (iTBS group: 30.0% versus HF-rTMS group: 25.2%; all Ps > 0.05). The rates of discontinuation and adverse events such as headache were similar between the two groups (all Ps > 0.05).ConclusionThe antidepressant effects and safety of iTBS and HF-rTMS appeared to be similar for patients with TRD, although additional RCTs with rigorous methodology are needed.

Bats have a very long evolutionary history and are highly differentiated in their physiological functions. Results of recent studies suggest effects of some host factors (e.g., phylogeny and dietary habit) on their gut microbiota. In this study, we examined the gut microbial compositions of 18 different species of bats. Results showed that Firmicutes, Gammaproteobacteria, and Actinobacteria were dominant in all fecal samples of bats. However, the difference in the diversity of gut microbiota among bats of different phylogenies was notable (p = 0.06). Various species of Firmicutes, Actinobacteria, and Gammaproteobacteria were found to contribute to the majority of variations in gut microbiota of all bats examined, and Aeromonas species were much more abundant in bats that feed on both insects and fish than in those of insectivores. The abundance of various species of Clostridium, Euryarchaeota, and ancient bacterial phyla was found to vary among bats of different phylogenies, and various species of Vibrio varied significantly among bats with different dietary habits. No significant difference in the number of genes involved in various metabolic pathways was detected among bats of different phylogenies, but the abundance of genes involved in 5 metabolic pathways, including transcription; replication, recombination, and repair; amino acid transport and metabolism; and signal transduction mechanisms, was different among bats with different dietary habits. The abundance of genes in 3 metabolic pathways, including those involved in stilbenoid, diarylheptanoid, and gingerol biosynthesis, was found to be different between insectivorous bats and bats that feed on both insects and fish. Results of this study suggest a weak association between dietary habit and gut microbiota in most bats but a notable difference in gut microbiota among bats of different phylogenies.

Landslides are major geological hazards and frequently occur in mountainous areas with steep slopes, often causing significant loss. Interferometric Synthetic Aperture Radar (InSAR) has been widely used in landslide measurement over the last three decades. However, InSAR only can measure one-dimensional displacements (i.e. those in the radar’s line of sight (LOS) direction), resulting in the uncertainty between LOS displacement and the real slope displacement. In this paper, based on ascending and descending data from Sentinel-1 satellite, a wide-area potential landslide early identification was carried out using SBAS-InSAR in the whole of Mao County, a mountainous area in western Sichuan (China), with a total of 41 potential landslides successfully detected. Based on the quantitative analysis, the results show that the InSAR LOS measurement values are slope aspect and gradient-dependent. Finally, we innovatively derived a LOS displacement sensitivity map of InSAR in landslide measurement, revealing the relationship between LOS displacement, real displacements on slopes with arbitrary aspects and gradients, and SAR geometric distortion. This is a generalized finding useful for any slopes. It provides theoretical support to acquire and understand the real slope displacement from InSAR landslide measurement, which is vital to assist in correctly interpreting LOS displacement and carrying out subsequent quantitative geological engineering analysis.

Abstract After sequencing, it is common to screen ncRNA according to expression differences. But this may lose a lot of valuable information and there is currently no indicator to characterize the regulatory function and participation degree of ncRNA on transcriptome. Based on existing pathway enrichment methods, we developed a new algorithm to calculating the participation degree of ncRNA in transcriptome (PDNT). Here we analyzed multiple data sets, and differentially expressed genes (DEGs) were used for pathway enrichment analysis. The PDNT algorithm was used to calculate the Contribution value (C value) of each ncRNA based on its target genes and the pathways they participates in. The results showed that compared with ncRNAs screened by log2 fold change (FC) and p-value, those screened by C value regulated more DEGs in IPA canonical pathways, and their target DEGs were more concentrated in the core region of the protein–protein interaction (PPI) network. The ranking of disease critical ncRNAs increased integrally after sorting with C value. Collectively, we found that the PDNT algorithm provides a measure from another view compared with the log2FC and p-value and it may provide more clues to effectively evaluate ncRNA.

Background Hyperphosphatemia and anemia, which are common complications of chronic kidney disease (CKD), can independently contribute to cardiovascular events. Several previous studies have found that the iron-based phosphate binder, ferric citrate (FC), could be beneficial to both hyperphosphatemia and anemia.Methods Relevant literature from PUBMED, EMBASE, the Cochrane Central Register of Controlled Trials (CCRCT) and MEDLINE databases were searched up to 21 February 2022, in order to conduct a meta-analysis to investigate the efficacy, safety and economic benefits of ferric citrate treatment in CKD patients with hyperphosphatemia and anemia. The meta-analysis was conducted independently by two reviewers using the RevMan software (version 5.3).Results In total, this study included 16 randomized clinical trials (RCT) involving 1754 participants. The meta-analysis showed that ferric citrate could significantly reduce the serum phosphorus in CKD patients compared to the placebo control groups (MD −1.76 mg/dL, 95% CI (−2.78, −0.75); p = 0.0007). In contrast, the difference between ferric citrate treatment and active controls, such as non-iron-based phosphate binders, sevelamer, calcium carbonate, lanthanum carbonate and sodium ferrous citrate, was not statistically significant (MD − 0.09 mg/dL, 95% CI (−0.35, 0.17); p = 0.51). However, ferric citrate could effectively improve hemoglobin levels when compared to the active drug (MD 0.43 g/dL, 95% CI (0.04, 0.82); p = 0.03) and placebo groups (MD 0.39 g/dL, 95% CI (0.04, 0.73); p = 0.03). According to eight studies, ferric citrate was found to be cost-effective treatment in comparison to control drugs. Most of the adverse events (AE) following ferric citrate treatment were mild at most.Conclusion Collectively, our review suggests that iron-based phosphate binder, ferric citrate is an effective and safe treatment option for CKD patients with hyperphosphatemia and anemia. More importantly, this alternative treatment may also less expensive. Nevertheless, more scientific studies are warranted to validate our findings.

Long-term denervation leads to the disintegration of nicotinic acetylcholine receptor (nAChR) located at the endplate structure, which translates to deficits in functional activation despite nerve repair. Because of a lack of effective measures to protect AChR expression, we explored the effect of alterations in muscular miR-142a-3p on nAChR. In this study, we constructed a model of miR-142a-3p knockdown by transfecting a miR-142a-3p inhibitor short hairpin RNA (shRNA) into C2C12 myotubes, and we injected this miR-142a-3p inhibitor shRNA into the tibialis anterior (TA) muscle in uninjured mice and in denervated mice by transecting the sciatic nerve. Our results showed that miR-142a-3p knockdown led to an increased number and area of AChR clusters in myotubes in vitro and larger neuromuscular endplates in adult mice. Furthermore, miR-142a-3p knockdown delayed the disintegration of motor endplates after denervation. Last, upon miR-142a-3p knockdown in uninjured and denervated mice, we observed an increase in the mRNA levels of five AChR subunits as well as mRNAs of genes implicated in AChR transcription and AChR clustering. Together, these results suggest that miR-142a-3p may be a potential target for therapeutic intervention to prevent motor endplate degradation following peripheral nerve injury.

Abstract Sepsis is a common complication of combat injuries and trauma, and is defined as a life-threatening organ dysfunction caused by a dysregulated host response to infection. It is also one of the significant causes of death and increased health care costs in modern intensive care units. The use of antibiotics, fluid resuscitation, and organ support therapy have limited prognostic impact in patients with sepsis. Although its pathophysiology remains elusive, immunosuppression is now recognized as one of the major causes of septic death. Sepsis-induced immunosuppression is resulted from disruption of immune homeostasis. It is characterized by the release of anti-inflammatory cytokines, abnormal death of immune effector cells, hyperproliferation of immune suppressor cells, and expression of immune checkpoints. By targeting immunosuppression, especially with immune checkpoint inhibitors, preclinical studies have demonstrated the reversal of immunocyte dysfunctions and established host resistance. Here, we comprehensively discuss recent findings on the mechanisms, regulation and biomarkers of sepsis-induced immunosuppression and highlight their implications for developing effective strategies to treat patients with septic shock.

Background: To investigate the genotype and clinical characteristics of carbapenem-resistant Enterobacteriaceae (CRE) strains in southwest China and provide information on the treatment stopping the spread of the infection. Methods: The clinical information of CRE isolates was collected from 19 hospitals in 12 cities across Sichuan Province, China, between June 2018 and April 2019. The isolates were detected by DNA sequencing of genes encoding carbapenem enzymes and multilocus sequence types (MLSTs). Results: A total of 166 nonrepetitive CRE isolates were isolated during the study period from sputum, blood, urine, and other samples. Klebsiella pneumoniae carbapenemase (KPC) was dominant in Klebsiella pneumoniae (53.9%), followed by New Delhi metallo-β-lactamase (NDM) (42.1%). A total of 43 STs were detected. The most common ST of K. pneumoniae was ST11, and that of Escherichia coli was ST410. Pairwise single nucleotide polymorphism (SNP) distances and the likelihood of local transmission by epidemiology were plotted for each species. About 65% of these pairs had ≤ 20 pairwise SNPs. Conclusion: A large number of CRE strains carried carbapenemase. Although NDM-ST12 K. pneumoniae should not be disregarded, KPC-ST11is the predominant strain. Thus, the possibility of transmission between E. coli and K. pneumoniae could not be ignored.

Biorefinery is pivotal to the sustainability of modern chemical industry. However, since biomass is oxygen-enriched, new and green chemical strategies are required for expanding the biomass derived chemical space. In this work, synthesis of natural products dihydrocapsaicin and dihydrocapsiate was achieved exclusively from lignocellulosic platform chemicals. Natural products dihydrocapsaicin and dihydrocapsiate were synthesized exclusively from lignocellulosic platform chemicals, using furfural (from hemicellulose) and methyl isopropyl ketone (from cellulose) through aldol condensation-hydrolysis-hydrodeoxygenation to synthesize 8-methylnonanoic acid and then combined with vanillin derivates (from lignin). This synthesis demonstrates the feasibility of constructing natural products entirely from renewable biomass platform through green processes. The utilization of inherent functional groups of biomass demonstrates their potential to open up chemical space.

Objective: Klebsiella pneumoniae carbapenemase (KPC)-producing K.pneumoniae has represented a serious health problem in worldwide. The resistance to ceftazidime-avibactam (CAZ-AVI) began to emerge since its approval in 2015. We aim to explore the resistance mechanism of CAZ-AVI. Methods: Phenotypic test and whole-genome sequencing (WGS) analysis were performed in KP-HX0917 and KP-HX1016 Klebsiella pneumoniae isolates, collected from the same patient following treatment with CAZ-AVI. Results: We report a case of emergence of CAZ-AVI resistance in ST 11 KPC-2-producing K. pneumoniae (KP-HX1016) during 14 days of exposure with CZA-AVI. Molecular analysis highlighted the A533C mutation in the blaKPC-2 gene, resulting a D179A substitution in protein sequence, which restored the hydrolysis ability of imipenem and meropenem, but not for ertapenem, and the result of phenotypic test was negative. However, KP-HX0917 produced serine-carbapenemase by phenotypic detection and lost its capacity of hydrolyzing carbapenems. Conclusion: The emergence of CAZ-AVI resistance should arouse our attention, the susceptibility testing should be followed by a combination of phenotypic and molecular methods, to make sure that no potential carbapenemase-producing bacteria are missed.

Abstract Activating mutations of epidermal growth factor receptor (EGFR) contributes to the progression of non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitor (TKI)-targeted therapy has become the standard treatment for NSCLC patients with EGFR-mutations. However, acquired resistance to these agents remains a major obstacle for managing NSCLC. Here, we investigated a novel strategy to overcome EGFR TKI resistance by targeting the nicotinamide N-methyltransferase (NNMT). Using iTRAQ-based quantitative proteomics analysis, we identified that NNMT was significantly increased in EGFR-TKI-resistant NSCLC cells. Moreover, we found that NNMT expression was increased in EGFR-TKI-resistant NSCLC tissue samples, and higher levels were correlated with shorter progression-free survival in EGFR-TKI-treated NSCLC patients. Knockdown of NNMT rendered EGFR-TKI-resistant cells more sensitive to EGFR-TKI, whereas overexpression of NNMT in EGFR-TKI-sensitive cells resulted in EGFR-TKI resistance. Mechanically, upregulation of NNMT increased c-myc expression via SIRT1-mediated c-myc deacetylation, which in turn promoted glycolysis and EGFR-TKI resistance. Furthermore, we demonstrated that the combination of NNMT inhibitor and EGFR-TKI strikingly suppressed the growth of EGFR-TKI-resistant NSCLC cells both in vitro and in vivo. In conclusion, our research indicated that NNMT overexpression is important for acquired resistance to EGFR-TKI and that targeting NNMT might be a potential therapeutic strategy to overcome resistance to EGFR TKI.