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The regenerative capability of the liver is remarkable, but further research is required to understand the role that neutrophils play in this process. In the present study, we reanalyzed single‐cell RNA sequencing data from a mouse partial hepatectomy (PH) model to track the transcriptional changes in hepatocytes and non‐parenchymal cells. Notably, we unraveled the regenerative capacity of hepatocytes at diverse temporal points after PH, unveiling the contributions of three distinct zones in the liver regeneration process. In addition, we observed that the depletion of neutrophils reduced the survival and liver volume after PH, confirming the important role of neutrophils in liver regeneration. CellChat analysis revealed an intricate crosstalk between neutrophils and macrophages promoting liver regeneration and, using weighted gene correlation network analysis, we identified the most significant genetic module associated with liver regeneration. Our study found that hepatocytes in the periportal zone of the liver are more active than in other zones, suggesting that the crosstalk between neutrophils and macrophages might be a potential target for liver regeneration treatment.

Abstract Severe cytokine release syndrome (sCRS) and immune effector cell‐associated neurotoxicity syndrome (ICANS) have limited the widespread use of chimeric antigen receptor T (CAR T)‐cell therapy. We designed a novel anti‐CD19 CAR (ssCART‐19) with a small hairpin RNA (shRNA) element to silence the interleukin‐6 (IL‐6) gene, hypothesizing it could reduce sCRS and ICANS by alleviating monocyte activation and proinflammatory cytokine release. In a post hoc analysis of two clinical trials, we compared ssCART‐19 with common CAR T‐cells (cCART‐19) in relapsed/refractory B‐cell acute lymphoblastic leukemia (r/r B‐ALL). Among 87 patients, 47 received ssCART‐19 and 40 received cCART‐19. Grade ≥3 CRS occurred in 14.89% (7/47) of the ssCART‐19 group versus 37.5% (15/40) in the cCART‐19 group (p = 0.036). ICANS occurred in 4.26% (2/47) of the ssCART‐19 group (all grade 1) compared to 15% (2/40) of the cCART‐19 group. Patients in the ssCART‐19 group showed comparable rates of treatment response (calculated with rates of complete remission and incomplete hematological recovery) were 91.49% (43/47) for ssCART‐19 and 85% (34/40) for cCART‐19 (p = 0.999). With a median follow‐up of 21.9 months, cumulative nonrelapse mortality was 10.4% for ssCART‐19 and 13.6% for cCART‐19 (p = 0.33). Median overall survival was 37.17 months for ssCART‐19 and 32.93 months for cCART‐19 (p = 0.40). Median progression‐free survival was 24.17 months for ssCART‐19 and 9.33 months for cCART‐19 (p = 0.23). These data support the safety and efficacy of ssCART‐19 for r/r B‐ALL, suggesting its potential as a promising therapy.

Abstract The mechanisms of anxiety disorders, the most common mental illness, remain incompletely characterized. The ventral hippocampus (vHPC) is critical for the expression of anxiety. However, current studies primarily focus on vHPC neurons, leaving the role for vHPC astrocytes in anxiety largely unexplored. Here, genetically encoded Ca2+ indicator GCaMP6m and in vivo fiber photometry calcium imaging are used to label vHPC astrocytes and monitor their activity, respectively, genetic and chemogenetic approaches to inhibit and activate vHPC astrocytes, respectively, patch‐clamp recordings to measure glutamate currents, and behavioral assays to assess anxiety‐like behaviors. It is found that vHPC astrocytic activity is increased in anxiogenic environments and by 3‐d subacute restraint stress (SRS), a well‐validated mouse model of anxiety disorders. Genetic inhibition of vHPC astrocytes exerts anxiolytic effects on both innate and SRS‐induced anxiety‐related behaviors, whereas hM3Dq‐mediated chemogenetic or SRS‐induced activation of vHPC astrocytes enhances anxiety‐like behaviors, which are reversed by intra‐vHPC application of the ionotropic glutamate N‐methyl‐d‐aspartate receptor antagonists. Furthermore, intra‐vHPC or systemic application of the N‐methyl‐d‐aspartate receptor antagonist memantine, a U.S. FDA‐approved drug for Alzheimer's disease, fully rescues SRS‐induced anxiety‐like behaviors. The findings highlight vHPC astrocytes as critical regulators of stress and anxiety and as potential therapeutic targets for anxiety and anxiety‐related disorders.

Abstract Urbanization alters the thermal and dynamic environment of the local climate system, resulting in significant impacts on precipitation in both urban and adjacent areas. Nevertheless, there remains a significant gap in our understanding of urbanization‐induced effects on asymmetrical, symmetrical, and other precipitation patterns in urban agglomerations (UAs) with divergent background climates and geographic regions at different timescales. Specifically, this asymmetrical change pattern is characterized by an increase in heavy (or light) rainfall and a decrease in light (or heavy) rainfall. Here, we assessed the effects of urbanization on precipitation patterns across 18 UAs situated in diverse background climates and geographical areas in China at different timescales. The results demonstrate that urbanization predominantly alters precipitation patterns in UAs located in the humid region. Specifically, urbanization amplified asymmetrical changes in Yangtze River Delta, Pearl River Delta, Beibu Gulf, Middle Yangtze River, and Guanzhong, but exacerbated symmetrical changes in precipitation in some regions such as Chengdu‐Chongqing. Notably, the urbanization effect demonstrates greater significance at the hourly scale, as exemplified in the Yangtze River Delta, Pearl River Delta, and Middle Yangtze River, where the urban impact is nearly twice as pronounced when compared to the daily scale. Moreover, urbanization had either no effect or has a negative impact on precipitation patterns in UAs located within continental and arid regions. This is related to the intensity of urbanization, background climate and complex topography. This finding implies that urban managers should consider the impact of urbanization on precipitation patterns in different contexts to provide scientific guidance for urban planning.

Abstract Brown carbon (BrC) exhibits a highly complex chemical composition with diverse light‐absorbing properties, which complicates our understanding of its climate impacts. This study examined the impact of molecular characteristics (including molecular mass, unsaturation, oxidation state, and polarity) and heteroatoms on the light‐absorbing properties (absorptivity and wavelength dependence) of BrC from a molecular perspective, based on the ultraviolet‐visible spectra of over 40,000 light‐absorbing substances in aerosol from different sources and ambience. Our findings reveal that the light‐absorptivity of BrC molecules increases with decreasing polarity and O/C ratio, while it rises with higher molecular mass and unsaturation. We developed predictive models for molecular absorptivity based on its double bond equivalent and O/C ratio. In addition, we observed an inverse correlation between absorptivity and wavelength dependence at the molecular level, as determined through mathematical analysis. This molecular‐level understanding provides valuable insights into BrC absorbing mechanisms, facilitating more accurate characterization in atmospheric models.

Abstract The migratory and omnivorous common crane (Grus grus) uses a nature reserve with crucial ecological value that provides supplementary food resources, although the extent of their use by these cranes is unknown. In this study, we used DNA metabarcoding of plants through the chloroplast rbcL gene to investigate the diets of 25 common crane fecal samples and performed analyses in conjunction with supplementary feeding. The results showed that common cranes preferred plants of the families Poaceae and Cyperaceae, similar to common cranes in other nature reserves. Before supplementary feeding, Poaceae and Cyperaceae accounted for 43.83 ± 20.58% and 53.51 ± 19.24%, respectively, while after that, they accounted for 61.23 ± 35.19% and 24.07 ± 28.20%, respectively. The relative abundance of Hordeum increased significantly in January, accounting for 33.88 ± 31.32%, which was mainly affected by supplementary feeding. Therefore, under supplementary feeding, foraging grounds and feeding preferences of common cranes may change correspondingly. The quantity of corn kernels and wheat grains can be increased appropriately in supplementary feeding measures in the nature reserve, and more supplementary feeding sites should be set up in response to the shortage of wild bird food resources. This study applied an effective method to study the diet preference of common cranes under supplementary feeding and further provided insights to improve management measures in the nature reserve.

Brain organoids have been considered as an advanced platform for in vitro disease modeling and drug screening, but numerous roadblocks exist, such as lack of large-scale production technology and lengthy protocols with multiple manipulation steps, impeding the industrial translation of brain organoid technology. Here, we describe the high-speed and large-scale production of midbrain organoids using a high-throughput screening-compatible platform within 30 days. Micro midbrain organoids (µMOs) exhibit a highly uniform morphology and gene expression pattern with minimal variability. Notably, µMOs show dramatically accelerated maturation, resulting in the generation of functional µMOs within only 30 days of differentiation. Furthermore, individual µMOs display highly consistent responsiveness to neurotoxin, suggesting their usefulness as an in vitro high-throughput drug toxicity screening platform. Collectively, our data indicate that µMO technology could represent an advanced and robust platform for in vitro disease modeling and drug screening for human neuronal diseases.

Objective To compare the long‐term efficacy of screw fixation and hemiarthroplasty in elderly patients with undisplaced femoral neck fractures. Methods We searched Cochrane Library, EMBASE, and MEDLINE from inception to 10 June 2020 to identify studies about undisplaced femoral neck fracture in elderly patients over 65 years of age. The included studies were assessed by two researchers according to the Cochrane risk‐of‐bias criteria and Newcastle–Ottawa Scale. Meta‐analysis was performed with Revman 5.3 software. The odds ratios (OR) and mean differences (MD) were used to compare dichotomous and continuous variables. Results A total of 750 patients were included in this meta‐analysis. In elderly patients, undisplaced femoral neck fracture treated with hemiarthroplasty had a lower implant‐related complication rate (OR, 4.05 [95% CI, 2.38 to 6.89]; P

Abstract The low rate of durable response against relapsed and/or refractory multiple myeloma (RRMM) in recent studies indicates that chimeric antigen receptor T‐cell (CART) treatment is yet to be optimized. This study aims to investigate the safety and efficacy of sequential infusion of CD19‐CART and B‐cell maturation antigen (BCMA)‐CARTs for RRMM with a similar 3 + 3 dose escalation combined with a toxicity sentinel design. We enrolled 10 patients, among whom 7 received autologous infusion and 3 received allogeneic infusion. The median follow‐up time was 20 months. The most common grade 3/4 treatment‐emergent toxicities were hematological toxicities. Cytokine‐release syndrome (CRS) adverse reactions were grade 1/2 in 9 out of 10 subjects. No dose‐limited toxicity (DLT) was observed for BCMA‐CAR‐positive T cells ≤5 × 107/kg), while two patients with dose‐levels of 5–6.5 × 107/kg experienced DLTs. The overall response rate was 90% (five partial responses and four stringent complete responses). Three out of four patients with stringent complete responses to autologous CART had progression‐free survival for over 2 years. The three patients with allogeneic CART experienced disease progression within 2 months. These results evidence the sequential infusion's preliminarily tolerability and efficacy in RRMM, and present a simple and safe design applicable for the establishment of multiple CART therapy.

In many space missions, spacecraft are required to have the ability to avoid various obstacles and finally reach the target point. In this paper, the path planning of spacecraft attitude maneuver under boundary constraints and pointing constraints is studied. The boundary constraints and orientation constraints are constructed as finite functions of path evaluation. From the point of view of optimal time and shortest path, the constrained attitude maneuver problem is reduced to optimal time and path solving problem. To address this problem, a metaheuristic maneuver path planning method is proposed (cross-mutation grey wolf algorithm (CMGWO)). In the CMGWO method, we use angular velocity and control torque coding to model attitude maneuver, which increases the difficulty of solving the problem. In order to deal with this problem, the grey wolf algorithm is used for mutation and evolution, so as to reduce the difficulty of solving the problem and shorten the convergence time. Finally, simulation analysis is carried out under different conditions, and the feasibility and effectiveness of the method are verified by numerical simulation.

Abstract Regenerative farming is a common practice adopted to enhance soil health. Routinely, cheaply measured soil health indicators can be used to predict unknown soil health indicators, which makes analysis simple and fast. The objective of this study was to determine the interaction and relationship between soil health indicators and the effects of regenerative farming practices on soil health indicators. We conducted a comprehensive on‐farm study across Florida, measuring 11 soil health indicators for 592 soil samples that were collected from the surface 15 cm of soil on 13 experimental sites. Sampled fields were conventionally managed or subjected to either cover cropping, organic amendment application, or their combination, and fallow fields as control plots. We tested the Pearson correlation coefficient between 11 soil health indicators and further tested the types of relationships between each indicator using regression analysis. Strong positive correlations (r ≥ + .5 to 1.0) were obtained, especially between organic matter (OM) with maximum water holding capacity (MWHC), cation exchange capacity (CEC), soil protein (SP), and total Kjeldahl nitrogen (TKN); MWHC with CEC, SP, and TKN; TKN with CEC and SP; total phosphorus (TP) with Mehlich‐3 phosphorus (M3P). A strong negative correlation (r ≥ –.5 to –1.0) was observed between bulk density (BD) with OM, MWHC, CEC, and TKN. No significant change in soil health indicators was observed in control plots except for active carbon (AC) and CEC. Organic amendments and a combination of organic amendments with cover crops were effective in improving soil health indicators. However, cover crops alone had no effect on soil health indicators except for CEC and M3K.

Abstract A standardized soil health scoring system would be a beneficial tool for accessing and interpreting the status of soil health in Florida. However, because of the climate variability and diverse soil types, a soil health soring function designed in one location may not be useful for other places. In this study, we focused on developing scoring functions for Florida soil using a soil health indicator database under different land management practices across Florida. A soil health scoring index for 11 soil health indicators was calculated for 398 soil samples using comprehensive assessment of soil health (CASH), linear or nonlinear scoring function, and additive and weighted‐additive methods. Based on communality and weights of total data sets (TDS), Mehlich‐3 phosphorus (M3P) contributed the most, whereas pH contributed the least to the indices. The nonlinear scoring function had higher scores than other scoring functions. Only mixed cropping systems had significant changes in soil health indicators before and after treatment. The principal component analysis (PCA) showed that OM and M3P had the highest loading values compared with other indicators. Therefore, OM and M3P need to be considered if minimum number of indicators is to be measured while examining soil health indices pertinent to Florida soil types and land management practices. Overall, the findings of this study provide a foundation for creating and enhancing soil health indices in Florida.

To evaluate the application, safety and efficacy of the patients treated with intramedullary nailing (IMN) and minimally invasive plate osteosynthesis (MIPO) in distal tibia fractures. Following the Preferred Reporting Items for Systematic Reviews and Meta Analysis (PRISMA) guidelines, we searched databases PubMed, Cochrane library, EMBASE and Web of Science from inception of the database up to 10 October 2018, using the keywords “distal tibia fractures”, “plate”, “intramedullary nailing” and “RCT” to identify randomized clinical trials about distal tibia fractures. The included studies were assessed by two researchers according to the Cochrane risk‐of‐bias criteria. The primary outcome of measurement included operation time, malunion rate, nonunion/delayed union rate, and wound complication. Data analysis was conducted with Review Manager 5.3 software. A total of 10 RCTs involving 911 patients fulfilled the inclusion criteria with 455 patients in the IMN group and 456 patients in the MIPO group. There were no significant differences in radiation time, nonunion or delayed union rate, union time and operation time between the two groups. Patients treated with MIPO had lower incidence of malunion compared with IMN (RR = 1.85, 95%CI: 1.21 to 2.83, P = 1.00), while IMN seemed to have lower surgical incision complications whether in closed or opening fractures (RR = 0.49, 95%CI 0.33 to 0.73, P = 0.43). But in patients classified as 43A, the result of subgroup analysis suggested that there was no significant inwound complication between the two groups. MIPO was superior in preventing malunion compared with IMN, and intramedullary nailing appeared to have lower wound complications. However, in patients with 43A distal tibial fractures, MIPO was more recommended for its prevention of malunion. No matter which method we choose, we should notice and prevent the associated complications.

Background Chronic inflammation plays a significant role in the occurrence and development of non‐small cell lung cancer (NSCLC). Hydroxysafflor yellow A (HSYA), a chemical compound of the yellow color pigments extracted from the safflower, has been widely used in clinical treatment with positive antioxidation, anti‐inflammation, and antitumor effects. However, the role and underlying mechanisms of HYSA on development and progress in inflammation‐mediated NSCLC are unknown. Methods Cell counting kit‐8, colony formation, EdU, cell apoptosis, wound healing, Transwell migration and invasion, and enzyme‐linked immunosorbent assays; flow cytometry; and Western blotting were conducted using human NSCLC cell lines A549 and H1299. Results Lipopolysaccharide (LPS) significantly promoted the proliferation and enhanced colony formation of A549 and H1299 cells, while HYSA notably reversed the effects of LPS. HYSA induced apoptosis of LPS‐mediated A549 and H1299 cells in a dose dependent manner; and remarkably suppressed migration, invasion, and epithelial–mesenchymal transition (EMT), significantly regulated production of LPS‐induced inflammation cytokines, and downregulated protein expression of PI3K/Akt/mTOR and ERK/MAPK signaling pathways in LPS‐induced A549 and H1299 cells. Furthermore, PI3K (LY294002) and ERK (SCH772984) inhibitors remarkably inhibited proliferation, migration, invasion, and EMT, and induced apoptosis in LPS‐mediated A549 and H1299 cells. These effects were even more obvious in the presence of HYSA and LY294002 or SCH772984 compared to those of either agent alone. Conclusion HYSA suppressed LPS‐mediated proliferation, migration, invasion, and EMT in A549 and H1299 cells by inhibiting the PI3K/Akt/mTOR and ERK/MAPK signaling pathways, indicating that HYSA may be a potential candidate to treat inflammation‐mediated NSCLC.

Background. To evaluate the feasibility of using a single device to close multiple atrial septal defects (ASDs) under the guidance of transthoracic echocardiography (TTE) and with the aid of three-dimensional (3D) printing models. Methods. Sixty-two patients with multiple ASDs were retrospectively analyzed. Thirty of these patients underwent TTE-guided closure (3D printing and TTE group) after a simulation of occlusion in 3D printing models. The remaining 32 patients underwent ASD closure under fluoroscopic guidance (conventional group). Closure status was assessed immediately and at 6 months after device closure. Results. Successful transcatheter closure with a single device was achieved in 26 patients in the 3D printing and TTE group and 27 patients in the conventional group. Gender, age [18.8 ± 15.9 (3–51) years in the 3D printing and TTE group; 14.0 ± 11.6 (3–50) years in the conventional group], mean maximum distance between defects, prevalence of 3 atrial defects and large defect distance (defined as distance ≥7 mm), and occluder size used were similarly distributed between groups. However, the 3D printing and TTE group had lower frequency of occluder replacement (3.8% vs 59.3%, p

Employing the tools of multifractal detrended cross-correlation analysis (MF-DCCA) and Diebold–Yilmaz spillover index (D.Y. spillover index), we examine the effect that the foreign investors have on the cross-correlations between the two-segment stock markets, that are the accessible and the inaccessible stock markets, and the other ten respective stock markets. The shares cross-listed by the same corporates on both the A-share and H-share stock markets of China serve as the best sample to compile the two stock indices, which stands for the inaccessible stock market (AHA) and the accessible stock market (AHH), respectively. Empirical results show that the cross-correlations between the two-segment stock markets and the other ten pairs are multifractal, the multifractal strength of cross-correlations is stronger in AHH than AHA, and the intensified growth of the multifractal cross-correlations in AHA can be seen as the increasing of the openness in the inaccessible market. The empirical result of D.Y. spillover index is consistent with the multifractal analysis above, and another interesting finding is that among the selected markets, the three markets with the strongest spillover effects with AHA and AHH are Taiwan, South Korea, and Singapore, respectively, and the weakest one is Australia during the sample scenarios.

Objective: To determine the beneficial effects of intraoperative high-field magnetic resonance imaging (MRI), multimodal neuronavigation, and intraoperative electrophysiological monitoring-guided surgery for treating supratentorial cavernomas. Methods: Twelve patients with 13 supratentorial cavernomas were prospectively enrolled and operated while using a 1.5 T intraoperative MRI, multimodal neuronavigation, and intraoperative electrophysiological monitoring. All cavernomas were deeply located in subcortical areas or involved critical areas. Intraoperative high-field MRIs were obtained for the intraoperative âvisualizationâ of surrounding eloquent structures, âbrain shiftâ corrections, and navigational plan updates. Results: All cavernomas were successfully resected with guidance from intraoperative MRI, multimodal neuronavigation, and intraoperative electrophysiological monitoring. In 5 cases with supratentorial cavernomas, intraoperative âbrain shiftâ severely deterred locating of the lesions; however, intraoperative MRI facilitated precise locating of these lesions. During long-term (>3 months) follow-up, some or all presenting signs and symptoms improved or resolved in 4 cases, but were unchanged in 7 patients. Conclusions: Intraoperative high-field MRI, multimodal neuronavigation, and intraoperative electrophysiological monitoring are helpful in surgeries for the treatment of small deeply seated subcortical cavernomas. Keywords: Cavernoma, Intraoperative electrophysiological monitoring, Intraoperative magnetic resonance imaging, Multimodal neuronavigation

BackgroundPercutaneous coronary intervention has been widely used in the treatment of ischemic heart disease, but vascular restenosis is a main limitation of percutaneous coronary intervention. Our previous work reported that caveolin‐1 had a key functional role in intimal hyperplasia, whereas whether Cavin‐1 (another important caveolae‐related protein) was involved is still unknown. Therefore, we will investigate the effect of Cavin‐1 on neointimal formation. Methods and ResultsBalloon injury markedly reduced Cavin‐1 protein and enhanced ubiquitin protein expression accompanied with neointimal hyperplasia in injured carotid arteries, whereas Cavin‐1 mRNA had no change. In cultured vascular smooth muscle cells (VSMCs), Cavin‐1 was downregulated after inhibition of protein synthesis by cycloheximide, which was distinctly prevented by pretreatment with proteasome inhibitor MG132 but not by lysosomal inhibitor chloroquine, suggesting that proteasomal degradation resulted in Cavin‐1 downregulation. Knockdown of Cavin‐1 by local injection of Cavin‐1 short hairpin RNA (shRNA) into balloon‐injured carotid arteries in vivo promoted neointimal formation. In addition, inhibition or overexpression of Cavin‐1 in cultured VSMCs in vitro prompted or suppressed VSMC proliferation and migration via increasing or decreasing extracellular signal‐regulated kinase phosphorylation and matrix‐degrading metalloproteinases‐9 activity, respectively. However, under basic conditions, the effect of Cavin‐1 on VSMC migration was stronger than on proliferation. Moreover, our results indicated that Cavin‐1 regulated caveolin‐1 expression via lysosomal degradation pathway. ConclusionsOur study revealed the role and the mechanisms of Cavin‐1 downregulation in neointimal formation by promoting VSMC proliferation, migration, and synchronously enhancing caveolin‐1 lysosomal degradation. Cavin‐1 may be a potential therapeutic target for the treatment of postinjury vascular remodeling.

The relative efficacy of different strategies for chronic hepatitis B (CHB) patients with lamivudine resistance (LAM-R) has not yet been systematically studied. Clinical trials were searched in PUBMED, MEDLINE, EMBASE, and CNKI databases up to February 15, 2016. Nine trials including 764 patients met the entry criteria. In direct meta-analysis, TDF showed a stronger antiviral effect than any one of ETV, LAM/ADV, and ADV against LAM-R hepatitis B virus. LAM/ADV therapy was superior to ADV in suppressing viral replication. ETV achieved similar rate of HBV DNA undetectable compared to ADV or LAM/ADV. In network meta-analysis, TDF had higher rates of HBV DNA undetectable compared to ETV (OR, 24.69; 95% CrI: 5.36–113.66), ADV (OR, 37.28; 95% CrI: 9.73–142.92), or LAM/ADV (OR, 21.05; 95% CrI: 5.70–77.80). However, among ETV, ADV, and LAM/ADV, no drug was clearly superior to others in HBV DNA undetectable rate. Moreover, no significant difference in the rate of ALT normalization or HBeAg loss was observed compared the four rescue strategies with each other. TDF appears to be a more effective rescue therapy than LAM/ADV, ETV, or ADV. LAM plus ADV therapy was a better treatment option than ETV or ADV alone for patients with LAM-R.