Persistent acute kidney injury biomarkers: A systematic review and meta-analysis.

BACKGROUND: Various biomarkers reportedly predict persistent acute kidney injury (AKI) despite their varying predictive performance across clinical trials. This study aims to compare the accuracy of various biomarkers in predicting persistent AKI in different populations and regions. METHODS: In this meta-analysis, we searched for urinary C-C motif chemokine ligand 14 (CCL14), Tissue inhibitor of metalloproteinase-2&insulin-like growth factor-binding protein-7 (TIMP-2&IGFBP7), Neutrophil Gelatinase-Associated Lipocalin (NGAL), plasma Cystatin C (pCysC), Soluble urokinase plasminogen activator receptor (suPAR), Proenkephalin (PenK) and urinary dickkopf-3:urinary creatinine (uDKK3:uCr) from various databases including Medline, PubMed, Embase, and Cochrane. This was geared towards predicting persistent AKI in adults (>18 years). Hierarchically summarized subject work characteristic curves (HSROC) and diagnostic odds ratio (DOR) values were used to summarize the diagnostic accuracy of the biomarkers. Further, meta-regression and subgroup analyses were carried out to identify sources of heterogeneity as well as evaluate the best predictive biomarkers in different populations and regions. RESULTS: We screened 31 studies from 2,356 studies and assessed the diagnostic value of 7 biomarkers for persistent AKI. Overall, CCL14 had the best diagnostic efficacy with an AUC of 0.79 (95 % CI 0.75-0.82), whereas TIMP-2 & IGFBP7, NGAL, and pCysC had diagnostic efficacy of 0.75 (95 % CI 0.71-0.79),0.71 (95 % CI 0.67-0.75), and 0.7007, respectively. Due to a limited number of studies, PenK, uDKK3:uCr, and suPAR were not subjected to meta-analysis; however, relevant literature reported diagnostic efficacy above 0.70. Subgroup analyses based on population, region, biomarker detection time, AKI onset time, and AKI duration revealed that in the intensive care unit (ICU) population, the AUC of CCL14 was 0.8070, the AUC of TIMP-2 & IGFBP7 was 0.726, the AUC of pCysC was 0.72, and the AUC of NGAL was 0.7344; in the sepsis population, the AUC of CCL14 was 0.85, the AUC of TIMP-2&IGFBP7 was 0.7438, and the AUC of NGAL was 0.544; in the post-operative population, the AUC of CCL14 was 0.83-0.93, the AUC of TIMP-2&IGFBP7 was 0.71, and the AUC of pCysC was 0.683. Regional differences were observed in biomarker prediction of persistent kidney injury, with AUCs of 0.8558 for CCL14, 0.7563 for TIMP-2 & IGFBP7, and 0.7116 for NGAL in the Eurasian American population. In the sub-African population, TIMP-2 & IGFBP7 had AUCs of 0.7945, 0.7418 for CCL14, 0.7097 for NGAL, and 0.7007 for pCysC. for TIMP-2 & IGFBP7 was 0.7945, AUC for CCL14 was 0.7418, AUC for NGAL was 0.7097, and AUC for pCysC was 0.7007 in the sub-African population. Duration of biomarker detection, AKI onset, and AKI did not influence the optimal predictive performance of CCL14. Subgroup analysis and meta-regression of CCL14-related studies revealed that CCL14 is the most appropriate biomarker for predicting persistent stage 2-3 AKI, with heterogeneity stemming from sample size and AKI staging. CONCLUSION: This meta-analysis discovered CCL14 as the best biomarker to predict persistent AKI, specifically persistent stage 2-3 AKI.

The chemokine receptor type 5 inhibitor maraviroc alleviates sepsis-associated liver injury by regulating MAPK/NF-κB signaling.

Sepsis-related organ damage, as the most intractable problem in intensive care units (ICUs), receives a great deal of attention from healthcare professionals. Sepsis-associated liver injury (SALI) often leads to poor clinical outcomes due to its complex physiological mechanism. In previous studies, chemokine receptor 5 (CCR5) inhibitors were shown to exert unique anti-inflammatory effects. As the therapeutic effect of maraviroc (MVC) on SALI is still unclear, we aimed to explore whether MVC is effective in treating SALI. We established a model of SALI by cecal ligation and puncture (CLP) and intraperitoneally injected 20 mg/kg MVC 2 h after CLP. The results showed that MVC could significantly ameliorate liver injury after CLP. Furthermore, we demonstrated that MVC reduced inflammatory infiltration and apoptosis after SALI. In addition, we found that the function of MVC in reducing inflammation was obtained through the inhibition of the two inflammatory signaling pathways mentioned above. Finally, the JNK agonist AN was chosen for reverse research. As shown by the results, the therapeutic effects of MVC disappeared after AN treatment, indicating that MVC exerted anti-inflammatory and antiapoptotic effects through JNK. Our study revealed that MVC could reduce liver injury after SALI by inhibiting liver inflammation and hepatocyte apoptosis induced by CLP and that MVC exerted diminish inflammatory effects by inhibiting the NF-κB and MAPK signaling pathways.

Fabrication of novel nitrogen-doped porous carbon nanospheres for high-performance supercapacitors.

A completely new type of nitrogen-doped polymer nanosphere and the derived nitrogen-doped porous carbon nanospheres were produced by taking 2,4-diamino-6-hydroxypyrimidine as the precursor. When functioning as electrode materials, they demonstrated extraordinary electrochemical performance, offering a powerful candidate for supercapacitors.

High-resolution magnetic resonance imaging features of time-of-flight magnetic resonance angiography signal loss and its relevance to ischemic stroke.

Background: Focal signal loss of intracranial artery stenosis is commonly observed on three-dimensional time-of-flight magnetic resonance angiography (3D-TOF-MRA). We aimed to investigate the underlying pathophysiology of vessel signal loss observed on 3D-TOF-MRA and its relevance to recent ischemic stroke. Methods: High-resolution magnetic resonance imaging (HR-MRI) was performed in 401 patients with unilateral or bilateral moderate-to-severe stenosis (50-99%) of the middle cerebral artery (MCA) on TOF-MRA. The patients were classified according to the presence or absence of focal signal loss in the M1 segment of the MCA. The wall features between the vessels with and without signal loss were compared, and their relationship with recent ischemic stroke was analyzed. Results: A total of 414 stenotic lesions caused by atherosclerotic plaque were detected, including 231 with signal loss on TOF-MRA and 183 without. The signal loss group, compared to the group without signal loss, showed a higher degree of stenosis (P<0.001), grade 2 enhanced plaques (82.3% vs. 28.4%; P<0.001), and concentric pattern (63.2% vs. 34.4%; P<0.001). Multivariate analysis suggested grade 2 enhanced plaques and concentric pattern were independently associated with signal loss. Patients in the signal loss group were more likely to have had a recent ischemic stroke (62.4% vs. 40.4%; P<0.001). Conclusions: In addition to the degree of stenosis, the vulnerability and morphology of plaques on HR-MRI may influence signals on 3D-TOF-MRA. The presence of signal loss on 3D-TOF-MRA is associated with recent ischemic stroke.

An Extremely Rare Case of Collision Tumor: A Craniopharyngioma Coexists Pilocytic Astrocytoma.

A 21-year-old man presented with a 2-day history of cephalalgia and a 1-day history of nausea and vomiting. Neuroradiologic imaging revealed a lesion in the third ventricle accompanied by hydrocephalus. After undergoing a ventriculoperitoneal shunt procedure, the patient experienced relief from symptoms. One-month post-shunt, we excised the tumor. Histopathological examination identified it as a rare collision tumor, composed of a mixture of craniopharyngioma and pilocytic astrocytoma. This is an exceedingly rare type of tumor, with no similar cases reported in the existing literature.

A dual-template synergistic assembly strategy towards the synthesis of extra-small nitrogen-doped mesoporous carbon nanospheres with large pores.

Functional mesoporous carbon nanomaterials with large pores and small particle sizes have broad accessibility, but remain challenging to achieve. This study proposed a dual-template synergistic assembly strategy to facilely synthesize extra-small nitrogen-doped mesoporous carbon nanospheres with large pores in a low-cost manner. Directed by the synergistic effect of the combination of surfactants, sodium oleate (anionic surfactant) and triblock copolymer-P123 (nonionic surfactant) were selected as templates to construct nanomicelles (nanoemulsions), which were co-assembled with melamine-based oligomers to form composite nanomicelles, thus obtaining nitrogen-doped mesoporous polymer nanospheres (NMePS) and then nitrogen-doped mesoporous carbon nanospheres (NMeCS). Based on Schiff base chemistry, the melamine-based oligomers with self-assembly capability were synthesized as precursors, which is different from the conventional synthetic route of melamine-formaldehyde resin. The key parameters involved in the route were investigated comprehensively and correlated with the characterization results. Furthermore, the 50 nm-scale particle size and the large mesoporous size of 5.5 nm of NMeCS can facilitate effective mass transport, coupled with their high nitrogen content (15.7 wt%), contributing to their excellent performance in lithium-ion batteries.

[Research progress in the mechanism of intestinal environmental disturbance on the occurrence and development of sepsis-associated liver injury].

Sepsis-associated liver injury (SALI) is a common complication of sepsis, which is characterized by systemic immune disorders induced by sepsis leading to liver damage. Currently, there are no effective treatments for SALI, which is related to its complex pathophysiological mechanisms. In recent years, the disorder of intestinal environment after sepsis has been considered as an important factor for SALI, but the specific molecular mechanism of the above process is still unclear. This article will review the pathological role and molecular mechanisms between intestinal environmental disturbance and SALI, aiming to analyze the potential research direction of SALI and identify potential therapeutic targets for its treatment.

A novel homozygous LRRC6 mutation causes male infertility with asthenozoospermia and primary ciliary dyskinesia in humans.

BACKGROUND: Dysfunction of motile cilia, including respiratory cilia and sperm flagella, typically leads to primary ciliary dyskinesia and male infertility or low fertility in humans. Genetic defects of LRRC6 have been associated with primary ciliary dyskinesia and asthenozoospermia due to abnormal ultrastructure of ciliated axonemes. OBJECTIVES: To identify novel mutations of the LRRC6 gene related to multiple morphological abnormalities of the sperm flagella and male infertility and investigate the underlying molecular mechanisms involved. MATERIALS AND METHODS: The LRRC6 mutations were identified by whole exome sequencing and confirmed with Sanger sequencing. Papanicolaou staining, scanning, and transmission electron microscopy were performed to investigate the morphological and ultrastructural characteristics of spermatozoa. Further tandem mass tagging proteomics analyses were performed to explore the effect of mutations and confirmed by immunostaining and western blotting. Intracytoplasmic sperm injection was applied for the assisted reproductive therapy of males harboring biallelic LRRC6 mutations. RESULTS: In this study, we identified a novel homozygous LRRC6 mutation in a consanguineous family, characterized by asthenozoospermia and primary ciliary dyskinesia. Further Semen parameter and morphology analysis demonstrate that the novel LRRC6 mutation leads to a significant reduction in sperm flagella length, a decrease in sperm progressive motility parameters, and abnormalities of sperm ultrastructure. Specifically, the absence of outer dynein arms and inner dynein arms, and incomplete mitochondrial sheath in the flagellar mid-piece were observed by transmission electron microscopy. In addition, tandem mass tagging proteomics analysis revealed that spermatozoa obtained from patients harboring the LRRC6 mutation exhibited a significant decrease in the expression levels of proteins related to the assembly and function of dynein axonemal arms. Functional analysis revealed that this novel LRRC6 mutation disrupted the function of the leucine-rich repeat containing 6 protein, which in turn affects the expression of the dynein arm proteins and leucine-rich repeat containing 6-interacting proteins CCDC40, SPAG1, and ZMYND10. Finally, we reported a successful pregnancy through assisted reproductive technology with intracytoplasmic sperm injection in the female partner of the proband. DISCUSSION AND CONCLUSION: This study highlights the identification of a novel homozygous LRRC6 mutation in a consanguineous family and its impact on sperm progressive motility, morphology, and sperm kinetics parameters, which could facilitate the genetic diagnosis of asthenozoospermia and offer valuable perspectives for future genetic counseling endeavors.

Trade-offs between grain supply and soil conservation in the Grain for Green Program under changing climate: A case study in the Three Gorges Reservoir region.

Understanding the trade-offs between ecological benefits and cost of grain supply caused by ecosystem restoration is essential for decision-making. Nevertheless, due to climate change, the benefits of ecosystem restoration and cost of grain supply change across various spatial locations, thereby complicating the trade-offs. Taking one of China's largest scale ecosystem restorations, the Grain for Green Program (GGP), as an example, this study used the Three Gorges Reservoir (TGR) region as the case study area and combined the crop environment resource synthesis (CERES)-Crop model, future land-use simulation (FLUS), and the revised universal soil loss equation (RUSLE) to simulate future grain supply and soil erosion during 2021-2050 under three climate change and socioeconomic development scenarios (SSP1-2.6, SSP2-4.5, SSP5-8.5) in the TGR region. The results showed that: (1) Until 2050, the implementation of GGP would bring a large soil conservation benefit by reducing soil erosion of 2.47-5.68 million tons, at the cost of 130,277-660,279 tons decrease in grain production in the TGR region. (2) Under SSP5-8.5 climate change scenario with the highest rainfall in the future, the GGP would maintain the greatest soil conservation benefits, resulting in a total amount of soil erosion decrease by 2.55 to 5.68 million tons. (3) Trade-offs between benefit of reducing soil erosion and cost of grain supply vary considerably across income. Specifically, GGP benefits are greater under low-income and higher-emission scenarios, with significant gains in soil erosion control and less impact on grain supply. In contrast, in high-income and low-emission scenarios, the GGP results in less soil erosion control and greater impact on grain supply.

Maternal smoking, consumption of alcohol, and caffeinated beverages during pregnancy and the risk of childhood brain tumors: a meta-analysis of observational studies.

BACKGROUND: We conducted this meta-analysis to investigate the potential association between maternal smoking, alcohol and caffeinated beverages consumption during pregnancy and the risk of childhood brain tumors (CBTs). METHODS: A thorough search was carried out on PubMed, Embase, Web of Science, Cochrane Library, and China National Knowledge Internet to identify pertinent articles. Fixed or random effects model was applied to meta-analyze the data. RESULTS: The results suggested a borderline statistically significant increased risk of CBTs associated with maternal smoking during pregnancy (OR 1.04, 95% CI 0.99-1.09). We found that passive smoking (OR 1.12, 95% CI 1.03-1.20), rather than active smoking (OR 1.00, 95% CI 0.93-1.07), led to an increased risk of CBTs. The results suggested a higher risk in 0-1 year old children (OR 1.21, 95% CI 0.94-1.56), followed by 0-4 years old children (OR 1.12, 95% CI 0.97-1.28) and 5-9 years old children (OR 1.11, 95% CI 0.95-1.29). This meta-analysis found no significant association between maternal alcohol consumption during pregnancy and CBTs risk (OR 1.00, 95% CI 0.80-1.24). An increased risk of CBTs was found to be associated with maternal consumption of caffeinated beverages (OR 1.16, 95% CI 1.07-1.26) during pregnancy, especially coffee (OR 1.18, 95% CI 1.00-1.38). CONCLUSIONS: Maternal passive smoking, consumption of caffeinated beverages during pregnancy should be considered as risk factors for CBTs, especially glioma. More prospective cohort studies are warranted to provide a higher level of evidence.

Multiple sclerosis and COVID-19: a northern China survey.

BACKGROUND: There is insufficient data on severe acute respiratory syndrome coronavirus type-2 (SARS-CoV-2) infection in Chinese patients with multiple sclerosis (pwMS). This study aims to explore the manifestation of pwMS during the Coronavirus disease 2019 (COVID-19) pandemic and the effect of SARS-CoV-2 infection on the prognosis of MS in northern China. METHODS: In this cross-sectional study, an online self-administered questionnaire and telephone interviews were conducted among pwMS of northern China. Clinical correlation of SARS-CoV-2 infection since the onset of the COVID-19 pandemic in northern China was analyzed. RESULTS: 164 patients with an average age of 38.9 ± 12.2 years were included, of which 57.3% had a disease course ≤ 5 years. 33.5% of the patients were COVID-19 vaccinated. 87.2% received disease-modifying therapy (DMT), and the average immunotherapy duration was 1.9 ± 1.6 years. 83.5% were SARS-CoV-2 infected, 14.6% reported worsening of their original condition after infection, and 5.1% had a relapse of MS. Shorter disease course was independently related to infection risk (P = 0.046), whereas increasing age was related to aggravated behavioral symptoms (P = 0.008). However, gender, vaccination, and DMT were not associated with susceptibility or poor prognosis. CONCLUSION: A shorter disease course is independently associated with an increased risk of SARS-CoV-2 infection, and age is associated with worsening disability. It seems to be safe and necessary to use DMT during the pandemic, however, the use of B cell-depletion agents should be approached with caution.

Oxidative Addition of E-H (E=C, N) Bonds to Transient Uranium(II) Centers.

Two-electron oxidative addition is one of the most important elementary reactions for d-block transition metals but it is uncommon for f-block elements. Here, we report the first examples of intermolecular oxidative addition of E-H (E=C, N) bonds to uranium(II) centers. The transient U(II) species was formed in-situ by reducing a heterometallic cluster featuring U(IV)-Pd(0) bonds with potassium-graphite (KC8). Oxidative addition of C-H or N-H bonds to the U(II) centers was observed when this transient U(II) species was treated with benzene, carbazole or 1-adamantylamine, respectively. The U(II) centers could also react with tetracene, biphenylene or N2O, leading to the formation of arene reduced U(IV) products and uranyl(VI) species via two- or four-electron processes. This study demonstrates that the intermolecular two-electron oxidative addition reactions are viable for actinide elements.

Temporal variation of microbial nutrient limitation in citrus plantations: Insights from soil enzyme stoichiometry.

Soil enzyme carbon (C): nitrogen (N): phosphorous (P) stoichiometry and their vector model has been widely used to elucidate the balance between microbial nutrient requirements and soil nutrient availability. However, limited knowledge is available on the dynamics of soil enzyme stoichiometry and microbial nutrient limitation following afforestation, especially in the economic forest. In this study, the effects of citrus plantation on C: N: P stoichiometry were assessed through a comparative study between cropland and citrus plantations with varying durations of afforestation (i.e., 3, 15, 25, and 35 years). It was found that the C, N, and P contents in the soil (SOC, STN, and STP), microbial biomass (MBC, MBN, and MBP), as well as the activities of C-, N-, and P-acquiring enzymes (BG, NAG, and AP), were 1.02-2.51 times higher than those in cropland. Additionally, C, N, and P contents in soil and microbial biomass increased consistently with increasing afforestation time. While the activities of C-, N-, and P-acquiring enzymes increased from 3 years to 25 years and then significantly decreased. In addition to NAG: AP, the stoichiometry of C, N, and P in soil (SOC: STN, SOC: STP, and STN: STP) and microbial biomass (MBC: MBN, MBC: MBP, and MBN: MBP), along with BG: NAG, exhibited a decline of 7.69-27.38% compared to cropland. Moreover, the majority of the C: N: P stoichiometry in soil, microbial biomass, and enzymes consistently decreased with increasing afforestation time, except for SOC: STN and NAG: AP, which exhibited an opposite trend. Furthermore, a significant decrease in microbial carbon limitation and an increase in microbial nitrogen limitation were observed with increasing afforestation time. Collectively, the dynamic of microbial nutrient limitation was primarily influenced by the interaction between soil nutrients and edaphic factors. The findings suggest that with the increasing duration of citrus plantation, it is crucial to focus on nitrogen (N) fertilization while maintaining a delicate balance between fertilization strategies and soil acidity levels.

Multiplicative joint coding in preparatory activity for reaching sequence in macaque motor cortex.

Although the motor cortex has been found to be modulated by sensory or cognitive sequences, the linkage between multiple movement elements and sequence-related responses is not yet understood. Here, we recorded neuronal activity from the motor cortex with implanted micro-electrode arrays and single electrodes while monkeys performed a double-reach task that was instructed by simultaneously presented memorized cues. We found that there existed a substantial multiplicative component jointly tuned to impending and subsequent reaches during preparation, then the coding mechanism transferred to an additive manner during execution. This multiplicative joint coding, which also spontaneously emerged in recurrent neural networks trained for double reach, enriches neural patterns for sequential movement, and might explain the linear readout of elemental movements.

Development and validation of a nomogram prediction model for ADHD in children based on individual, family, and social factors.

OBJECTIVES: A reliable, user-friendly, and multidimensional prediction tool can help to identify children at high risk for ADHD and facilitate early recognition and family management of ADHD. We aimed to develop and validate a risk nomogram for ADHD in children aged 3-17 years in the United States based on clinical manifestations and complex environments. METHODS: A total of 141,356 cases were collected for the prediction model. Another 54,444 cases from a new data set were utilized for performing independent external validation. The LASSO regression was used to control possible variables. A final risk nomogram for ADHD was established based on logistic regression, and the discrimination and calibration of the established nomogram were evaluated by bootstrapping with 1000 resamples. RESULTS: A final risk nomogram for ADHD was established based on 13 independent predictors, including behavioral problems, learning disabilities, age, intellectual disabilities, anxiety symptoms, gender, premature birth, maternal age at childbirth, parent-child interaction patterns, etc. The C-index of this model was 0.887 in the training set, and 0.862 in the validation set. Internal and external validation proved that the model was reliable. CONCLUSIONS: A nomogram, a statistical prediction tool that assesses individualized ADHD risk for children is helpful for the early identification of children at high risk for ADHD and the construction of a conceptual model of society-family-school collaborative diagnosis, treatment, and management of ADHD.

A Five-gene Signature based on MicroRNA for Predicting Prognosis and Immunotherapy in Stomach Adenocarcinoma.

AIMS: We aimed to classify molecular subtypes and establish a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in Stomach adenocarcinoma (STAD). BACKGROUND: STAD is a common diagnosed gastrointestinal malignancy and its heterogeneity is a big challenge that influences prognosis and precision therapies. Present study was designed to classify molecular subtypes and construct a prognostic gene signature based on miRNAs for the prognostic prediction and therapeutic response in STAD. OBJECTIVE: The objective of this study is to investigate the molecular subtypes and prognostic model for STAD. METHODS: A STAD specific miRNA-messenger RNA (mRNA) competing endogenous RNA (ceRNA) network was generated using the RNA-Seq and miRNA expression profiles from The Cancer Genome Atlas (TCGA) database, in which miRNA-related mRNAs were screened. Molecular subtypes were then determined using miRNA-related genes. Through univariate Cox analysis and multivariate regression analysis, a prognostic model was established in GSE84437 Train dataset and validated in GSE84437 Test, TCGA, GSE84437 and GSE66229 datasets. Immunotherapy datasets were employed for assessing the performance of the risk model. Finally, quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was applied to validate the expression of hub genes used for the risk score signature. RESULTS: We constructed a ceRNA network containing 84 miRNAs and 907 mRNAs and determined two molecular subtypes based on 26 genes from the intersection of TCGASTAD and GSE84437 datasets. Subtype S2 had poor prognosis, lower tumor mutational burden, higher immune score and lower response to immunotherapy. Subtype S1 was more sensitive to Sorafenib, Pyrimethamine, Salubrinal, Gemcitabine, Vinorelbine and AKT inhibitor VIII. Next, a five-gene signature was generated and its robustness was validated in Test and external datasets. This risk model also had a good prediction performance in immunotherapy datasets. CONCLUSION: This study promotes the underlying mechanisms of miRNA-based genes in STAD and offers directions for classification. A five-gene signature accurately predicts the prognosis and helps therapeutic options.

Temperature induced single-crystal to single-crystal transformation of uranium azide complexes.

The monomeric and dimeric uranium azide complexes {[(CH3)2NCH2CH2NPiPr2]2U(N3)2} (2) and {[(CH3)2NCH2CH2NPiPr2]2U(N3)2}2 (3) were synthesized by treating complex 1 with NaN3 at 60 and -20 °C, respectively. A temperature-induced single-crystal to single-crystal transformation of 3 to 2 was observed. The reduction of either 2 or 3 with KC8 yields a uranium nitride complex {[(CH3)2NCH2CH2NPiPr2]4U2(µ-N)2} (4).

Estimation of spatial distribution of soil moisture on steep hillslopes by state-space approach (SSA).

Soil moisture is a critical variable that quantifies precipitation, floods, droughts, irrigation, and other factors with regard to decision-making and risk evaluation. An accurate prediction of soil moisture dynamics is important for soil and environmental management. However, the complex topographic condition and land use in hilly and mountainous areas make it a challenge to monitor and predict soil moisture dynamics in these areas. In this study, the determinants of soil moisture variability were determined by structural equation modeling, and then an attempt was made to estimate the spatial distribution of soil moisture content on steep hillslope using the state-space method. Herein, soil moisture at different depths (0-10, 10-20, and 20-30 cm) was monitored by portable time-domain reflectometer (TDR) along this hillslope (100 m × 180 m). It showed that the spatial variability of soil moisture decreased with increasing soil wetness, primarily in the topsoil (0-10 cm). Soil moisture was correlated with elevation (r = 0.28, 0.50, and 0.28), capillary porosity (r = 0.06, 0.37, and 0.28), soil texture (r for Clay: 0.20, 0.24, and 0.16; r for Sand: -0.25, -0.18, and -0.28), organic carbon (r = -0.31, -0.08, and 0.10) and land use (r = -0.01, 0.28, and 0.24) under different conditions (dry, moderate, and wet). Among these determinants, elevation made direct contributions to soil moisture variation, especially under moderate conditions, while land use made its impacts by altering soil texture. It is encouraging that the state-space approach yielded precise and cost-effective predictions of soil moisture dynamics along this steep hillslope since it gives the minimum root-mean-square error (RMSE) and Akaike information criterion (AIC). Moreover, soil organic carbon (AIC = -4.497, RMSE = 0.104, R2 = 0.899), rock fragment contents (AIC = -4.366, RMSE = 0.111, R2 = 0.878), and elevation (AIC = -3.693, RMSE = 0.156, R2 = 0.629) effectively anticipated the spatial distribution of soil moisture under dry, moderate, and wet conditions, respectively. This study confirms the efficacy of the state-space approach as a valuable tool for soil moisture prediction in areas characterized by complex and spatially heterogeneous conditions.

Targeting TNFAIP2 induces immunogenic cell death and sensitizes glioblastoma multiforme to anti-PD-1 therapy.

BACKGROUND: The efficacy of current immunotherapeutic strategies for patients with glioblastoma multiforme (GBM) remains unsatisfactory. The purpose of this study was to investigate the correlation between tumor necrosis factor alpha-induced protein 2 (TNFAIP2) and immunogenic cell death (ICD) in GBM, and to examine the effect of TNFAIP2 knockdown and anti-PD-1 combination treatment in a mouse glioma model. METHODS: The CGGA and TCGA databases were used to explore the possible function of TNFAIP2 in GBM. Multiplex immunohistochemistry (mIHC) staining was performed to detect the immune infiltration of tissues. Western blot, quantitative real-time polymerase chain reaction (qRT-PCR), flow cytometry, and enzyme linked immunosorbent assay (ELISA) were utilized to detect the release of damage-associated molecular patterns (DAMPs) and the activation of the immune response. A mouse glioma model was applied to examine the induction of immune response. RESULTS: In vitro and in vivo studies demonstrated that TNFAIP2 knockdown increased the surface exposure of calreticulin (CALR), heat shock protein 70 kDa (HSP70), and heat shock protein 90 kDa (HSP90) in GBM cell lines, thereby inducing immunogenic cell death (ICD). Importantly, the study found that TNFAIP2 knockdown in combination with anti-PD-1 therapy significantly improved the overall survival of glioma in a mouse model. CONCLUSIONS: TNFAIP2 knockdown induces ICD by downregulating TNFAIP2 in GBM. In addition, TNFAIP2 knockdown sensitized glioma to anti-PD-1 therapy. Hence, targeting TNFAIP2 alone or in combination with anti-PD-1 therapy may be a potential strategy for GBM treatment through ICD.

Dysregulated ceramides metabolism via PTPN11 exposes a metabolic vulnerability to breast cancer metastasis.

Breast cancer is a prevalent malignant tumor, posing a significant threat to women's health globally due to its increasing incidence and tendency to affect younger patients. Protein tyrosine phosphatases (PTPs) are a class of enzymes that have emerged as potential targets for various tumors, including breast cancer, because they can modulate oncogenic tyrosine kinases, which are both tumor-suppressive and oncogenic. The regulation of tyrosine phosphorylation levels is crucial for cell proliferation and differentiation. Although the clinical biomarker potential of PTPs is not fully explored, there is evidence to suggest that they may serve as clinical biomarkers and therapeutic targets for breast cancer. We found that increased expression levels of PTPN11 and PTPN3 were associated with a higher risk of death in patients with breast cancer, while PTPN11 and PTPN18 are significantly associated with overall survival in patients with estrogen receptor-positive (ER+) breast cancer. Meanwhile, PTPN11 expression was found to be negatively associated with survival in patients with ER+ breast cancer. Furthermore, PTPN11 exposes a metabolic vulnerability to breast cancer metastasis via dysregulated ceramide metabolism. Therefore, we speculate that PTPN11 has the potential to serve as a therapeutic target for breast cancer by regulating lipid metabolism reprogramming.