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As the cornerstone for evaluating the storage capacity of shale reservoirs and assessing the viability of shale gas exploitation, shale pores play a very important role in shale reservoirs. Based on drilling well and test data, deep learning, and artificial intelligence for image analysis, the types, characteristics, structures, and vertical heterogeneity of shale pores were studied. Additionally, we conducted a comprehensive investigation into the sedimentary environment characteristics and their influence on the heterogeneity of shale reservoir pores in the Longmaxi Formation using associated geochemical analyses. The results revealed that the sedimentary environment underwent significant changes in the Longmaxi Formation, characterized by a sea level fall, accelerated sedimentation rates, weakened reducing conditions, decreased palaeoproductivity, and increased terrigenous influx, which led to a decrease in the frequency of organic matter (OM) pores, paralleled by a gradual increase in inorganic pores. In the S1l11−1, S1l11−2, S1l11−3 sections of the Long11 sub-member, OM pores constitute the primary pore type. Conversely, in the S1l11−4 section and the Long12 sub-member, inorganic pores prevail as the primary pore type. Furthermore, the strongly anoxic sections are also pay zones that are not only enriched in OM but also concentrated with OM pores. The S1l11−1 and S1l11−2 sections are characterized by anoxic conditions, with total organic carbon (TOC) content exceeding 4% and abundant biogenic silica. Notably, an increased terrigenous influx adversely impacts the development and preservation of pores in the Long11 sub-member while exerting a dual effect in the Long12 sub-member. The increased terrigenous influx dilutes the OM and decreases the probability of intergranular pores and intragranular pores filled by OM. Moreover, more brittle mineral particles were deposited, which promotes the development and preservation of intergranular and intragranular pores.

The gene editing and synthetic biological tools have led to the implementation of diverse metabolic engineering approaches to enhance the production of specific enzymes. Microbial keratinases can convert keratin wastes into valuable compounds for mankind. Since the market for keratinases cannot be satisfied by production from wild hosts, it is obligatory to develop hosts with high keratinase yields. The intention of this review is to evaluate microbial keratinase advancement through protein engineering, breeding techniques, and fermentation optimization. The main aim of protein engineering is to improve the heat resistance ability and catalytic activity of keratinases by employing mutagenesis methods. Moreover, modifying the expression elements and host engineering are also two unique ways to augment the keratinase yield. Intending to accelerate the production of modified keratinase, this review attempts to highlight the optimization of expression elements, such as promoter engineering, UTR, signal peptide, and codon optimization. Moreover, the approaches of host engineering including strengthening precursor supply, membrane surface engineering, and optimization of secretion pathways were also explained here. Furthermore, it is also essential to optimize the medium composition and fermentation condition for high keratinase yield. This review also addressed the present advancements, difficulties, and tendencies in the field of microbial keratinase production, along with its potential.

Abstract In recent years, immunotherapy, particularly PD-1 antibodies, have significantly enhanced the outcome of gastric cancer patients. Despite these advances, some patients do not respond well to treatment, highlighting the need to understand resistance mechanisms and develop predictive markers of treatment effectiveness. This study retrospectively analyzed data from 106 patients with stage IV gastric cancer who were treated with first-line immunotherapy in combination with chemotherapy. By comparing plasma cytokine levels between patients resistant and sensitive to PD-1 antibody therapy, the researchers identified elevated IL-4 expression in the resistant patients. Mechanical investigations revealed that IL-4 induces metabolic changes in macrophages that activate the PI3K/AKT/mTOR pathway. This alteration promotes ATP production, enhances glycolysis, increases lactic acid production, and upregulates FcγRIIB expression in macrophages. Ultimately, these changes lead to CD8+ T cell dysfunction and resistance to PD-1 antibody therapy in gastric cancer. These findings highlight the role of IL-4-induced macrophage polarization and metabolic reprogramming in immune resistance and verify IL-4 as potential targets for improving treatment outcomes in gastric cancer patients.

Abstract Abscisic acid (ABA) plays a crucial role in promoting plant stress resistance and seed dormancy. However, how ABA regulates rice quality remains unclear. This study identifies a key transcription factor SLR1-like2 (SLRL2), which mediates the ABA-regulated amylose content (AC) of rice. Mechanistically, SLRL2 interacts with NF-YB1 to co-regulate Wx, a determinant of AC and rice quality. In contrast to SLR1, SLRL2 is ABA inducible but insensitive to GA. In addition, SLRL2 exhibits DNA-binding activity and directly regulates the expression of Wx, bHLH144 and MFT2. SLRL2 competes with NF-YC12 for interaction with NF-YB1. NF-YB1 also directly represses SLRL2 transcription. Genetic validation supports that SLRL2 functions downstream of NF-YB1 and bHLH144 in regulating rice AC. Thus, an NF-YB1-SLRL2-bHLH144 regulatory module is successfully revealed. Furthermore, SLRL2 regulates rice dormancy by modulating the expression of MFT2. In conclusion, this study revealed an ABA-responsive regulatory cascade that functions in both rice quality and seed dormancy.

Abstract Exosomes are nanoscale extracellular vesicles present in bodily fluids that mediate intercellular communication by transferring bioactive molecules, thereby regulating a range of physiological and pathological processes. Exosomes can be secreted from nearly all cell types, and the biological function of exosomes is heterogeneous and depends on the donor cell type and state. Recent research has revealed that the levels of exosomes released from the endosomal system increase in cells undergoing programmed cell death. These exosomes play crucial roles in diseases, such as inflammation, tumors, and autoimmune diseases. However, there is currently a lack of systematic research on the differences in the biogenesis, secretion mechanisms, and composition of exosomes under different programmed cell death modalities. This review underscores the potential of exosomes as vital mediators of programmed cell death processes, highlighting the interconnection between exosome biosynthesis and the regulatory mechanisms governing cell death processes. Furthermore, we accentuate the prospect of leveraging exosomes for the development of innovative biomarkers and therapeutic strategies across various diseases.

Introduction: A strong association was previously established between body mass index (BMI) and female reproductive system tumors; however, the causal relationship is unclear. We conducted a Mendelian randomization (MR) study to further explore this association. Methods: Genetic information for BMI was retrieved from a published genome-wide association study involving 339,224 participants. Genetic associations with five common female reproductive system tumors were obtained from the FinnGen, UK Biobank studies, and other large consortia. Results: Genetic predisposition towards BMI exhibits a significant association with multiple tumors of the female reproductive system. Specifically, for every 1-unit increase in BMI log-transformed odds ratio (OR). The OR fluctuations overall for patients with breast cancer ranged from 0.661 to 0.996 (95% confidence interval [CI],0.544-1.000, P

Summary: Background: Toripalimab, a novel PD-1 antibody, is approved for treatment of multiple solid tumors; however, its neoadjuvant use with chemotherapy for triple-negative breast cancer (TNBC) remains unevaluated. Additionally, induction chemotherapy followed by de-escalation of neoadjuvant immunotherapy remains underexplored. Therefore, we conducted a phase II trial investigating a novel neoadjuvant chemoimmunotherapy regimen including de-escalation of immunotherapy for early-stage TNBC. Methods: Chemotherapy and anti-PD-1 therapy were sequentially administered in a neoadjuvant setting to female patients with histologically confirmed stage II–III TNBC between June 9, 2020, and March 24, 2022. Patients received neoadjuvant therapy with four cycles of epirubicin-cyclophosphamide every 2 weeks, followed by toripalimab (240 mg) every 3 weeks plus nab-paclitaxel weekly for 12 weeks. The primary endpoint was total pathological complete response (tpCR; ypT0/is ypN0). Key secondary endpoints included breast pCR (bpCR; ypT0/is), event-free survival and biomarker analysis. Safety was also assessed. This study was registered with ClinicalTrials.gov (NCT04418154). Findings: Among 70 enrolled patients (median age, 51 years; 62.9% stage III), 66 completed treatment without progression and subsequently underwent surgery. The percentages of patients with a tpCR and bpCR were 39 of 70 (55.7%, 95% confidence interval [CI]: 43.3–67.6) and 41 of 70 (58.6%, 95% CI 46.2–70.2), respectively. Sixteen (22.9%) patients experienced grade ≥3 adverse events (AEs), frequently neutropenia (12, 17.1%) and leukopenia (11, 15.7%). The most common immune-related AE was hypothyroidism (5, 7.1%, all grade 1–2). Interpretation: Including 12 weeks of toripalimab in neoadjuvant chemotherapy conferred encouraging activity and manageable toxicity in patients with early TNBC, and this regimen warrants further investigation. Funding: National Natural Science Foundation of China, Junshi Biosciences, and Jiangsu Hengrui Pharmaceuticals.

Abstract Background Prostatic fibrosis, characterized by the accumulation of myofibroblasts and collagen deposition, is closely associated with LUTS and may lead to mechanical obstruction of the urethra. Additionally, Metabolic Syndrome (MetS), characterized by central obesity, high blood sugar, lipid metabolism disorders, and hypertension, is increasingly recognized as a proinflammatory condition linked to prostate inflammation. Methods Clinical data from 108 subjects who underwent transurethral resection of the prostate or bipolar plasmakinetic enucleation of the prostate were prospectively collected between June 2021 and August 2022. Patients were divided in two groups according to whether or not they had a diagnosis of MetS. Specimens were stained with Masson trichrome and the periurethral prostatic fibrosis extent was evaluated using quantitative morphometry. Results Forty-three patients (39.8%) were diagnosed with MetS. Patients with MetS showed a significantly greater extent of prostatic fibrosis than the others (68.1 ± 17.1% vs. 42.5 ± 18.2%, P

This paper proposes a semi-analytical approach for efficient and accurate electromagnetic transient (EMT) simulation of a power grid. The approach first derives a high-order semi-analytical solution (SAS) of the grid’s state-space EMT model using the differential transformation (DT), and then evaluates the solution over enlarged, variable time steps to significantly accelerate the simulations while maintaining its high accuracy on detailed fast EMT dynamics. The approach also addresses switches during large time steps by using a limit violation detection algorithm with a binary search-enhanced quadratic interpolation. Case studies are conducted on EMT models of the IEEE 39-bus system and large-scale systems to demonstrate the merits of the new simulation approach against traditional numerical methods.

Abstract Exosomes are nanoscale extracellular vesicles secreted by cells and enclosed by a lipid bilayer membrane containing various biologically active cargoes such as proteins, lipids, and nucleic acids. Engineered exosomes generated through genetic modification of parent cells show promise as drug delivery vehicles, and they have been demonstrated to have great therapeutic potential for treating cancer, cardiovascular, neurological, and immune diseases, but systematic knowledge is lacking regarding optimization of drug loading and assessment of delivery efficacy. This review summarizes current approaches for engineering exosomes and evaluating their drug delivery effects, and current techniques for assessing exosome drug loading and release kinetics, cell targeting, biodistribution, pharmacokinetics, and therapeutic outcomes are critically examined. Additionally, this review synthesizes the latest applications of exosome engineering and drug delivery in clinical translation. The knowledge compiled in this review provides a framework for the rational design and rigorous assessment of exosomes as therapeutics. Continued advancement of robust characterization methods and reporting standards will accelerate the development of exosome engineering technologies and pave the way for clinical studies. Graphical Abstract

Objective: To systematically evaluate the efficacy and safety of Gong Liu Ning as a complimentary therapy in treatment for uterine fibroids. Methods: Randomized controlled trials on Gong Liu Ning for uterine fibroids from China National Knowledge Infrastructure, Wanfang, China Science and Technology Journal Database, PubMed, Cochrane Library, Embase, Web of Science, Chinese Clinical Trial Registry, and ClinicalTrials.gov were retrieved from inception to March 20, 2023. The risk of bias tool was used to evaluate the quality of the selected studies after they met inclusion and exclusion criteria. The GRADE tool was used to evaluate the quality of evidence, and the RevMan5.3 software was used for data analysis. Results: Twenty studies with 1907 patients were analyzed. The meta-analysis results of 15 studies showed that Gong Liu Ning combined with mifepristone was more efficacious than those observed in controls taking only Western medicine (risk ratio [RR] = 1.22, 95% confidence interval [CI] = [1.11, 1.33], P

Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) is a transmembrane protein that is predominantly expressed by microglia in the brain. The proteolytic shedding of TREM2 results in the release of soluble TREM2 (sTREM2), which is increased in the cerebrospinal fluid of patients with Alzheimer’s disease (AD). It remains unknown whether sTREM2 regulates the pathogenesis of AD. Here we identified transgelin-2 (TG2) expressed on neurons as the receptor for sTREM2. The microglia-derived sTREM2 binds to TG2, induces RhoA phosphorylation at S188, and deactivates the RhoA-ROCK-GSK3β pathway, ameliorating tau phosphorylation. The sTREM2 (77-89) fragment, which is the minimal active sequence of sTREM2 to activate TG2, mimics the inhibitory effect of sTREM2 on tau phosphorylation. Overexpression of sTREM2 or administration of the active peptide rescues tau pathology and behavioral defects in the tau P301S transgenic mice. Together, these findings demonstrate that the sTREM2-TG2 interaction mediates the cross-talk between microglia and neurons. sTREM2 and its active peptide may be a potential therapeutic intervention for tauopathies including AD.

Abstract The International Workshop on Seismic Design and Assessment for Resilience, Robustness and Sustainability of Slope Engineering was held on 13–15 January 2023 on line, focusing on the theme of “Seismic resilience of slope engineering and the concept of resilience-based seismic design (RBSD) for geological disaster prevention and control”. In this workshop, a number of keynote and invited lectures provided an international exchange platform for researchers, industrial engineers and students to share their research, engineering practice and exchange novel ideas on seismic resilience for slope engineering in a way of online. At the same time, during this workshop, technical committee of the ICGdR-TC1 also took this opportunity to hold a working meeting on cutting-edge and strategic issues, and released the Shanghai Declaration on slope engineering.

The ability to estimate wind speed accurately is crucial for optimizing the utilization of wind energy in power systems. The randomness of wind speed and the performance of prediction models are the two issues that have the greatest impact on wind speed prediction. This paper starts from the two aspects of digging wind speed characteristics and optimizing model performance. A new wind speed combined prediction model based on complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN) and improved artificial bee colony algorithm (IABC) to optimize least squares support vector machine (LSSVM) performance. In order to reduce the randomness of the wind speed sequence and increase its predictability, CEEMDAN is first used to break down the wind speed sequence. Secondly, an LSSVM prediction model optimized by an improved artificial bee colony algorithm is established for each subsequence obtained by decomposition; finally, the wind speed forecast value is created by superimposing the results of each subsequence’s prediction. Case studies demonstrate that the combined prediction model put out in this study outperforms other models in terms of prediction performance.

Marek’s disease (MD), caused by the Marek’s disease virus (MDV), is a common infectious tumor disease in chickens and was the first neoplastic disease preventable by vaccination. However, the vaccine cannot completely prevent virulent MDV infections, allowing both the vaccine and virulent MDV to coexist in the same chicken for extended periods. This study aims to investigate the changes in viral load of the very virulent strain Md5 and the rHVT-IBD vaccine in different chicken tissues using a real-time PCR assay. The results showed that the rHVT-IBD vaccine significantly reduced the viral load of MDV-Md5 in different organs, while the load of rHVT-IBD was significantly increased when co-infected with Md5. Additionally, co-infection with Md5 and rHVT-IBD in chickens not only changed the original viral load of both viruses but also affected the positive rate of Md5 at 14 days post-vaccination. The positive rate decreased from 100% to 14.29% (feather tips), 0% (skin), 33.33% (liver), 16.67% (spleen), 28.57% (thymus), 33.33% (bursa), and 66.67% (PBL), respectively. This study enhances our understanding of the interactions between HVT vector vaccines and very virulent MDV in chickens and provides valuable insights for the future development of MD vaccines.

Abstract Barley is one of the world's earliest domesticated crops, which is widely used for beer production, animal feeding, and health care. Barley seed germination, particularly in increasingly saline soils, is key to ensure the safety of crop production. However, the mechanism of salt‐affected seed germination in barley remains elusive. Here, two different colored barley varieties were used to independently study the regulation mechanism of salt tolerance during barley seed germination. High salinity delays barley seed germination by slowing down starch mobilization efficiency in seeds. The starch plate test revealed that salinity had a significant inhibitory effect on α‐amylase activity in barley seeds. Further, NaCl treatment down‐regulated the expression of Amy1, Amy2 and Amy3 genes in germinated seeds, thereby inhibiting α‐amylase activity. In addition, the result of embryogenic culture system in vitro showed that the shoot elongation of barley was significantly inhibited by salt stress. These findings indicate that it is a feasible idea to study the regulation mechanism of salinity on barley seed germination and embryo growth from the aspect of starch‐related source‐sink communication.

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Affected patients experience gradual loss of their spinal cord and cortical motor neurons with consequent muscle weakness and emaciation, and eventual respiratory failure. The pathogenesis of ALS remains largely unknown although the FUS (sarcoma fusion gene) gene is known to be one of the major pathogenic genes. We have generated an induced pluripotent stem cell line SMUSHi002-A from an ALS patient who carries a heterozygous mutation c.1562G > A in FUS. This cell line will serve as a useful model to investigate disease pathogenesis and develop potential therapeutic approaches for ALS.

Abstract Background Treatment of complicated acetabular fracture with internal fixation usually has high risk of failure because of unbefitting fixation. However, evaluation of the biomechanical effect of internal fixation under physiological loading for fracture healing is still generally rarely performed. The purpose of this study is to analyze the biomechanical characteristics of a healed acetabulum with designed internal fixators under gait and to explore the biomechanical relationship between the healed bone and the internal fixator. Methods A patient-specific finite element model of whole pelvis with designed internal fixators was constructed based on the tomographic digital images, in which the spring element was used to simulate the main ligaments of the pelvis. And the finite element analysis under both the combination loading of different phases and the individual loading of each phase during the gait cycle was carried out. The displacement, von Mises stress, and strain energy of both the healed bone and the fixation were calculated to evaluate the biomechanical characteristics of the healed pelvis. Results Under the combination loading of gait, the maximum difference of displacement between the left hip bone with serious injury and the right hip bone with minor injury is 0.122 mm, and the maximum stress of the left and right hemi-pelvis is 115.5 MPa and 124.28 MPa, respectively. Moreover, the differences of average stress between the bone and internal fixators are in the range of 2.3–13.7 MPa. During the eight phases of gait, the stress distribution of the left and right hip bone is similar. Meanwhile, based on the acetabular three-column theory, the strain energy ratio of the central column is relatively large in stance phases, while the anterior column and posterior column of the acetabular three-column increase in swing phases. Conclusions The acetabular internal fixators designed by according to the anatomical feature of the acetabulum are integrated into the normal physiological stress conduction of the pelvis. The design and placement of the acetabular internal fixation conforming to the biomechanical characteristics of the bone is beneficial to the anatomical reduction and effective fixation of the fracture, especially for complex acetabular fracture.

In this research, the different methods (acid extraction, alkaline extraction and enzymatic extraction) were used to extract soluble dietary fiber (SDF) from pomegranate peel and compared with water extraction. Results revealed that all three extraction methods influenced the structure, physicochemical and functional properties of SDF. Especially, SDF extracted by enzymes (E-SDF) and SDF extracted by alkali (A-SDF) had higher yield (27.30% and 27.17%), molecular weight and thermal stability than SDF extracted by water (W-SDF). Higher oil holding capacity (OHC) was found in SDF extracted by acid (C-SDF) (3.18 g/g), A-SDF (3.18 g/g) and E-SDF (5.36 g/g) compared with W-SDF. In addition, A-SDF showed the smallest particle size, lowest ζ-potential and highest viscosity among the tested samples. E-SDF presented a more porous structure, better glucose adsorption capacity (GAC) and antioxidant activity than C-SDF and A-SDF. To sum up, A-SDF and E-SDF may have great potential to be functional food ingredients in the food industry.

Neurodegenerative diseases (NDDs) pose an increasingly prevalent threat to the well-being and survival of elderly individuals worldwide. NDDs include Alzheimer’s disease (AD), Parkinson’s disease (PD), Huntington’s disease (HD), amyotrophic lateral sclerosis (ALS), and so on. They are characterized by progressive loss or dysfunction of neurons in the central or peripheral nervous system and share several cellular and molecular mechanisms, including protein aggregation, mitochondrial dysfunction, gene mutations, and chronic neuroinflammation. Glycogen synthase kinase-3 beta (GSK-3β) is a serine/threonine kinase that is believed to play a pivotal role in the pathogenesis of NDDs. Here we summarize the structure and physiological functions of GSK3β and explore its involvement in NDDs. We also discussed its potential as a therapeutic target.

BackgroundTau phosphorylation is a pathological hallmark of Alzheimer’s disease (AD). Previously, we reported that the γ-adducin 1–357 fragment is present in the brains of AD patients. However, it remains unknown how γ-adducin regulates tau phosphorylation.ObjectiveThe aim of this project is to investigate the effects of the γ-adducin 1–357 fragment on tau phosphorylation and the kinases involved in this process.MethodsFull-length γ-adducin or the γ-adducin 1–357 fragment was expressed in HEK293 cells, SH-SY5Y cells, and primary neurons. The phosphorylation of tau Ser396 was determined using Western blot and immunofluorescence. Tau P301S transgenic mice were injected with adeno-associated virus encoding full-length γ-adducin or γ-adducin 1–357 fragment to determine the phosphorylation of tau.ResultsThe γ-adducin 1–357 fragment enhances tau phosphorylation at Ser396. Additionally, the expression of the γ-adducin 1–357 fragment leads to the activation of glycogen synthase kinase-3β (GSK-3β). This effect was mitigated by the GSK-3β inhibitor 4-Benzyl-2-methyl-1,2,4-thiadiazolidine-3,5-dione (TDZD-8).ConclusionThe γ-adducin 1–357 fragment enhances tau phosphorylation by activating GSK3β. These results support that the fragmentation of γ-adducin may play a pivotal role in tau pathology.

Abstract This study evaluated the impact of elevated body mass index (BMI) on short- and long-term outcomes of in-vitro fertilization (IVF)/intracytoplasmic sperm injection (ICSI) treatments. A total of 7229 patients undergoing IVF/ICSI fresh cycles and subsequent frozen embryo transfer cycles from 2014 to 2020 were divided into normal (18.5–24.9 kg/m2) and high BMI (≥ 25 kg/m2) groups. Ovarian response, pregnancy outcomes, and safety of both mother and fetus were the main outcome measures. Furthermore, multivariate analysis was used to determine whether BMI was associated with cumulative live birth rate (CLBR). Results showed that for younger women (

Accurate and reliable wind speed prediction is essential for the exploitation and utilization of the wind energy. In this paper, a novel hybrid multi-step wind speed prediction model is proposed based on complete ensemble empirical mode decomposition with adaptive noise (CEEMDAN), robust local mean decomposition (RLMD), and improved whale optimization algorithm (IWOA), and long-term and short-term memory network (LSTM). CEEMDAN is utilized to decompose the wind speed series into a number of intrinsic mode functions, and the RLMD is used to the second step decompose the most non-stationary intrinsic mode function into a series of product functions. After the two-step decomposition, a group of new subsequences is formed. The long-term and short-term memory network (LSTM) prediction model is constructed for every subsequence and an improved whale optimization algorithm (IWOA) is used to optimize key parameters affecting the prediction performance of the LSTM model. And at last, the subsequence prediction results are superimposed to provide the final prediction results. The effectiveness and advancement of the proposed hybrid model is verified by employing wind speed data from two different wind farms. And according to the experimental results and comparison, it can be found that the proposed model can provide better performance than the seven compared models.

Abstract Background Hybrid total hip replacement (THR) is commonly used in the management of proximal femur fractures in elderly individuals. However, in the context of the revision, the literature on hybrid THR is limited, and differences in the long-term survival outcomes reported in the literature are obvious. This retrospective study aimed to evaluate the long-term survival of hybrid THR for failed proximal femoral nail antirotation (PFNA) in elderly individuals aged ≥ 75 years. Methods An observational cohort of 227 consecutive individuals aged ≥ 75 years who experienced hybrid THRs following prior primary PFNAs was retrospectively identified from the Joint Surgery Centre, the First Affiliated Hospital, Sun Yat-sen University. Implant survival was estimated using the Kaplan–Meier method. The primary end point was the implant survivorship calculated using the Kaplan–Meier method with revision for any reason as the end point; secondary end points were the function score measured using the modified Harris Hip Score (mHHS) and the incidence of main orthopaedic complications. Results In total, 118 individuals (118 THRs) were assessed as available. The median follow-up was 10 (3–11) years. The 10-year survivorship with revision for any reason as the endpoint was 0.914 (95% confidence interval [CI], 0.843–0.960). The most common indication for revision was aseptic loosening (70.0%), followed by periprosthetic fracture (30.0%). At the final follow-up, the median functional score was 83.6 (79.0–94.0). Among the 118 patients included in this study, 16 experienced 26 implant-related complications. The overall incidence of key orthopaedic complications was 13.5% (16/118). Conclusion For patients aged ≥ 75 years old with prior failed PFNAs, hybrid THR may yield satisfactory long-term survival, with good functional outcomes and a low rate of key orthopaedic complications.

BackgroundChimeric antigen receptor (CAR) T-cell therapy has demonstrated high initial complete remission (CR) rates in B-cell acute lymphoblastic leukemia (B-ALL) patients, including those who relapsed after transplant. However, the duration of remission requires improvements. Whether bridging to a second allogeneic hematopoietic stem cell transplant (allo-HSCT) after CAR-T therapy can improve long-term survival remains controversial. We retrospectively analyzed long-term follow-up data of B-ALL patients who relapsed post-transplant and received CAR-T therapy followed by consolidation second allo-HSCT to investigate whether such a treatment sequence could improve long-term survival.MethodsA single-center, retrospective study was performed between October 2017 and March 2022, involving 95 patients who received a consolidation second transplant after achieving CR from CAR-T therapy.ResultsThe median age of patients was 22.8 years (range: 3.3-52.8) at the second transplant. After the first transplant, 71 patients (74.7%) experienced bone marrow relapse, 16 patients (16.8%) had extramedullary relapse, 5 patients (5.3%) had both bone marrow and extramedullary relapse and 3/95 patients (3.2%) had positive minimal residual disease (MRD) only. Patients received autologous (n=57, 60.0%) or allogeneic (n=28, 29.5%) CAR-T cells, while 10 patients (10.5%) were unknown. All patients achieved CR after CAR-T therapy. Before second HSCT, 86 patients (90.5%) were MRD-negative, and 9 (9.5%) were MRD-positive. All second transplant donors were different from the first transplant donors. The median follow-up time was 623 days (range: 33-1901) after the second HSCT. The 3-year overall survival (OS) and leukemia-free survival (LFS) were 55.3% (95%CI, 44.3-66.1%) and 49.8% (95%CI, 38.7-60.9%), respectively. The 3-year relapse incidence (RI) and non-relapse mortality (NRM) were 10.5% (95%CI, 5.6-19.6%) and 43.6% (95%CI, 33.9-56.2%), respectively. In multivariate analysis, the interval from CAR-T to second HSCT ≤90 days was associated with superior LFS(HR, 4.10, 95%CI,1.64-10.24; p=0.003) and OS(HR, 2.67, 95%CI, 1.24-5.74, p=0.012), as well as reduced NRM (HR, 2.45, 95%CI, 1.14-5.24, p=0.021).ConclusionsOur study indicated that CAR-T therapy followed by consolidation second transplant could significantly improve long-term survival in B-ALL patients who relapsed post-transplant. The second transplant should be considered in suitable patients and is recommended to be performed within 90 days after CAR-T treatment.

BackgroundPrevious studies have shown that abnormal increases in autoimmune antibodies in pregnant women may increase the risk of maternal thrombosis. However, at our hospital, two pregnant women presented with umbilical artery thrombosis and positive maternal autoantibodies were detected in both, which led us to consider whether maternal autoantibodies also played a role in umbilical artery thrombosis.Case presentationCase 1: Fetal ultrasound of a 34-year-old pregnant woman at 30+4 weeks gestation showed two umbilical arteries, with an inner diameter of approximately 0.15 cm for the smaller was artery. However, only a single umbilical artery blood flow signal was detected. Due to fetal distress, which was noted on abnormal cardiotocography and Doppler ultrasound, an emergency cesarean section was performed at 31+1 weeks gestation. The Apgar score of the newborn was 3-8-8. Umbilical cord examination detected thrombosis in the two umbilical arteries. Moreover, blood test results during pregnancy showed nRNP/Sm antibody (+) and SS antibody (+++). Case 2: The first systematic ultrasound of a 33-year-old twin pregnancy at 24+3 weeks gestation was normal, but routine fetal ultrasound at 27+1 weeks gestation showed only one umbilical artery between fetus A and the placenta. Blood test results showed that the patient was anti-nRNP/Sm antibody (+) in the rheumatoid immune activity test at 27+3 weeks gestation. An emergency cesarean section was performed at 34+6 weeks gestation because of the single umbilical artery and abnormal maternal coagulation. Both umbilical cords of fetus A and B blood test results showed anti-nRNP/Sm antibody (++). The pathological examination of the umbilical cord and placenta showed the presence of old thrombosis in one of the umbilical arteries of fetus A.ConclusionsAbnormal maternal autoantibodies may be a risk factor for umbilical artery thrombosis. For these pregnant women, conducting more detailed ultrasound monitoring might get early detection of UAT formation and avoid the occurrence of adverse pregnancy outcomes.

Although targeted therapy for human epidermal growth factor receptor 2 (HER2)-positive breast cancer has significantly prolonged survival time and improved patients’ quality of life, drug resistance has gradually emerged. This study explored the mechanisms underlying the effect of the motor neuron and pancreatic homeobox 1 (MNX1) genes on drug sensitivity in HER2-positive breast cancer. From July 2017 to 2018, core needle biopsies of HER2-positive breast cancer were collected from patients who received paclitaxel, carboplatin, and trastuzumab neoadjuvant therapy at our center. Based on treatment efficacy, 81 patients were divided into pathological complete response (pCR) and non-pCR groups. High-throughput RNA sequencing results were analyzed along with the GSE181574 dataset. MNX1 was significantly upregulated in the pCR group compared with the non-pCR group in both sequencing datasets, suggesting that MNX1 might be correlated with drug sensitivity in HER2-positive breast cancer. Meanwhile, tissue array results revealed that high MNX1 expression corresponded to a good prognosis. In vitro functional tests showed that upregulation of MNX1 significantly increased the sensitivity of HER2-positive breast cancer cells to lapatinib and pyrotinib. In conclusion, MNX1 may serve as a prognostic marker for patients with HER2-positive breast cancer, and its expression may facilitate clinical screening of patients sensitive to anti-HER2-targeted therapy.

Abstract We are concerned with the question of constructing a new type of solution to the problem with χ ( 2 ) $\chi ^{(2)}$ nonlinearities 0.1 { − Δ u + P ( x ) u = α u v , in R N , − Δ v + Q ( x ) v = α 2 u 2 + β v 2 , in R N , where P ( x ) = P ( | x | ) $P(x)=P(|x|)$ and Q ( x ) = Q ( | x | ) $Q(x)=Q(|x|)$ are positive bounded radial potentials, 3 ≤ N < 6 $3\leq N 0 $\alpha >0$ and α > β $\alpha >\beta $ . Assuming that the potentials P ( x ) $P(x)$ and Q ( x ) $Q(x)$ satisfy certain conditions, the existence of a new type of solutions is proved.

An earth dam in service is a complex system that has different dynamic failure modes under different ground motion excitations with a certain correlation between the different failure modes. However, because of the nonlinear dynamic coupling effect of the randomness of the earthquake ground motion and the nonlinearity of the geotechnical parameters, traditional deterministic analyses cannot adequately consider the failure mechanisms of earth rock dams subjected to earthquake excitation, resulting in unexpected and uncontrollable local failure modes or weak failure areas; this makes the seismic dynamic performance of earth rock dams subjected to strong earthquake excitation non-optimal. Accordingly, the main dynamic failure modes and failure mechanisms of earth rock dams under seismic dynamic action are studied based on the nonlinear stochastic dynamics method and the first passage theory, combined with a time-domain nonlinear dynamic time-history analysis. Our results indicate that the seismic dynamic reliability of earth dam under ground motion excitation is far less than that under different single failure modes. Seismic reinforcement or heightening measures based on the overall seismic dynamic reliability can be used to effectively resist strong earthquake disasters encountered by earth rock dams in the future and optimize the seismic dynamic performance of earth rock dams.

Given the widespread application of the lime precipitation process for arsenic removal in the smelting of arsenic-containing minerals, the resourcefulness of calcium arsenate use has received increasing attention. In general, more types of arsenate have different high-temperature characteristics, and the slag type is complicated under mixed reduction roasting and difficult to recover. Additionally, arsenate in the form of calcium arsenate is a more common and inexpensive product in the metallurgical process. Because whether it is arsenic-containing wastewater, arsenic slag, arsenate, and so on, the material can be separated from the system by inexpensive lime precipitation or calcification transformation in simple metallurgical equipment to generate calcium arsenate. Therefore, this paper was devoted to preparing commercially valuable metallic monomers of arsenic by carbon thermal roasting reduction of calcium arsenate and to starting scientific research to advance the harmless treatment of arsenic hazardous waste to arsenic resource recovery and use. Among them, thermogravimetric analysis shows that the mass loss of calcium arsenate mixed with carbon powder pyrolysis is divided into 3 stages: stages 1 and 2 are water loss processes, and stage 3 involves the carbon reduction of calcium arsenate to generate CaO and arsenic vapor. It is found that the stage III reaction mechanism could be explained using the phase boundary reaction kinetic model. The experimental results of single-factor conditions show that the arsenic volatilization rate reaches 99.94% at a constant temperature of 1000 °C for 60 min and a carbon allotment factor of 1.4. The characterization of the relevant products in the reaction system by X-ray diffractometer (XRD) and scanning electron microscope energy spectrometer (SEM‒EDS) show that the arsenic product is mainly flaked metallic arsenic and amorphous powdered arsenicunder better conditions, and the roasted residue is CaO.

Abstract The pathological hallmark of Parkinson’s disease (PD) is the presence of Lewy bodies (LBs) with aggregated α-synuclein being the major component. The abnormal α-synuclein aggregates transfer between cells, recruit endogenous α-synuclein into toxic LBs, and finally trigger neuronal injury. However, the molecular mechanisms mediating the aggregation and transmission of pathological α-synuclein remain unknown. Previously we found that cofilin 1, a member of the actin-binding protein, promotes the aggregation and pathogenicity of α-synuclein in vitro. Here we further investigated the effect of cofilin 1 in mouse models of PD. We found that the mixed fibrils composed of cofilin 1 and α-synuclein are more pathogenic to mice and more prone to propagation than pure α-synuclein fibrils. Overexpression of cofilin 1 enhances the seeding and spreading of α-synuclein aggregates, and induces PD-like behavioral impairments in mice. Together, these results illustrate the important role of cofilin 1 in the pathogenicity and transmission of α-synuclein during the onset and progression of PD.

Summary: The molecular mechanisms mediating the aggregation and transmission of tau in AD remain unclear. Here, we show that the actin-binding protein cofilin is cleaved by a cysteine protease asparagine endopeptidase (AEP) at N138 in the brains of patients with AD. The AEP-generated cofilin 1-138 fragment interacts with tau and promotes its aggregation. The mixed fibrils consisting of cofilin 1-138 and tau are more pathogenic to cells than pure tau fibrils. Furthermore, overexpression of cofilin 1-138 in the brain facilitates the propagation of pathological tau aggregates and promotes AD-like cognitive impairments in tau P301S mice. However, mice infected with adeno-associated viruses (AAVs) encoding an AEP-uncleavable cofilin mutant show attenuated tau pathology and cognitive impairments compared with mice injected with AAVs encoding wild-type cofilin. Together, these observations support the role of the cofilin 1-138 fragment in the aggregation and transmission of tau pathology during the onset and progression of AD.

IntroductionWe aimed to evaluate prognostic factors of a second allogeneic stem cell transplantation (allo-HSCT2) among hematological malignancy patients who have relapsed after the first allo-HSCT(allo-HSCT1).MethodsWe retrospectively analyzed 199 hematological malignancy patients who received allo-HSCT2 as a salvage treatment post allo-HSCT1 relapse between November 2012 and October 2021.ResultsThe median age at allo-HSCT2 was 23 (range: 3-60) years. The median time to relapse after HSCT1 was 9 (range: 1-72) months. Prior to allo-HSCT2, patients had the following hematopoietic cell transplantation-comorbidity indexes (HCT-CI): 127 with a score of 0, 52 with a score of 1, and 20 with a score of 2 or greater. Fifty percent of patients received chimeric antigen receptor (CAR) T-cell therapy following HSCT1 relapse. Disease status was minimal residual disease (MRD)-negative complete remission (CR) among 119 patients, MRD-positive CR among 37 patients and non-remission (NR) for 43 patients prior to allo-HSCT2. Allo-HSCT2 was performed from a new donor in 194 patients (97.4%) and 134 patients (67.3%) received a graft with a new mismatched haplotype. The median follow-up time was 24 months (range: 6-98 months), and the 2-year OS and LFS were 43.8% ± 4.0% and 42.1% ± 4.1%, respectively. The 2-year cumulative incidence of relapse (CIR) and non-relapse mortality (NRM) was 30.0%±4.8% and 38.5%±3.8%, respectively. Cox regression multivariate analysis showed that disease statusof MRD-negative CR, HCT-CI score of 0 prior to allo-HSCT2, and new mismatched haplotype donor were predictive factors of improved OS and LFS compared to patients without these characteristics. Based on these three favorable factors, we developed a predictive scoring system for patients who received allo-HSCT2. Patients with a prognostic score of 3 who had the three factors showed a superior 2-year OS of 63.3% ± 6.7% and LFS of 63.3% ± 6.7% and a lower CIR of 5.5% ± 3.1% than patients with a prognostic score of 0. Allo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 —disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.ConclusionsAllo-HSCT2 is feasible and patients with good prognostic features prior to allo-HSCT2 —disease status of CR/MRD- and HCT-CI score of 0 as well as a second donor with a new mismatched haplotype could have the maximal benefit from the second allo-HSCT.

Maneb, a widely-used dithiocarbamate fungicide, remains in the environment and exerts adverse health effects. Epidemiological evidence shows that maneb exposure is associated with a higher risk of Parkinson’s disease (PD), one of the most common neurodegenerative diseases. However, the molecular mechanisms underlying maneb-induced neurotoxicity remain unclear. Here we investigated the toxic effects and the underlying mechanisms of maneb on the degeneration of dopaminergic cells and α-synuclein in A53T transgenic mice. In SH-SY5Y cells, exposure to maneb reduces cell viability, triggers neuronal apoptosis, induces mitochondrial dysfunction, and generates reactive oxidative species (ROS) in a dose-dependent manner. Furthermore, Western blot analysis found that the mitochondrial apoptosis pathway (Bcl-2, Bax, cytochrome c, activated caspase-3) and the PKA/CREB signaling pathway (PKA, PDE10A, CREB, p-CREB) were changed by maneb both in vitro and in vivo. In addition, the activation of the mitochondrial apoptosis pathway induced by maneb was attenuated by activating PKA. Therefore, these results suggest that the PKA/CREB signaling pathway is involved in maneb-induced apoptosis. This study provides novel insights into maneb-induced neurotoxicity and the underlying mechanisms, which may serve as a guide for further toxicological assessment and standard application of maneb.

Galectin-9 (Gal-9) is a crucial immunoregulatory mediator in the central nervous system. Microglial activation and neuroinflammation play a key role in the degeneration of dopaminergic neurons in the substantia nigra (SN) in Parkinson’s disease (PD). However, it remains unknown whether Gal-9 is involved in the pathogenesis of PD. We found that MPP+ treatment promoted the expression of Gal-9 and pro-inflammatory cytokines (IL-6, IL-1β, TNF-α, and MIP-1α) in a concentration-dependent manner in BV2 cells. Gal-9 enhanced neurodegeneration and oxidative stress induced by MPP+ in SH-SY5Y cells and primary neurons. Importantly, deletion of Gal-9 or blockade of Tim-3 ameliorated microglial activation, reduced dopaminergic neuronal loss, and improved motor performance in an MPTP-induced mouse model of PD. These observations demonstrate a pathogenic role of the Gal-9/Tim-3 pathway in exacerbating microglial activation, neuroinflammation, oxidative stress, and dopaminergic neurodegeneration in the pathogenesis of PD.

Introduction The aim of this retrospective study was to assess the clinical outcomes of cemented or uncemented total hip arthroplasty (CTHA or UTHA) following prior failed proximal femoral nail antirotation (PFNA) fixation in patients with intertrochanteric femur fractures (IFFs). Materials and methods Data from 244 patients with IFFs who experienced a conversion of PFNA to CTHA (n = 120) or to UTHA (n = 124) due to screw cut-out, mal/nonunion, or osteonecrosis during 2008-2018 were retrospectively analyzed. Follow-up occurred 1, 3, 6, and 12 months postoperatively and yearly thereafter. The primary outcome was the incidence of orthopedic complications; the secondary outcome was the Harris hip score (HHS). Results The median follow-up was 60 months (range, 50-67 months). The incidences of orthopedic complications were 10% in the PFNA to CTHA group and 19.3% in the PFNA to UTHA group (P = .040). Significant differences were also observed regarding the incidence of prosthesis revision (1.7% for PFNA to CTHA vs 7.2% for PFNA to UTHA, P = .036). From the three years after conversion surgery to the final follow-up, significant differences were detected in HHS between groups (each P < .05). At the final follow-up, a statistically significant difference was detected in the HHS (79.54±18.85 for PFNA to CTHA vs. 75.26±18.27 for PFNA to UTHA, P = .014). Conclusion The results of the study may demonstrate a significant statistical advantage with respect to the orthopedic complication rate and HHS in favor of CTHA compared to UTHA in patients with failed PFNA.

Iturin A is a biosurfactant with various applications, and its low synthesis capability limits its production and application development. Fatty acids play a critical role in cellular metabolism and target product syntheses, and the relationship between fatty acid supplies and iturin A synthesis is unclear. In this study, we attempted to increase iturin A production via strengthening fatty acid synthesis pathways in Bacillus amyloliquefaciens. First, acetyl-CoA carboxylase AccAD and ACP S-malonyltransferase fabD were overexpressed via promoter replacement, and iturin A yield was increased to 1.36 g/L by 2.78-fold in the resultant strain HZ-ADF1. Then, soluble acyl-ACP thioesterase derived from Escherichia coli showed the best performance for iturin A synthesis, as compared to those derived from B. amyloliquefaciens and Corynebacterium glutamicum, the introduction of which in HZ-ADF1 further led to a 57.35% increase of iturin A yield, reaching 2.14 g/L. Finally, long-chain fatty acid-CoA ligase LcfA was overexpressed in HZ-ADFT to attain the final strain HZ-ADFTL2, and iturin A yield reached 2.96 g/L, increasing by 6.59-fold, and the contents of fatty acids were enhanced significantly in HZ-ADFTL2, as compared to the original strain HZ-12. Taken together, our results implied that strengthening fatty acid supplies was an efficient approach for iturin A production, and this research provided a promising strain for industrial production of iturin A.

Background: Breast cancer (BC) is the most common malignant tumour, and its heterogeneity is one of its major characteristics. N6-methyladenosine (m6A), N1-methyladenosine (m1A), alternative polyadenylation (APA), and adenosine-to-inosine (A-to-I) RNA editing constitute the four most common adenosine-associated RNA modifications and represent the most typical and critical forms of epigenetic regulation contributing to the immunoinflammatory response, tumorigenesis and tumour heterogeneity. However, the cross-talk and potential combined profiles of these RNA-modified proteins (RMPs) in multivariate prognostic patterns of BC remain unknown.Methods: A total of 48 published RMPs were analysed and found to display significant expression alterations and genomic mutation rates between tumour and normal tissues in the TCGA-BRCA cohort. Data from 4188 BC patients with clinical outcomes were downloaded from the Gene Expression Omnibus (GEO), the Cancer Genome Atlas (TCGA), and the Molecular Taxonomy of Breast Cancer International Consortium (METABRIC), normalized and merged into one cohort. The prognostic value and interconnections of these RMPs were also studied. The four prognosis-related genes (PRGs) with the greatest prognostic value were then selected to construct diverse RMP-associated prognostic models through univariate Cox (uniCox) regression analysis, differential expression analysis, Least absolute shrinkage and selection operator (LASSO) regression and multivariate Cox (multiCox) regression. Alterations in biological functional pathways, genomic mutations, immune infiltrations, RNAss scores and drug sensitivities among different models, as well as their prognostic value, were then explored.Results: Utilizing a large number of samples and a comprehensive set of genes contributing to adenosine-associated RNA modification, our study revealed the joint potential bio-functions and underlying features of these diverse RMPs and provided effective models (PRG clusters, gene clusters and the risk model) for predicting the clinical outcomes of BC. The individuals with higher risk scores showed poor prognoses, cell cycle function enrichment, upregulation of stemness scores, higher tumour mutation burdens (TMBs), immune activation and specific drug resistance. This work highlights the significance of comprehensively examining post-transcriptional RNA modification genes.Conclusion: Here, we designed and verified an advanced forecasting model to reveal the underlying links between BC and RMPs and precisely predict the clinical outcomes of multivariate prognostic patterns for individuals.

Abstract Hepatocellular carcinoma (HCC) is usually associated with varying degrees of cirrhosis. Among cirrhotic patients with solitary HCC in the absence of macro-vascular invasion, whether tumor size drives prognosis or not after hepatectomy remains unknown. This study aimed to investigate the prognostic impact of tumor size on long-term outcomes after hepatectomy for solitary HCC patients with cirrhosis and without macrovascular invasion. A total of 813 cirrhotic patients who underwent curative hepatectomy for solitary HCC and without macrovascular invasion between 2001 and 2014 were retrospectively studied. We set 5 cm as the tumor cut-off value. Propensity score matching (PSM) was performed to minimize the influence of potential confounders including cirrhotic severity that was histologically assessed according to the Laennec staging system. Recurrence-free survival (RFS) and overall survival (OS) were compared between the two groups before and after PSM. Overall, 464 patients had tumor size ≤ 5 cm, and 349 had tumor size > 5 cm. The 5-year RFS and OS rates were 38.3% and 61.5% in the ≤ 5 cm group, compared with 25.1% and 59.9% in the > 5 cm group. Long-term survival outcomes were significantly worse as tumor size increased. Multivariate analysis indicated that tumor size > 5 cm was an independent risk factor for tumor recurrence and long-term survival. These results were further confirmed in the PSM cohort of 235 pairs of patients. In cirrhotic patients with solitary HCC and without macrovascular invasion, tumor size may significantly affect the prognosis after curative hepatectomy.

According to the social-cognitive theory and the social-information-processing theory, individuals with conduct disorder, a persistent and repetitive pattern of problematic behavior, might have cognitive biases toward hostile facial expressions. However, according to the optimal stimulation/arousal theory, the stimulation-seeking theory and the fearlessness theory, individuals with conduct disorder might have less fear and show less response to hostile or threatening facial expressions. To reconcile the discrepancy, we examined the cognitive biases including attentional processing and working memory processing to emotional faces among adolescents with conduct disorder. 35 male adolescent delinquents with conduct disorder and 35 age-matched delinquents without conduct disorder completed a visual search task and a delayed-match-to-sample task to examine their attentional processing and working memory processing for sad, angry, happy, and fearful faces, respectively. It was found that conduct disordered individuals searched angry and fearful faces, rather than sad and happy faces, more slowly than individuals without conduct disorder. However, no difference in mnemonic processing for facial emotions was found between groups. The results indicated that male adolescent delinquents with conduct disorder showed deficits in attentional orientation to hostile and threatening faces, supporting the optimal stimulation/arousal theory, the stimulation-seeking theory and the fearlessness theory, but not the social-cognitive theory.

Parkinson's disease (PD) is the most common motor-associated neurodegenerative disease. Although the pathogenesis of PD is still wrapped in the mist, accumulating evidence indicates that mitochondrial dysfunction contributes to the onset and progression of PD. We previously reported that the lysosomal protease asparagine endopeptidase (AEP) cleaves α-synuclein in the brains of PD patients. The major product, α-synuclein 1–103, significantly promotes PD-like histological changes and motor dysfunction. However, the underlying molecular mechanisms remain unknown. Here we show that α-synuclein 1–103 fragment interacts with mitochondria and induces morphological and functional abnormalities of mitochondria. Furthermore, we investigated the protective effects of 7,8-dihydroxyflavone (7,8-DHF) on mitochondrial dysfunction induced by α-synuclein 1–103 fragment. We found that 7,8-DHF ameliorated α-synuclein 1–103-induced mitochondrial impairment and motor dysfunction. These results indicate that 7,8-DHF represents a novel oral bioactive therapeutic agent for treating PD.

PurposePrimary thymic extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT) lymphoma is a rare type of MALT lymphoma. We aim to investigate the clinicopathologic features, 18F-FDG PET/CT findings and outcomes for patients with primary thymic MALT lymphoma; to explore the correlation between metabolic parameters and immunohistochemical phenotypes.MethodsA retrospective single-center study enrolled 12 patients with primary thymic MALT lymphoma between 2010 and 2021. Nineteen 18F-FDG PET/CT scans were performed, and clinicopathologic and immunohistochemical characteristics, PET/CT imaging features, and outcomes were analyzed.ResultsThe male-to-female ratio was 1. The median age at diagnosis was 40 (range 31–68). The long diameter of the lesions ranged from 3.5 to 15.7. Histopathological examinations revealed that the normal thymic lobular architecture was effaced by a diffuse lymphoid infiltrate, but residual Hassall corpuscles could still be identified, mostly with CD20+, PAX5+, CD3-, CD23-, CD10-, BCL-6-, cyclin D1-, EBER- and low Ki-67. The gene rearrangement indicated that the IGH gene but not TCR gene was found in 7 patients. Six initial PET/CT scans showed a mean SUVmax of 6.8 (range, 3.1–12.4), a mean MTV = 40.0 (range, 6.7–81.4), and a mean TLG = 144.3 (range, 19.7–286.4). During the follow-up period, there was no death except for the patient with DLBCL who died 59 months after diagnosis of primary thymic MALT. No significant correlation between SUVmax and Ki-67 index was observed (r = 0.355, P > 0.05).ConclusionPrimary thymic MALT lymphoma should be considered in patients with multilocular cystic lesions with different degrees of 18F-FDG uptake in the anterior mediastinum. The results of this study showed no correlation between SUVmax and Ki-67 index.

The efficient removal of organic contaminants from wastewater is, nowadays, a prominent area of study due to its biological as well as environmental significance. Antibiotics are now found in wastewater because of their high use, which has become a source of aquatic pollution. These antibiotics have dangerous implications for people’s health. Hence, effective pharmaceutical removal from wastewater and contaminated water bodies, especially the removal of antibiotics, is of major interest to global research organizations. This is why it is necessary to investigate this class of toxic material in wastewater discharge. We synthesized three different coordination polymers (CPs) in the presence of various assistant carboxylate linkers, namely, [Zn(Hbtc)(dip)]n (1), [Zn4(1,2-bdc)4(dip)4]n (2), and [Zn(1,4-bdc)(dip)]n (3) (3,5-di(1H-imidazol-1-yl)pyridine = dip, 1,3,5-benzenetricarboxylic acid = H3btc, 1,2-benzenedicarboxylic acid = 1,2-H2bdc, and 1,4-benzendicarboxylic acid = 1,4-bdc). These CPs were characterized by using different techniques, including single-crystal X-ray diffraction. The structural studies demonstrated that in 2, there are four Zn(II) centers and both centers are in different coordination environments (Zn2 has distorted tetrahedral geometry, whereas Zn1, Zn3, and Zn4 have square pyramidal geometry). Hirshfeld surfaces analysis revealed that different types of intermolecular interactions (C⋯C, H⋯C, H⋯H, O⋯C, N⋯H, and O⋯H) are present in the synthesized CPs. We examined the different antibiotics, such as metronidazole (MDZ), nitrofurazone (NFZ), dimetridazole (DTZ), sulfasalazine(SLA), and oxytetracycline (OXY), degradation behaviors of the synthesized CPs, which showed remarkable degradation efficiency. 1 showed photocatalytic behavior toward the NFZ antibiotic in an aqueous media. This study also showed that these catalysts are stable and reusable under mild conditions.

Machine learning (ML) has transformed neuroimaging research by enabling accurate predictions and feature extraction from large datasets. In this study, we investigate the application of six ML algorithms (Lasso, relevance vector regression, support vector regression, extreme gradient boosting, category boost, and multilayer perceptron) to predict brain age for middle-aged and older adults, which is a crucial area of research in neuroimaging. Despite the plethora of proposed ML models, there is no clear consensus on how to achieve better performance in brain age prediction for this population. Our study stands out by evaluating the impact of both ML algorithms and image modalities on brain age prediction performance using a large cohort of cognitively normal adults aged 44.6 to 82.3 years old (N = 27,842) with six image modalities. We found that the predictive performance of brain age is more reliant on the image modalities used than the ML algorithms employed. Specifically, our study highlights the superior performance of T1-weighted MRI and diffusion-weighted imaging and demonstrates that multi-modality-based brain age prediction significantly enhances performance compared to unimodality. Moreover, we identified Lasso as the most accurate ML algorithm for predicting brain age, achieving the lowest mean absolute error in both single-modality and multi-modality predictions. Additionally, Lasso also ranked highest in a comprehensive evaluation of the relationship between BrainAGE and the five frequently mentioned BrainAGE-related factors. Notably, our study also shows that ensemble learning outperforms Lasso when computational efficiency is not a concern. Overall, our study provides valuable insights into the development of accurate and reliable brain age prediction models for middle-aged and older adults, with significant implications for clinical practice and neuroimaging research. Our findings highlight the importance of image modality selection and emphasize Lasso as a promising ML algorithm for brain age prediction.

Pyrite is widely distributed in the Longmaxi marine shale in the Upper Yangtze area of China. Pyrite, one of the important components of shale, has an important influence on the enrichment of shale gas. However, there are currently only a few studies on this topic. Based on shale samples from drilling cores using field emission scanning electron microscopy, the pore characteristics of pyrite from the Longmaxi Formation in the Upper Yangtze area of China are studied. The results showed that the intergranular pores of pyrite and abundant organic pores in the organic matter pyrite assemblages are developed in the Longmaxi Formation shale in the study area. Most pyrite framboid pores have triangular or irregular quadrilateral shapes, with pore diameters ranging from 0 to 240 nm. Pores with diameters of 80–240 nm are the major reservoir spaces for shale gas within the pyrite framboids. The average contribution rate of pyrite framboids to shale pores reaches 3.21%, and the highest contribution is 5.66%, indicating that the pyrite pores may have a favorable contribution to the shale reservoir pore system, but the contribution degree is low.

CD19-directed chimeric antigen receptor-T (CAR-T) cells with a 4-1BB or CD28 co-stimulatory domain have shown impressive antitumor activity against relapsed or refractory B cell acute lymphoblastic leukemia (r/r B-ALL). However, a parallel comparison of their performances in r/r B-ALL therapy has not been sufficiently reported. Here, we manufactured 4-1BB- and CD28-based CD19 CAR-T cells using the same process technology and evaluated their efficacy and safety in r/r B-ALL therapy based on pre-clinical and exploratory clinical investigations. In B-ALL-bearing mice, a similar antitumor effect and CAR-T kinetics in peripheral blood were observed at the CAR-T dose of 1 × 107/mouse. However, when the dose was decreased to 1 × 106/mouse, 4-1BB CAR-T cells were more potent in eradicating tumor cells and showed longer persistence than CD28 CAR-T cells. Retrospective analysis of an exploratory clinical study that used 4-1BB- or CD28-based CAR-T cells to treat r/r B-ALL was performed. Compared with CD28 CAR-T cells, 4-1BB CAR-T cells resulted in higher antitumor efficacy and less severe adverse events. This study demonstrated that the performance of 4-1BB CAR-T cells was superior to that of CD28 CAR-T cells in suppressing CD19+ B-ALL, at least under our manufacturing process.

Abstract Triggering receptor expressed on myeloid cells 2 (TREM2) is a receptor mainly expressed on the surface of microglia. It mediates multiple pathophysiological processes in various diseases. Recently, TREM2 has been found to play a role in the development of Alzheimer’s disease (AD). TREM2 is a transmembrane protein that is specifically expressed on microglia in the brain. It contains a long ectodomain that directly interacts with the extracellular environment to regulate microglial function. The ectodomain of TREM2 is processed by a disintegrin and metalloprotease, resulting in the release of a soluble form of TREM2 (sTREM2). Recent studies have demonstrated that sTREM2 is a bioactive molecule capable of binding ligands, activating microglia, and regulating immune responses during the AD continuum. Clinical studies revealed that sTREM2 level is elevated in cerebrospinal fluid (CSF) of AD patients, and the sTREM2 level is positively correlated with the levels of classical CSF biomarkers, namely t-tau and p-tau, indicating that it is a reliable predictor of the early stages of AD. Herein, we summarize the key results on the generation, structure, and function of sTREM2 to provide new insights into TREM2-related mechanisms underlying AD pathogenesis and to promote the development of TREM2-based therapeutic strategy.