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Mao Mu,1,* Shi Zuo,2,* Rong-Min Wu,3 Kai-Sheng Deng,1 Shuang Lu,1 Juan-Juan Zhu,1 Gao-Liang Zou,1 Jing Yang,1 Ming-Liang Cheng,1 Xue-Ke Zhao1 1Department of Infectious Diseases, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; 2Department of Hepatobiliary Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, China; 3Department of Ultrasonography, The Maternity Hospital of Guizhou, Guiyang, Guizhou, China *These authors contributed equally to this work Purpose: Liver fibrosis is a worldwide health issue. Development of effective new drugs for treatment of this disease is of great importance. This study investigated the therapeutic effects of ferulic acid on liver fibrosis in vitro and in vivo.Materials and methods: Human hepatic stellate cell line (HSC) LX-2 was used for in vitro assays. Transforming growth factor β1 (TGF-β1) was used to induce hepatic fibrosis in LX-2 cells. Western blot was used to detect protein levels of collagen I, fibronectin, α-smooth muscle actin (SMA), p-Smad2, p-Smad3, p-p38, and p-JNK. Gene expression was measured by RT-qPCR. Fluorescence staining was used to determine localization of Smad4. CCl4-induced hepatic fibrosis in SD rats was used as an in vivo model. Histological features were detected by hematoxylin and eosin staining. Levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), hexadecenoic acid (HA), and hydroxyproline (Hyp) were measured by ELISA.Results: TGF-β1 treatment significantly increased levels of collagen I, fibronectin, α-SMA, p-Smad2, p-Smad3, and Smad4 in LX-2 cells. Ferulic acid improved TGF-β1-induced hepatic fibrosis via regulation of the TGF-β1/Smad pathway. Consistent with in vitro data, CCl4 caused severe hepatic fibrosis in SD rats, as determined by ALT, AST, HA, and Hyp upregulation. Protein levels of p-Smad2 and p-Smad3 in liver tissues were significantly increased following treatment with CCl4. All CCL4-induced changes were markedly attenuated by ferulic acid treatment.Conclusion: Ferulic acid potently improved hepatic fibrosis via inhibition of the TGF-β1/Smad pathway in vitro and in vivo. These findings provided evidence for potential use of ferulic acid to treat or prevent liver fibrosis. Keywords: ferulic acid, TGF-β1, CCl4, hepatic fibrosis, Smad signaling pathway

Mu M, Zuo S, Wu RM, et al. Drug Des Devel Ther. 2018;12:4107–4115. An error has been found in a couple of the image labels for Figure 3F. On page 4112, the original Figure 3F image appears as: Read the original article:

Hai-Fei Chen,* Bin-Xian Xu, Hong-Shi Shen,* Zheng-Yang Li, Ling-Juan Jin, Jie-Qing Tang, Jing Wang, Jing-Jing Zhu, Long-Mei Qin, Qing-Ya Cui, Yong-Ya Ren, Tian-Qin Wu Department of hematology, 100th hospital of People’s Liberation Army, Suzhou, Jiangsu province, The People’s Republic of China *These authors have contributed equally to this paper Objective: To investigate the clinical characteristics of seronegative hepatitis-associated aplastic anemia (AA) (SNHAA) and hepatitis B virus (HBV) infection complicating AA (HBVAA), and thereby compare the efficacy of immunosuppressive therapy (IST).Methods: An analysis was conducted on the clinical data of ten patients with SNHAA out of 332 cases of AA from our center at AA diagnosis, and on the efficacy of IST. This was compared to 22 cases of HBVAA at AA onset as well as the associated IST outcomes.Results: Nine patients with SNHAA developed severe aplastic anemia, with a median age of 18 years. After IST, six (60%) of the SNHAA patients achieved complete remission and two achieved partial remission. The patients with HBVAA had a total response rate of 82.3%. The disease recurred in two HBVAA patients. No statistically significant differences were observed in response rate, mortality, and recurrence rate between both groups. As compared with HBVAA, patients with SNHAA had a shorter interval from the acute episode of hepatitis to AA onset (4 months versus 92 months, P=0.00), a quicker response to IST (2.5 months versus 4.5 months, P=0.018), a lower proportion of bone marrow hematopoietic tissues (20.6% versus 23.6%, P=0.03), and lower white blood cell and absolute neutrophil count (0.8×109/L versus 1.23×109/L and 0.26×109/L versus 0.58×109/L, P=0.026 and P=0.0009, respectively). No significant liver damage or hepatitis B fulminant infection was observed in either group during the follow-up. Conclusion: The prevalence of SNHAA is 3.01%. SNHAA often presents as severe AA and responds to IST quickly. Neither hepatitis prior to AA nor AA complicating HBV infection have been shown to influence the early efficacy of IST and adverse events, and HBV may not be the causative agent of AA. Keywords: hepatitis-associated aplastic anemia, hepatitis B infection, liver injury

Hai-Fei Chen,1,2 Li-Ping Xu,1 Zhi-Yong Luo,1 Zi-Qiang Yu,2 Zheng-Yang Li,1 Qing-Ya Cui,1 Long-Mei Qin,1 Yong-Ya Ren,1 Hong-Shi Shen,1 Jie-Qing Tang,1 Ling-Juan Jin,1 Jing-Jing Zhu,1 Jing Wang,1 Ke-Yuan Wang,1 Tian-Qin Wu,1 Zhao-Yue Wang21Department of Hematology, 100th Hospital of People's Liberation Army, 2Jiangsu Institute of Hematology, First Affiliated Hospital of Soochow University, Suzhou, People's Republic of ChinaAbstract: A 41-year-old male had suffered from gradual hearing loss in his right ear for 2 years. Head computed tomography and magnetic resonance imaging scans showed a neoplasm in the cerebellopontine angle region, which was confirmed by the diagnosis of acoustic neurilemmoma by pathological findings after surgery. Following surgery, he routinely received valproic acid (VPA) to prevent seizures. However, the patient presented with hypofibrinogenemia and cerebral hemorrhage after taking VPA for 12 days. The hypofibrinogenemia recurred when VPA was re-administered. After withdrawal of VPA, his fibrinogen concentration rose to normal within several days. As far as we are aware, this is the first case of cerebral hemorrhage due to VPA to have been reported. Herein, as well as reporting on this case, a mini review of the relevant literature is also presented.Keywords: side effect, hypofibrinogenemia, cerebral hemorrhage, cerebellopontine angle, neoplasm

Although pretransplant diabetes is a risk factor for mortality post-liver transplant, the underlying mechanism has not been fully defined. In a murine liver partial warm ischemia model, we addressed the question of how diabetes/hyperglycemia impacted tissue inflammatory injuries against ischemia reperfusion (IR), focusing on the advanced glycation endproduct (AGE) and its receptor (RAGE) pathway. Our results showed that hepatocellular injury was exacerbated in streptozotocin-induced diabetic mice against IR, in association with hyper-inflammatory immune activation in livers. Serum levels of AGEs, but not HMGB1, were increased in diabetic mice in response to liver IR. Both RAGE antagonist peptides and small interfering RNA alleviated liver injuries and inhibited inflammatory immune activation against IR in diabetic, but not normal, mice. Kupffer cells (KCs)/macrophages, but not hepatocytes, from diabetic mice expressed significantly higher levels of RAGE, leading to their hyper-inflammatory responsiveness to both TLR ligands and AGEs. In vitro, hyperglycemia increased macrophage RAGE expression and enhanced their TLR responses. Our results demonstrated that activation of the AGE-RAGE signaling pathway in KCs was responsible for hyper-inflammatory immune responses and exacerbated hepatocellular injuries in diabetic/hyperglycemic hosts against liver IR.

A 52-year-old female was treated with CT-guided stereotactic aspiration for acute spontaneous pontine hemorrhage. On postoperative day 7, the patient was complicated by Acinetobacter baumannii sepsis. As sepsis was stabilized, she developed flaccid weakness and autonomic dysfunction on postoperative day 21. Investigations including neurophysiological studies and cerebral spinal fluid analysis prompted the diagnosis of acute motor axonal neuropathy, a variant of Guillain-Barré syndrome. Intravenous administration of immunoglobulin resolved her potentially life-threatening autonomic instability. At 1-year follow-up, she was able to stand with significant assistance. Although Guillain-Barré syndrome rarely occurs, clinicians should be alert to the possibility of this potentially life-threatening consequence after cranial surgery with severe respiratory infection. [ABSTRACT FROM AUTHOR]

Electrochemical imaging enables an in-depth analysis of the interface heterogeneity and reaction kinetics of single entities. However, electrode passivation during electrochemical reactions decreases the active sites and harms the long-term stability. Here, we introduce a method using laser-induced photothermal effects to restore the electrochemical activity, which is particularly displayed as enhanced micrometric patterns in electrochemiluminescence (ECL) microscopy. By co-localization characterization and X-ray photoelectron spectroscopy, the mechanism of active site regeneration is validated as the removal of the oxide film for restoring the local surface ECL reactivity under laser irradiation. The surface-confined and voltage-dependent features of ECL allows for easy pattern erasure and rewriting, and it shows good reversibility and anti-counterfeiting potential. This approach overcomes the passivation processes, evidently improves the image quality of single biological entities including Shewanella bacteria and cells, and makes the subtle contour structures more distinct. The renewable electrode interface also enhances the ECL signal of model bead-based bioassays. This approach not only showcases precise control in fabricating micron patterns but also holds promise for enhancing the sensitivity in electrochemical immunoassays and bioimaging., (© 2024 Wiley‐VCH GmbH.)

In this study, tungsten oxide nanosheets loaded with nitrogen-doped graphene oxide quantum dots (NGQDs/WO 3 NSs) were fabricated as SERS substrates. The promoted photo-induced charge transfer (PICT) and the strong π-π stacking effect resulting from the unique structure of the NGQDs contributed to the enhanced SERS signal.

The sewer system, despite being a significant source of methane emissions, has often been overlooked in current greenhouse gas inventories due to the limited availability of quantitative data. Direct monitoring in sewers can be expensive or biased due to access limitations and internal heterogeneity of sewer networks. Fortunately, since methane is almost exclusively biogenic in sewers, we demonstrate in this study that the methanogenic potential can be estimated using known sewer microbiome data. By combining data mining techniques and bioinformatics databases, we developed the first data-driven method to analyze methanogenic potentials using a data set containing 633 observations of 53 variables obtained from literature mining. The methanogenic potential in the sewer sediment was around 250-870% higher than that in the wet biofilm on the pipe and sewage water. Additionally, k -means clustering and principal component analysis linked higher methane emission rates (9.72 ± 51.3 kg CO 2  eq m -3 d -1 ) with smaller pipe size, higher water level, and higher potentials of sulfate reduction in the wetted pipe biofilm. These findings exhibit the possibility of connecting microbiome data with biogenic greenhouse gases, further offering insights into new approaches for understanding greenhouse gas emissions from understudied sources.

The global transition to net-zero emissions necessitates the integration of clean hydrogen as a key solution. To facilitate the required expansion of clean hydrogen production, sustainable water sources are required to support the electrolysis process. Utilizing nontraditional water sources such as water resource recovery facility (WRRF) effluents could potentially alleviate the water constraints and create cobenefits, but the real-world feasibility has not been explored in depth. Here, we investigated the geospatial interplay between WRRFs and H 2 users in a clean hydrogen economy. We developed an optimization framework for contiguous U.S. that would identify H 2 users-WRRF pairing through techno-economic constraint and multicriteria decision analysis, and we found that utilizing reclaimed water from WRRFs could save 66% (62-99%) of freshwater for clean hydrogen economy while accumulating $758 (275-1162) million annual national cost savings. The added benefits from H 2 users to WRRFs such as pure oxygen aeration would provide a compelling new opportunity for infrastructural symbiosis but warrant a future investigation on its technical and economic feasibilities.

Anaplasma phagocytophilum ( A. phagocytophilum ) is an emerging zoonotic pathogen causing human granulocytic anaplasmosis, linked to small mammal reservoirs that harbor various zoonotic pathogens, underscoring their importance in public health and ecology. This study seeks to determine the prevalence of A. phagocytophilum in small mammals using PCR, then sequence and genotype positive samples, and assess infection risk factors. Small mammals were seasonally captured and a nested polymerase chain reaction (nested-PCR) was conducted targeting the 16S rRNA gene on spleen samples to detect A. phagocytophilum infection from three counties in western Yunnan province, China. Positive samples were sequenced and genotyped, revealing genetic diversity and regional clustering of the pathogen. A total of 1,605 small mammals belonging to 30 species, 18 genera, 6 families, 3 orders were captured seasonally and screened in this region, yielding a 0.93% infection rate with A. phagocytophilum (15/1605). Significant variations in infection rates were observed across different species, counties, and habitats. The 16Sr RNA genes of A. phagocytophilum were categorized into two distinct clades, indicating notable genetic diversity. The identification of genetic variants in spleen samples underscores the potential public health risk and the critical importance of the One Health approach in disease surveillance. Our findings emphasize the necessity for continuous monitoring and highlight the value of nested-PCR testing on spleen samples for accurate prevalence assessment., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Zhu, Zhang, Hong, Yu, Hong, Liu, Li and Yin.)

The fabrication of high-performance microbial fuel cells requires the evaluation of the activity of electrochemically active bacteria. However, this is challenging because of the time-consuming nature of biofilm formation and the invasive nature of labeling. To address this issue, we developed a fast, label-free, single-cell Raman spectroscopic method. This method involves investigating the "pure" linear Stark effect of endogenous CO in the silent region of biological samples, which allows for probing the intrinsic electric field in the outer-membrane cytochromes of live bacterial cells. We found that reduced outer-membrane cytochromes can generate an additional intrinsic electric field equivalent to an applied potential of +0.29 V. We also found that the higher the electrical activity of the cell, the larger the generated electric field. This was also reflected in the output current of the constructed microbial fuel cells. Raman spectroscopy was employed to facilitate the assessment of electrochemical activity at the single-cell level in highly-diluted bacterial samples. After analysis, inactive bacteria were ablated by laser heating, and 20 active cells were cultured for further testing. The rapid and high-throughput probing of the intrinsic electric field offers a promising platform for high-efficiency screening of electrochemically active bacterial cells for bioenergetic and photosynthetic research., (© 2024 Wiley-VCH GmbH.)

Background: Glucagon-like peptide-1 receptor agonists (GLP-1RA) and sodium-glucose co-transporter-2 inhibitors (SGLT-2I) are associated with significant cardiovascular benefit in type 2 diabetes (T2D). However, GLP-1RA or SGLT-2I alone may not improve some cardiovascular outcomes in patients with prior cardiovascular co-morbidities., Aim: To explore whether combining GLP-1RA and SGLT-2I can achieve additional benefit in preventing cardiovascular diseases in T2D., Methods: The systematic review was conducted according to PRISMA recommendations. The protocol was registered on PROSPERO (ID: 42022385007). A total of 107049 participants from eligible cardiovascular outcomes trials of GLP-1RA and SGLT-2I were included in network meta-regressions to estimate cardiovascular benefit of the combination treatment. Effect modification of prior myocardial infarction (MI) and heart failure (HF) was also explored to provide clinical insight as to when the combination treatment should be considered., Results: The estimated hazard ratios (HR) GLP-1RA/SGLT-2I vs Placebo (0.75-0.98) and HR Combination vs GLP-1RA/SGLT-2I (0.26-0.86) for primary and secondary cardiovascular outcomes suggested that the combination treatment may achieve additional cardiovascular benefit compared with GLP-1RA or SGLT-2I alone. In patients with prior MI or HF, the mono-therapies may not improve the overall cardiovascular outcomes, as the estimated HR MI+/HF+ (0.57-1.52) suggested that GLP-1RA or SGLT-2I alone may be associated with lower risks of hospitalization for HF but not cardiovascular death., Conclusion: Considering its greater cardiovascular benefit in T2D, the combination treatment of GLP-1RA and SGLT-2I might be prioritized in patients with prior MI or HF, where the monotherapies may not provide sufficient cardiovascular protection., Competing Interests: Conflict-of-interest statement: Zhu JJ and Gu XS have no conflict of interest or financial disclosures that are relevant to the content of this research report. Wilding JPH reports consultancy/advisory board work for the pharmaceutical industry contracted via the University of Liverpool (no personal payment) for Altimmune, AstraZeneca, Boehringer Ingelheim, Cytoki, Lilly, Napp, Novo Nordisk, Menarini, Pfizer, Rhythm Pharmaceuticals, Sanofi, Saniona, Tern, and Shionogi & Ysopia; research grants for clinical trials from AstraZeneca and Novo Nordisk and personal honoraria/lecture fees from AstraZeneca, Boehringer Ingelheim, Medscape, Napp, Novo Nordisk, and Rhythm. Wilding JPH is past president of the World Obesity Federation, a member of the Association for the Study of Obesity, Diabetes UK, EASD, ADA, Society for Endocrinology, and the Rank Prize Funds Nutrition Committee. Wilding JPH is national lead for the Metabolic and Endocrine Speciality Group of the UK NIHR Clinical Research Network., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

Proteolysis-targeting chimeras (PROTACs) have accelerated drug development; however, some challenges still exist owing to their lack of tumor selectivity and on-demand protein degradation. Here, we developed a miRNA-initiated assembled pre-PROTAC (miRiaTAC) platform that enables the on-demand activation and termination of target degradation in a cell type-specific manner. Using miRNA-21 as a model, we engineered DNA hairpins labeled with JQ-1 and pomalidomide and facilitated the modular assembly of DNA-encoded pre-PROTACs through a hybridization chain reaction. This configuration promoted the selective polyubiquitination and degradation of BRD4 upon miR-21 initiation, highlighting significant tumor selectivity and minimal systemic toxicity. Furthermore, the platform incorporates photolabile groups, enabling the precise optical control of pre-PROTACs during DNA assembly/disassembly, mitigating the risk of excessive protein degradation. Additionally, by introducing a secondary ligand targeting CDK6, these pre-PROTACs were used as a modular scaffold for the programmable assembly of active miRiaTACs containing two different warheads in exact stoichiometry, enabling orthogonal multitarget degradation. The integration of near-infrared light-mediated photodynamic therapy through an upconversion nanosystem further enhanced the efficacy of the platform with potent in vivo anticancer activity. We anticipate that miRiaTAC represents a significant intersection between dynamic DNA nanotechnology and PROTAC, potentially expanding the versatility of PROTAC toolkit for cancer therapy., (© 2024 Wiley-VCH GmbH.)

Objective: To analyze the short-term clinical efficacy and safety of arsenic trioxide (ATO) combined with a modified N7 induction regimen in the treatment of children with high-risk neuroblastoma (NB). Methods: This study was a prospective, single-arm, multicenter phase Ⅱ clinical study. Sixty-seven high-risk NB children from eight units of Sun Yat-sen Memorial Hospital of Sun Yat-sen University, Wuhan Children's Hospital of Tongji Medical College of Huazhong University of Science and Technology, First Affiliated Hospital of Guangxi Medical University, Hainan General Hospital, Affiliated Hospital of Guangdong Medical University, Kunming Children's Hospital, Tongji Hospital of Tongji Medical College of Huazhong University of Science and Technology, and Guangdong Provincial Agricultural Reclamation Center Hospital were enrolled from January 2019 to August 2023 and were treated with ATO combined with a modified N7 induction regimen. The efficacy and adverse effects at the end of induction chemotherapy were assessed and analyzed, and the differences in the clinical characteristics were further compared between the treatment-responsive and treatment-unresponsive groups by using the Fisher's exact test. Results: Among 67 high-risk NB children, there were 40 males (60%) and 27 females (40%), with the age of disease onset of 3.5 (2.6, 4.8) years. Primary NB sites were mostly in retroperitoneum (including adrenal gland) (56/67, 84%) and the common metastases sites at initial diagnosis were distant lymph node in 25 cases (37%),bone in 48 cases (72%),bone marrow in 56 cases (84%) and intracalvarium in 3 cases (4%). MYCN gene amplification were detected in 28 cases (42%). At the end of induction, 33 cases (49%) achieved complete remission, 29 cases (43%) achieved partial remission, 1 case (1%) with stable disease, and 4 cases (6%) were assessed as progressive disease (PD). The objective remission rate was 93% (62/67) and the disease control rate was 94% (63/67). The percentage of central system metastases at the initial diagnosis was higher in the treatment-unresponsive group than in the treatment-responsive group (2/5 vs. 2% (1/62), P =0.013), whereas the difference in MYCN gene amplification was not statistically significant between two groups (3/5 vs. 40% (25/62), P =0.786). Grade Ⅲ or higher adverse reactions during the induction chemotherapy period were myelosuppression occurred in 60 cases (90%), gastrointestinal symptoms occurred in 33 cases (49%), infections occurred in 20 cases (30%), hepatotoxicity occurred in 4 cases (6%), and cardiovascular toxicity occurred in 1 case (2%). There were no chemotherapy-related deaths. Conclusion: ATO combined with N7-modified induction regimen had a superiority in efficacy and safety, which deserved further promotion in clinical practice.

Strategies based on nanomaterials for sterilization address the problem of antibiotic resistance faced by conventional antimicrobials, with the contribution of photocatalytic compounds being particularly prominent. Herein, to integrate multiple bactericidal techniques into a system for generating synergistic antibacterial effects, a novel photo-triggered AuAg@g-C 3 N 4 composite nanoplatform was constructed by anchoring AuAg on the surface of a g-C 3 N 4 layer. As the composite nanoplatform had a lower bandgap and superior visible light utilization efficiency, it could facilitate free electron transfer better and exhibit superior photocatalytic activity under light conditions. Moreover, the AuAg@g-C 3 N 4 composite nanoplatform integrated the bactericidal modes of silver ion toxicity, physical disruption of bacterial cell membranes by the multilayer structure, and excellent photocatalytic activity, exhibiting extremely superior bactericidal effects against Escherichia coli , Staphylococcus aureus , Pseudomonas aeruginosa and Bacillus subtilis , with a bactericidal efficiency of up to 100%.

Increasing the carbon sink capacity of terrestrial ecosystems is a primary strategy to mitigate climate change and achieve the "carbon neutrality" goal. Clarifying the status and future dynamics of carbon sink of terrestrial ecosystems in Northeast China is crucial for achieving "carbon neutrality" as this region is a core contributor to carbon sink in China's terrestrial ecosystems. Here, we systematically summarized current research on carbon sink of terrestrial ecosystems across Northeast China, including the measurements and spatial-temporal patterns of carbon sinks, driving mechanisms of carbon sinks, the assessments of carbon sink potential, and technologies for increasing carbon sequestration. There are substantial uncertainties in quantifying terrestrial ecosystem carbon sink in Northeast China due to differences in data sources and methods, especially for forest carbon sink measurements, ranging from 0.020 to 0.157 Pg C·a -1 . Carbon sink function depends on carbon exchange processes across plant-soil-atmosphere interfaces. The key pathways to enhance carbon sequestration in Northeast China under different temporal and spatial scales remains unclear. Improving terrestrial ecosystem quality is the key and core of carbon sequestration and sink enhancement. However, there is an urgent need to develop a multi-ecosystem collaborative carbon sequestration and sink enhancement technology system for the "dual carbon" goal. Future research needs to develop an accurate carbon sink measurement system that integrates multi-source data and multi-scale technologies to accurately assess the function and potential of carbon sink in Northeast China, focus on the multi-scale driving mechanism of carbon sink functions, develop new technical systems for coordinated enhancement of carbon sink for the Northeast terrestrial ecosystems, and carry out demonstrations of carbon sink enhancement technologies. These efforts will provide the scientific and technological supports for achieving the "carbon neutrality" goal.

The widespread utilization of fossil fuels has emitted large amounts of CO 2 into the atmosphere since the Industrial Revolution, leading to climate warming and frequent occurrence of extreme climate events. To effectively alleviate climate change, the international community has made various efforts to reduce carbon emissions and eliminate CO 2 from the atmosphere. In 2020, the Chinese government announced that carbon emission peaking and carbon neutrality will be achieved by 2030 and 2060, respectively. According to the current forecast, by the time carbon neutrality is achieved in 2060, even under the minimum conditions of fossil energy use, production, and living emissions, China will still have to emit about 1/4 of the current total emissions. These carbon must primarily be absorbed by ecosystems. Furthermore, approximately 140 ppm increase in CO 2 in the atmosphere since the Industrial Revolution still needs to be removed by ecosystems. Forests are the main component of terrestrial ecosystems, contributing more than 80% of the carbon sequestration capacity of all terrestrial ecosystems. However, due to the long periodicity, complexity and dynamic variability of forests, the basic concepts of ecosystem carbon sink and its time effect are still unclear, leading to problems, such as lacking technologies for improving carbon sink capacity and disorganized rules in the carbon sink trading market. In this review, we introduced carbon sink concept according to the processes of absorbing and fixing CO 2 by plant photosynthesis in forest ecosystems. Then, we analyzed the processes of time-scale-dependent carbon sinks of forest ecosystems, discussed the time effects of forest carbon sinks, and suggested using "t-year" as the unit of carbon sink (taking 3-6 months as the minimum measurement time, i.e ., the beginning of carbon sequestration). Third, we proposed the approaches to improve the carbon sink capacity of forest ecosystems. One way is to improve the carbon sink capacity (expanding forest area, improving forest quality, and increasing forest soil carbon storage) of forest ecosystems. Another approach is to maintain the carbon sink of forest ecosystems as long as possible, i.e ., to reduce temporary carbon sink (definition: carbon in the forest ecosystems emit into the atmosphere for a certain period) and to increase persistent carbon sink (definition: carbon in the forest ecosystems no longer emit into the atmosphere for a certain period; according to the relevant provisions of the Paris Agreement, the upper time limit for carbon sink measurement can be considered to be the year 2100. In order to maintain the persistent carbon sink, strateges such as efficient use of wood products (replace steel, cement, plastic with wood), control of forest fires or other disturbances-induced emissions, and turning forest biomass into biochar should be taken. Finally, we proposed to develop climate-smart forestry driven by artificial intelligence (AI), which would provide new theoretical and technical support for improving the carbon sink of forest ecosystems and facilitating sustainable forest management.

Background: Adjacent segment disease (ASD) after fusion surgery is frequently manifests as a cranial segment instability, disc herniation, spinal canal stenosis, spondylolisthesis or retrolisthesis. The risk factors and mechanisms of ASD have been widely discussed but never clearly defined., Aim: To investigate the risk factors and clinical significance of retrograde movement of the proximal vertebral body after lower lumbar fusion., Methods: This was a retrospective analysis of the clinical data of patients who underwent transforaminal lumbar interbody fusion surgery between September 2015 and July 2021 and who were followed up for more than 2 years. Ninety-one patients with degenerative lumbar diseases were included (22 males and 69 females), with an average age of 52.3 years (40-73 years). According to whether there was retrograde movement of the adjacent vertebral body on postoperative X-rays, the patients were divided into retrograde and nonretrograde groups. The sagittal parameters of the spine and pelvis were evaluated before surgery, after surgery, and at the final follow-up. At the same time, the Oswestry Disability Index (ODI) and Visual Analogue Scale (VAS) were used to evaluate the patients' quality of life., Results: Nineteen patients (20.9%) who experienced retrograde movement of proximal adjacent segments were included in this study. The pelvic incidence (PI) of the patients in the retrograde group were significantly higher than those of the patients in the nonretrograde group before surgery, after surgery and at the final follow-up ( P < 0.05). There was no significant difference in lumbar lordosis (LL) between the two groups before the operation, but LL in the retrograde group was significantly greater than that in the nonretrograde group postoperatively and at the final follow-up. No significant differences were detected in terms of the |PI-LL|, and there was no significant difference in the preoperative lordosis distribution index (LDI) between the two groups. The LDIs of the retrograde group were 68.1% ± 11.5% and 67.2% ± 11.9%, respectively, which were significantly lower than those of the nonretrograde group (75.7% ± 10.4% and 74.3% ± 9.4%, respectively) ( P < 0.05). Moreover, the patients in the retrograde group had a greater incidence of a LDI < 50% than those in the nonretrograde group ( P < 0.05). There were no significant differences in the ODI or VAS scores between the two groups before the operation, but the ODI and VAS scores in the retrograde group were significantly worse than those in the nonretrograde group after the operation and at the last follow-up, ( P < 0.05)., Conclusion: The incidence of posterior slippage after lower lumbar fusion was approximately 20.9%. The risk factors are related to a higher PI and distribution of lumbar lordosis. When a patient has a high PI and insufficient reconstruction of the lower lumbar spine, adjacent segment compensation via posterior vertebral body slippage is one of the factors that significantly affects surgical outcomes., Competing Interests: Conflict-of-interest statement: All the authors declare no conflicts of interest., (©The Author(s) 2024. Published by Baishideng Publishing Group Inc. All rights reserved.)

The reliable detection of organophosphorus pesticides (OPs) in complex matrices remains an enormous challenge due to inevitable interference of sample matrices and testing factors. To address this issue, we designed a nanozyme-coated mesoporous COF with guest molecule loading, and successfully used it to construct a dual-ratio dual-mode sensor through target-regulated signal generation. The multifunctional COF-based composite (MB/COF@MnO 2 , MCM) featured high loading of methylene blue (MB), oxidase-like MnO 2 coatings as gatekeepers, and specific recognition of thiocholine (TCh). TCh, a regulator produced from acetylcholinesterase (AChE)-catalyzed hydrolysis of acetylthiocholine, could decompose MnO 2 coatings, triggering the release of abundant MB and oxidation of few o-phenylenediamine (OPD). OPs, strong inhibitors of AChE, could restrain TCh production and MnO 2 decomposition, thereby controlling the release of less MB and oxidation of more OPD. This regulation boosted the dual-ratio dual-mode assay of OPs by using the released MB and oxidized OPD in the solution as testing signals, measured by both fluorescent and electrochemical methods. Experimental results demonstrated the sensitive detection of dichlorvos with LODs of 0.083 and 0.026 ng/mL via the fluorescent/electrochemical mode, respectively. This study represented a creative endeavor to develop dual-ratio dual-mode sensors for OPs detection in complex samples, offering high sensitivity, excellent selectivity, and good reliability., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Arterial endothelial cells (AECs) are the founder cells for intraembryonic haematopoiesis. Here, we report a method for the efficient generation of human haemogenic DLL4+ AECs from pluripotent stem cells (PSC). Time-series single-cell RNA-sequencing reveals the dynamic evolution of haematopoiesis and lymphopoiesis, generating cell types with counterparts present in early human embryos, including stages marked by the pre-haematopoietic stem cell genes MECOM/EVI1, MLLT3 and SPINK2. DLL4+ AECs robustly support lymphoid differentiation, without the requirement for exogenous NOTCH ligands. Using this system, we find IL7 acts as a morphogenic factor determining the fate choice between the T and innate lymphoid lineages and also plays a role in regulating the relative expression level of RAG1. Moreover, we document a developmental pathway by which human RAG1+ lymphoid precursors give rise to the natural killer cell lineage. Our study describes an efficient method for producing lymphoid progenitors, providing insights into their endothelial and haematopoietic ontogeny, and establishing a platform to investigate the development of the human blood system., (© 2024. The Author(s).)

Objective: To investigate the topological properties of the white matter network in the drug-naive first-episode children and adolescent with obsessive-compulsive disorder (OCD). Methods: This study was a case-control study. First-episode OCD childhren and adolescents(OCD group) who were treated in the outpatient or inpatient department of the Second Affiliated Hospital of Xinxiang Medical University from July 2018 to October 2023 were collected as the research subjects. Healthy controls (control group)matched by gender, age and education level were used as controls. Deterministic tractography technique was used to construct the whole brain white matter structural network, and graph theory analysis method was used to analyze the topological attributes of the whole brain white matter structure network in OCD children and adolescents. A network-based statistical method was used to examine the inter-group differences in the functional connectivity strength of the whole brain network. Results: Finally, 31 cases were included in the obsessive-compulsive disorder group, including 22 males and 9 females, with an age of (13.5±1.6) years; There were 34 cases in the control group, including 22 males and 12 females, with an age of (12.7±1.4) years. The global efficiency and local efficiency of the OCD group (0.62±0.03, 0.70±0.07) were significantly higher than those of the control group (0.50±0.06, 0.54±0.21) [both P <0.01, false discovery rate(FDR)correction]; while the characteristic path length (1.77±0.08) was significantly smaller than that of the control group (2.10±0.23) ( P <0.01, FDR correction).The centrality comparison of nodal betweenness centrality showed that in the OCD group, the connections were enhanced in the left lateral orbitofrontal gyrus, right dorsal agranular insula, left dorsal granular insula, right granular insula, right posterior central gyrus main area of parietal lobe, left ventral granular insula, granular insula, left ventral granulosa, left granular insula, and left dorsal agranular insula [all P <0.001, family wise error (FWE) correction], while the connection of right thalamic was weakened ( P <0.001, FWE correction), There were sub-networks characterized by significantly enhanced connection strength of relevant nodes in subcortical, visual network, and default mode network ( P <0.05, permutation test 5 000 times). Conclusions: The topological properties of the brain's functional network in children and adolescents with OCD exhibit abnormalities, indicating an immature state of brain functional connectivity.

C-C coupling is of utmost importance in the electrocatalytic reduction of CO 2 , as it governs the selectivity of diverse product formation. Nevertheless, the difficulties to directly observe C-C coupling pathways at a specific nanocavity hinder the advances in catalysts and electrolyzer design for efficient high-value hydrocarbon production. Here we develop a nano-confined Raman technology to elucidate the influence of the local electric field on the evolution of C-C coupling intermediates. Through precise adjustments to the Debye length in nanocavities of a copper catalyst, the overlapping of electrical double layers drives a transition in the C-C coupling pathway at a specific nanocavity from *CHO-*CO coupling to the direct dimerization of *CO species. Experimental evidence and simulations validate that a reduced potential drop across the compact layer promotes a higher yield of CO and promotes the direct dimerization of *CO species. Our findings provide insights for the development of highly selective catalyst materials tailored to promote specific products., (© 2024. The Author(s).)

A facile cation modulation strategy is proposed for the synthesis of copper/cobalt bimetallic sulfides dispersed on hierarchical carbon nanoflowers, which exhibit excellent oxygen electrocatalysis capacity to drive electrochemiluminescence for cytosensing.

HER2-positive and triple-negative breast cancers (TNBC) are difficult to treat and associated with poor prognosis. Despite showing initial response, HER2-positive breast cancers often acquire resistance to HER2-targeted therapies, and TNBC lack effective therapies. To overcome these clinical challenges, we evaluated the therapeutic utility of co-targeting TrkA and JAK2/STAT3 pathways in these breast cancer subtypes. Here, we report the novel combination of FDA-approved TrkA inhibitors (Entrectinib or Larotrectinib) and JAK2 inhibitors (Pacritinib or Ruxolitinib) synergistically inhibited in vitro growth of HER2-positive breast cancer cells and TNBC cells. The Entrectinib-Pacritinib combination inhibited the breast cancer stem cell subpopulation, reduced expression of stemness genes, SOX2 and MYC, and induced apoptosis. The Entrectinib-Pacritinib combination suppressed orthotopic growth of HER2-positive Trastuzumab-refractory breast cancer xenografts and basal patient-derived xenograft (PDXs), reduced tumoral SOX2 and MYC, and induced apoptosis in both mouse models. The Entrectinib-Pacritinib combination inhibited overall metastatic burden, and brain and bone metastases of intracardially inoculated TNBC cells without toxicity. Together, our results demonstrate for the first time that co-inhibition of TrkA and JAK2 synergistically suppresses breast cancer growth and metastasis, thereby providing preclinical evidence that supports future clinical evaluations., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Objective: To assess the clinical features and effectiveness of antiviral therapy in newborns with sensorineural hearing loss (SNHL) caused by congenital congenital cytomegalovirus (cCMV) infection, and to speculate the risk factors for poor hearing outcomes. Methods: A multicenter prospective cohort study wasconducted, enrolling 176 newborns diagnosed with cCMV at four research centers in Zhejiang Province from March 1, 2021, to April 30, 2024. Clinical characteristics at birth were recorded and hearing was followed up. The children were divided into groups based on their condition at birth, specifically into asymptomatic, mild symptom, and moderate to severe symptom groups. Additionally, they were divided into SNHL and normal hearing groups based on the results of air conduction brainstem audiometry at birth. And they were also divided into treatment and untreated groups according to antiviral treatment. Mann Whitney U test, and chi square test were used for inter group comparison to analyze the differences in clinical features between different disease groups, and to analyze the effects of clinical features, antiviral therapy, and other factors on hearing improvement. Logistic regression analysis was employed to identify the risk factors influencing hearing outcomes. Results: Among the cohort of 176 children diagnosed infection with cCMV, 90 cases were male and 86 cases were female. Of these, 79 cases were asymptomatic, 12 cases classified as mild cCMV and 85 cases as moderate to severe cCMV. Fifty cases belonged to SNHL group, with different degrees of severity, including 30 cases of mild, 9 cases of moderate, 5 cases of severe, and 6 cases of extremely severe SNHL. Among the 121 cases in the normal hearing group, 2 cases (1.7%) exhibited late-onset hearing loss despite having normal hearing at birth. Among 81 cases (46.0%) who completed the hearing follow-up, 71 cases (87.7%) had good hearing outcomes and 10 cases (12.3%) had poor hearing outcomes. Among the 81 children, 29 cases (35.8%) had SNHL at birth. During follow-up, the hearing threshold improved in 19 cases (65.5%), remained stable in 7 cases (24.1%) and progressed in 3 cases (10.3%). A total of 26 cases in the treatment group and 55 cases in the untreated group completed the hearing follow-up assessment. The rate of hearing improvement in the treatment group was found to be higher compared to the untreated group (13 cases (50.0%) vs. 6 cases (10.9%), χ 2 =15.00, P <0.01), with individuals in the treatment group having a 4.58 times greater likelihood of experiencing hearing improvement ( RR =4.58,95% CI 1.96-10.70, P <0.05). However, no statistically significant difference was observed in hearing outcomes between the antiviral treatment group and the untreated group ( RR =0.90, 95% CI 0.57-1.41, P =0.517). Multivariate analysis further confirmed SNHL ( OR =11.58, 95% CI 2.10-63.93, P =0.005) and preterm birth ( OR =4.98, 95% CI 1.06-23.41, P =0.042) as independent risk factors for poor hearing outcomes. Conclusions: SNHL resulting from cCMV infection presents symptoms at birth and can be improved by antiviral therapy. Poor hearing outcomes are associated with SNHL and prematurity.

Biting flies, including stable flies and horn flies, are considered important pests of livestock, companion animals, and humans by inflicting painful bites and interrupting normal animal behavior and human recreational/outdoor activities. It is estimated that they cause an annual loss of over 3 billion dollars in the US livestock industry. Both groups of pest flies further transmit various infectious diseases to animals and humans. The present review summarizes recent research advancements in stable and horn fly chemical and sensory ecology, especially in the discovery of novel attractants and repellents, as well as their controls for these blood-sucking flies and beyond., Competing Interests: Declaration of Competing Interest The authors declare that they have no competing interest., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Cardiac myosin-binding protein C (cMyBP-C) is a novel cardiac marker of acute myocardial infarction (AMI) and acute cardiac injuries (ACI). Construction of point-of-care testing techniques capable of sensing cMyBP-C with high sensitivity and precision is urgently needed. Herein, we synthesized an Au@NGQDs@Au/Ag multi-shell nanoUrchins (MSNUs), and then applied it in a colorimetric/SERS dual-mode immunoassay for detection of cMyBP-C. The MSNUs displayed superior stability, colorimetric brightness, and SERS enhancement ability with an enhanced factor of 5.4 × 10 9 , which were beneficial to improve the detection capability of test strips. The developed MSNU-based test strips can achieve an ultrasensitive immunochromatographic assay of cMyBP-C in both colorimetric and SERS modes with the limits of detection as low as 19.3 and 0.77 pg/mL, respectively. Strikingly, this strip was successfully applied to analyze actual plasma samples with significantly better sensitivity, negative predictive value, and accuracy than commercially available gold test strips. Notably, this method possessed a wide range of application scenarios via combining with a color recognizer application named Color Grab on the smartphone, which can meet various needs of different users. Overall, our MSNU-based test strip as a mobile health monitoring tool shows excellent sensitivity, reproducibility, and rapid detection of the cMyBP-C, which holds great potential for the early clinic diagnosis of AMI and ACI.

Pregnancy requires metabolic adaptations in order to meet support fetal growth with nutrient availability. In this study, the influence of pregnancy on metabolically active organs (adipose tissues in particular) was investigated. Our results showed that maternal weight and adipose mass presented dynamic remodeling in the periparturient mice. Meanwhile, pregnancy mice displayed obvious glucose intolerance and insulin resistance in late pregnancy as compared to non-pregnancy, which were partially reversed at parturition. Further analyses revealed that different fat depots exhibited site-specific adaptions of morphology and functionality as pregnancy advanced. Brown and inguinal white adipose tissue (BAT and IngWAT) exhibited obviously decreased thermogenic activity; by contrast, gonadal white adipose tissue (GonWAT) displayed remarkably increased lipid mobilization. Notably, we found that mammary gland differentiation was enhanced in IngWAT, followed by BAT but not in GonWAT. These result indicated that brown and white adipose tissues might synergistically play a crucial role in maintaining the maximum of energy supply for mother and fetus, which facilitates the mammary duct luminal epithelium development as well as the growth and development of fetus. Accompanied with adipose adaptation, however, our results revealed that the liver and pancreas also displayed significant metabolic adaptability, which together tended to trigger the risk of maternal metabolic diseases. Importantly, pregnancy-dependent obesity in our mice model resembled the disturbed metabolic phenotypes of pregnant women such as hyperglyceridemia and hypercholesterolemia. Our findings in this study could provide valuable clues for better understanding the underlying mechanisms of metabolic maladaptation and facilitate the development of the prevention and treatment of metabolic diseases.