Heavy metal sorption on struvite recovered from livestock wastewaters and release properties of granular forms.

Phosphorus recovery from wastewater is receiving more attention due to its non-renewable property. As copper (Cu) and zinc (Zn) usually occur in livestock wastewater, this study focused on metal sorption in struvite from swine wastewater and the release properties of granular struvite in solution with varying pH conditions (2, 4, 7). The results demonstrated pH values presented a slightly decreasing trend with increasing Cu/Zn ratio, and Zn exhibited higher sorption performance on struvite crystals than that of Cu. Under the high content of metals in the wastewater, Cu/Zn ratios in the wastewater contributed to varying metal binding forms and mechanisms, resulting in the difference in the leaching properties of nutrients and metal. For the granular struvite manufactured with the adhesion of alginate, the P release percentage achieved 30.3-40.5% after 96 h in the wastewater of pH 2, whereas they were only 5.63-8.92% and 1.05-1.50% in the wastewater of pH 4 and 7, respectively. Acid wastewater contributed to the release of two metals, and the release amount of Zn was higher than that of Cu, which is associated with their sorption capacity in crystals. During the latter soil leaching test of adding granular struvite, the NH4+-N and PO43--P concentration in the effluent ranged from 0.34 to 1.26 and 0.62 to 2.56 mg/L after 96 h, respectively. However, the Cu and Zn could not be measured due to lower than the detection limit under varying treatments. Struvite might be accompanied by quicker metal leaching and slower nutrient leaching when surface sorption dominates in wastewater with lower metal concentrations.

Efficacy and relative safety of caplacizumab in immune-mediated thrombotic thrombocytopenic purpura: a systematic review and meta-analysis.

Immune-mediated thrombotic thrombocytopenia purpura (iTTP) is a rare microvascular disease characterized by severe disseminated microvascular thrombose-bleeding syndrome. Caplacizumab has been approved for the treatment of iTTP in combination with Plasma Exchange (PE) and immunosuppressive therapy, but its role in iTTP therapy remains uncertain. Therefore, we conducted a meta-analysis to investigate the safety and efficacy of caplacizumab for the treatment of patients with iTTP. We searched electronic databases (PubMed, Embase, Cochrane Library, and Scopus) and reference lists of relevant articles to find articles published from 2015 to 2022. The time to normalization of the platelet count of the group caplacizumab is shorter than the group placebo (SMD = -0.72; 95% CI -0.88 to -0.56; P  < 0.05). Caplacizumab reduced the incidence of mortality (OR = 0.41; 95% CI 0.18-0.92; P  < 0.05), exacerbations (OR = 0.10; 95% CI 0.05-0.18; P  < 0.05), and recurrence (OR = 0.17; 95% CI 0.06-0.50; P  < 0.05). However, the bleeding events in the caplacizumab group were higher than those in the placebo group, especially severe bleeding events. There was no difference in ADAMTS13 activity and thromboembolic events between the two groups. Our analysis indicated that caplacizumab is effective and well tolerated for the treatment of iTTP. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42022362370.

The Relationship Between the hOGG1 rs1052133 Polymorphism and the Occurrence of Nasopharyngeal Carcinoma: A Systematic Review and Meta-Analysis.

Objectives: Exploring the relationship between the hOGG1 rs1052133 polymorphism and the occurrence of nasopharyngeal carcinoma (NPC). Methods: PubMed, Web of Science, Scopus, CNKI, Wanfangdata, and VIP were used to search for studies and the NOS evaluation scale was used to evaluate the quality. All studies were grouped according to different genotypes. The Cochrane's Q test and I2 test were used for heterogeneity evaluations. If heterogeneity was small, the fixed effects model was used, and conversely, the random effects model was used. Publication bias was also detected. P < .05 in all results indicated statistically significant. Results: We ultimately included 6 studies with 2021 NPC patients in the study group and 2375 healthy populations in the control group. After meta-analysis, it was found that the total OR value of the "Ser/Cys (CG) vs Ser/Ser (CC)" group was 1.00 (95% CI: 0.85-1.18) and the "Cys/Cys (GG) vs Ser/Ser (CC)" group was 1.06 (95% CI: 0.87-1.28). These results were not statistically significant (P > .05). Furthermore, the integrated total OR values of each group were not statistically significant with or without the smoking history, even in other genotype models (Allele, Dominant, Recessive, and Additive) (P > .05). Conclusion: There is no clear correlation between the hOGG1 rs1052133 polymorphism and the occurrence of NPC, even with or without the smoking history.

The efficacy and safety of adding PD-1 blockade to induction chemotherapy and concurrent chemoradiotherapy (IC-CCRT) for locoregionally advanced nasopharyngeal carcinoma: an observational, propensity score-matched analysis.

BACKGROUND: Despite the success of PD-1 blockade in recurrent/metastatic nasopharyngeal carcinoma (NPC), its effect for locoregionally advanced NPC (LANPC) remains unclear. This study aimed to evaluate the benefit of adding PD-1 blockade to the current standard treatment (gemcitabine and cisplatin IC  plus cisplatin CCRT ) for LANPC patients. METHODS: From January 2020 to November 2022, 347 patients with non-metastatic high-risk LANPC (stage III-IVA, excluding T3-4N0) were included. Of the 347 patients, 268 patients were treated with standard treatment (IC-CCRT), and 79 received PD-1 blockade plus IC-CCRT (PD-1 group). For the PD-1 group, PD-1 blockade was given intravenously once every 3 weeks for up to 9 cycles (3 induction and 6 adjuvant). The primary endpoint was disease-free survival (DFS) (i.e. freedom from local/regional/distant failure or death). The propensity score matching (PSM) with the ratio of 1:2 was performed to control confounding factors. RESULTS: After PSM analysis, 150 patients receiving standard treatment and 75 patients receiving additional PD-1 blockade remained in the current analysis. After three cycles of IC, the PD-1 group had significantly higher rates of complete response (defined as disappearance of all target lesions; 24% vs. 9%; P = 0.006) and complete biological response (defined as undetectable cell-free Epstein-Barr virus DNA, cfEBV DNA; 79% vs. 65%; P = 0.046) than that in the standard group. And the incidence of grade 3-4 toxicity during IC was 47% in the PD-1 group and 41% in the standard group, with no significant difference (P = 0.396). During follow-up period, additional PD-1 blockade to standard treatment improved 3-year DFS from 84 to 95%, with marginal statistical significance (HR, 0.28; 95%CI, 0.06-1.19; P = 0.064). CONCLUSION: Additiaonl PD-1 blockade to gemcitabine and cisplatin IC and adjuvant treatment results in significant improvement in tumor regression, cfEBV DNA clearance, superior DFS, and comparable toxicity profiles in high-risk LANPC patients.

Oxygen Radical Coupling on Short-Range Ordered Ru Atom Arrays Enables Exceptional Activity and Stability for Acidic Water Oxidation.

The discovery of efficient and stable electrocatalysts for oxygen evolution reaction (OER) in acid is vital for the commercialization of the proton-exchange membrane water electrolyzer. In this work, we demonstrate that short-range Ru atom arrays with near-ideal Ru-Ru interatomic distances and a unique Ru-O hybridization state can trigger direct O*-O* radical coupling to form an intermediate O*-O*-Ru configuration during acidic OER without generating OOH* species. Further, the Ru atom arrays suppress the participation of lattice oxygen in the OER and the dissolution of active Ru. Benefiting from these advantages, the as-designed Ru array-Co3O4 electrocatalyst breaks the activity/stability trade-off that plagues RuO2-based electrocatalysts, delivering an excellent OER overpotential of only 160 mV at 10 mA cm-2 in 0.5 M H2SO4 and outstanding durability during 1500 h operation, representing one of the best acid-stable OER electrocatalysts reported to date. 18O-labeled operando spectroscopic measurements together with theoretical investigations revealed that the short-range Ru atom arrays switched on an oxide path mechanism (OPM) during the OER. Our work not only guides the design of improved acidic OER catalysts but also encourages the pursuit of short-range metal atom array-based electrocatalysts for other electrocatalytic reactions.

RUNX1::ETO and CBFß::MYH11 converge on aberrant activation of BCAT1 to confer a therapeutic vulnerability in core-binding factor-acute myeloid leukaemia.

Effectively targeting transcription factors in therapeutic interventions remains challenging, especially in core-binding factor-acute myeloid leukaemia (CBF-AML) characterized by RUNX1::ETO and CBFß::MYH11 fusions. However, recent studies have drawn attention towards aberrant amino acid metabolisms as actionable therapeutic targets. Here, by integrating the expression profile and genetic makeup in AML cohort, we found higher BCAT1 expression in CBF-AML patients compared with other subtypes. Metabolic profiling revealed that high BCAT1 expression led to reprogrammed branch amino acid metabolism in CBF-AML and was associated with sphingolipid pathway relating to the fitness of leukaemia cells, supported by transcriptomic profiling. Mechanistically, we demonstrated in cell lines and primary patient samples that BCAT1 was directly activated by RUNX1::ETO and CBFß::MYH11 fusion proteins similarly in a RUNX1-dependent manner through rewiring chromatin conformation at the BCAT1 gene locus. Furthermore, BCAT1 inhibition resulted in blunted cell cycle, enhanced apoptosis and myeloid differentiation of CBF-AML cells in vitro, and alleviated leukaemia burden and prolonged survival in vivo. Importantly, pharmacological inhibition of BCAT1 using the specific inhibitor Gabapentin demonstrated therapeutic effects, as evidenced by delayed leukaemia progression and improved survival in vivo. In conclusion, our study uncovers BCAT1 as a genetic vulnerability and a promising targeted therapeutic opportunity for CBF-AML.

Spectroscopic analysis of the sum-frequency response of the carbon-hydrogen stretching modes in collagen type I.

We studied the origin of the vibrational signatures in the sum-frequency generation (SFG) spectrum of fibrillar collagen type I in the carbon-hydrogen stretching regime. For this purpose, we developed an all-reflective, laser-scanning SFG microscope with minimum chromatic aberrations and excellent retention of the polarization state of the incident beams. We performed detailed SFG measurements of aligned collagen fibers obtained from rat tail tendon, enabling the characterization of the magnitude and polarization-orientation dependence of individual tensor elements Xijk2 of collagen's nonlinear susceptibility. Using the three-dimensional atomic positions derived from published crystallographic data of collagen type I, we simulated its Xijk2 elements for the methylene stretching vibration and compared the predicted response with the experimental results. Our analysis revealed that the carbon-hydrogen stretching range of the SFG spectrum is dominated by symmetric stretching modes of methylene bridge groups on the pyrrolidine rings of the proline and hydroxyproline residues, giving rise to a dominant peak near 2942 cm-1 and a shoulder at 2917 cm-1. Weak asymmetric stretches of the methylene bridge group of glycine are observed in the region near 2870 cm-1, whereas asymmetric CH2-stretching modes on the pyrrolidine rings are found in the 2980 to 3030 cm-1 range. These findings help predict the protein's nonlinear optical properties from its crystal structure, thus establishing a connection between the protein structure and SFG spectroscopic measurements.

Comparative Bioequivalence and Food Effect of Two Formulations of 30-mg Nifedipine Controlled-Release Tablets in Healthy Chinese Adults.

Nifedipine is a potent antihypertensive medication classified as a dihydropyridine calcium channel blocker. The objective of this trial was to assess the bioequivalence of a 30-mg nifedipine controlled-release tablet and a reference drug in a cohort of healthy Chinese individuals. Two independent open-label, randomized, single-dose, crossover studies were conducted, 1 under fasting conditions (N = 44, with 1 participant dropping out midway) and the other under fed conditions (N = 44, with 4 participants dropping out midway). Plasma concentrations of nifedipine were determined using liquid chromatography-mass spectrometry, and pharmacokinetic (PK) parameters were calculated using noncompartmental analysis with Phoenix WinNonlin 8.0 software. In both fasting and fed studies, reasonable bioequivalence was observed for the PK parameters of both the test product and the reference drug. A good safety profile was demonstrated for both the test product and reference drug, with no serious adverse events reported, and both were similarly well tolerated. An important observation with food coadministration was that systemic exposure to nifedipine (based on area under the curve, AUC0-∞) was reduced by approximately 12%. The bioequivalence of the test product and reference drug under fasting/fed conditions in healthy subjects in China was demonstrated by the study results.

Multiparametric evaluation of mediastinal lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers.

OBJECTIVES: This study aimed to determine the predictive factors of lymph node metastases in clinical T0-T1c stage non-small-cell lung cancers, so as to help making surgical strategy. METHODS: From January 2016 to December 2017, patients with clinical T0-T1c stage non-small-cell lung cancers were retrospectively reviewed. We elucidated the lymph node metastatic incidence and distribution according to the primary tumour radiographic findings and maximal standard uptake values, and extracted the associated clinicopathological factors. Univariable and multivariable logistic regressions were used to identify independent predictive parameters for lymph node metastases. The performance of predictive model was evaluated using receiver operating characteristic analysis. RESULTS: A total of 517 patients were included. Seventy-two patients had lymph node metastases. Among patients with pure ground-glass nodule and solid component size ≤10 mm, none had any lymph node metastasis. Multivariable logistic regression analysis demonstrated that age, carcinoembryonic antigen level, solid component size, consolidation-tumour ratio and tumour maximal standard uptake values were independent predictors of lymph nodal metastases. Receiver operating characteristic analyses indicated that the area under the curve of predictive model in evaluating lymph node metastases was 0.838 (95% CI 0.791-0.886). CONCLUSIONS: Younger age, elevated carcinoembryonic antigen level, larger solid component size, higher consolidation-tumour ratio and tumour maximal standard uptake values were associated with lymph node involvement. Employing such a predictive model in the future may affect the surgical option of lymph node excision for patients in cT1 stage non-small-cell lung cancer.

Mutant U2AF1-Induced Mis-Splicing of mRNA Translation Genes Confers Resistance to Chemotherapy in Acute Myeloid Leukemia.

Patients with primary refractory acute myeloid leukemia (AML) have a dismal long-term prognosis. Elucidating the resistance mechanisms to induction chemotherapy could help identify strategies to improve AML patient outcomes. Herein, we retrospectively analyzed the multiomics data of more than 1,500 AML cases and found that patients with spliceosome mutations had a higher risk of developing refractory disease. RNA splicing analysis revealed that the mis-spliced genes in refractory patients converged on translation-associated pathways, promoted mainly by U2AF1 mutations. Integrative analyses of binding and splicing in AML cell lines substantiated that the splicing perturbations of mRNA translation genes originated from both the loss and gain of mutant U2AF1 binding. In particular, the U2AF1S34F and U2AF1Q157R mutants orchestrated the inclusion of exon 11 (encoding a premature termination codon) in the eukaryotic translation initiation factor 4A2 (EIF4A2). This aberrant inclusion led to reduced eIF4A2 protein expression via nonsense-mediated mRNA decay. Consequently, U2AF1 mutations caused a net decrease in global mRNA translation that induced the integrated stress response (ISR) in AML cells, which was confirmed by single-cell RNA sequencing. The induction of ISR enhanced the ability of AML cells to respond and adapt to stress, contributing to chemoresistance. A pharmacologic inhibitor of ISR, ISRIB, sensitized U2AF1 mutant cells to chemotherapy. These findings highlight a resistance mechanism by which U2AF1 mutations drive chemoresistance and provide a therapeutic approach for AML through targeting the ISR pathway. SIGNIFICANCE: U2AF1 mutations induce the integrated stress response by disrupting splicing of mRNA translation genes that improves AML cell fitness to enable resistance to chemotherapy, which can be targeted to improve AML treatment.

A Case of High-Altitude Renal Syndrome.

Wang, Si-Yang, Jun Liang, and Jing-Hong Zhao. A Case of High-Altitude Renal Syndrome. High Alt Med Biol. 00:000-000, 2024.-Epidemiological studies have confirmed that high-altitude exposure increases the risk of proteinuria. The concept of high-altitude renal syndrome (HARS) was proposed in 2011. HARS is a group of clinical syndromes consisting of high-altitude polycythemia, hyperuricemia, systemic hypertension, and microalbuminuria. At present, no standardized and unified treatment methods of HARS have been proposed. We report a case of HARS without other organ involvement in a young man exposed to high altitude. Decreasing the red blood cell count and hemodynamic changes as soon as possible may be of great importance for reducing proteinuria. In addition, angiotensin receptor blockers are effective in the treatment of HARS.

Phantom study and clinical application of total-body 18F-FDG PET/CT imaging: How to use small voxel imaging better?

BACKGROUND: Conventional PET/CT imaging reconstruction is typically performed using voxel size of 3.0-4.0 mm in three axes. It is hypothesized that a smaller voxel sizes could improve the accuracy of small lesion detection. This study aims to explore the advantages and conditions of small voxel imaging on clinical application. METHODS: Both NEMA IQ phantom and 30 patients with an injected dose of 3.7 MBq/kg were scanned using a total-body PET/CT (uEXPLORER). Images were reconstructed using matrices of 192 × 192, 512 × 512, and 1024 × 1024 with scanning duration of 3 min, 5 min, 8 min, and 10 min, respectively. RESULTS: In the phantom study, the contrast recovery coefficient reached the maximum in matrix group of 512 × 512, and background variability increased as voxel size decreased. In the clinical study, SUVmax, SD, and TLR increased, while SNR decreased as the voxel size decreased. When the scanning duration increased, SNR increased, while SUVmax, SD, and TLR decreased. The SUVmean was more reluctant to the changes in imaging matrix and scanning duration. The mean subjective scores for all 512 × 512 groups and 1024 × 1024 groups (scanning duration ≥ 8 min) were over three points. One false-positive lesion was found in groups of 512 × 512 with scanning duration of 3 min, 1024 × 1024 with 3 min and 5 min, respectively. Meanwhile, the false-negative lesions found in group of 192 × 192 with duration of 3 min and 5 min, 512 × 512 with 3 min and 1024 × 1024 with 3 min and 5 min were 5, 4, 1, 4, and 1, respectively. The reconstruction time and storage space occupation were significantly increased as the imaging matrix increased. CONCLUSIONS: PET/CT imaging with smaller voxel can improve SUVmax and TLR of lesions, which is advantageous for the diagnosis of small or hypometabolic lesions if with sufficient counts. With an 18F-FDG injection dose of 3.7 MBq/kg, uEXPLORER PET/CT imaging using matrix of 512 × 512 with 5 min or 1024 × 1024 with 8 min can meet the image requirements for clinical use.

Toripalimab Plus Chemotherapy for Recurrent or Metastatic Nasopharyngeal Carcinoma: The JUPITER-02 Randomized Clinical Trial.

Importance: There are currently no therapies approved by the US Food and Drug Administration for nasopharyngeal carcinoma (NPC). Gemcitabine-cisplatin is the current standard of care for the first-line treatment of recurrent or metastatic NPC (RM-NPC). Objective: To determine whether toripalimab in combination with gemcitabine-cisplatin will significantly improve progression-free survival and overall survival as first-line treatment for RM-NPC, compared with gemcitabine-cisplatin alone. Design, Setting, and Participants: JUPITER-02 is an international, multicenter, randomized, double-blind phase 3 study conducted in NPC-endemic regions, including mainland China, Taiwan, and Singapore. From November 10, 2018, to October 20, 2019, 289 patients with RM-NPC with no prior systemic chemotherapy in the RM setting were enrolled from 35 participating centers. Interventions: Patients were randomized (1:1) to receive toripalimab (240 mg [n = 146]) or placebo (n = 143) in combination with gemcitabine-cisplatin for up to 6 cycles, followed by maintenance with toripalimab or placebo until disease progression, intolerable toxicity, or completion of 2 years of treatment. Main Outcome: Progression-free survival as assessed by a blinded independent central review. Secondary end points included objective response rate, overall survival, progression-free survival assessed by investigator, duration of response, and safety. Results: Among the 289 patients enrolled (median age, 46 [IQR, 38-53 years; 17% female), at the final progression-free survival analysis, toripalimab treatment had a significantly longer progression-free survival than placebo (median, 21.4 vs 8.2 months; HR, 0.52 [95% CI, 0.37-0.73]). With a median survival follow-up of 36.0 months, a significant improvement in overall survival was identified with toripalimab over placebo (hazard ratio [HR], 0.63 [95% CI, 0.45-0.89]; 2-sided P = .008). The median overall survival was not reached in the toripalimab group, while it was 33.7 months in the placebo group. A consistent effect on overall survival, favoring toripalimab, was found in subgroups with high and low PD-L1 (programmed death-ligand 1) expression. The incidence of all adverse events, grade 3 or greater adverse events, and fatal adverse events were similar between the 2 groups. However, adverse events leading to discontinuation of toripalimab or placebo (11.6% vs 4.9%), immune-related adverse events (54.1% vs 21.7%), and grade 3 or greater immune-related adverse events (9.6% vs 1.4%) were more frequent in the toripalimab group. Conclusions and Relevance: The addition of toripalimab to chemotherapy as first-line treatment for RM-NPC provided statistically significant and clinically meaningful progression-free survival and overall survival benefits compared with chemotherapy alone, with a manageable safety profile. These findings support the use of toripalimab plus gemcitabine-cisplatin as the new standard of care for this patient population. Trial Registration: ClinicalTrials.gov Identifier: NCT03581786.

Reconstructing the cytokine view for the multi-view prediction of COVID-19 mortality.

BACKGROUND: Coronavirus disease 2019 (COVID-19) is a rapidly developing and sometimes lethal pulmonary disease. Accurately predicting COVID-19 mortality will facilitate optimal patient treatment and medical resource deployment, but the clinical practice still needs to address it. Both complete blood counts and cytokine levels were observed to be modified by COVID-19 infection. This study aimed to use inexpensive and easily accessible complete blood counts to build an accurate COVID-19 mortality prediction model. The cytokine fluctuations reflect the inflammatory storm induced by COVID-19, but their levels are not as commonly accessible as complete blood counts. Therefore, this study explored the possibility of predicting cytokine levels based on complete blood counts. METHODS: We used complete blood counts to predict cytokine levels. The predictive model includes an autoencoder, principal component analysis, and linear regression models. We used classifiers such as support vector machine and feature selection models such as adaptive boost to predict the mortality of COVID-19 patients. RESULTS: Complete blood counts and original cytokine levels reached the COVID-19 mortality classification area under the curve (AUC) values of 0.9678 and 0.9111, respectively, and the cytokine levels predicted by the feature set alone reached the classification AUC value of 0.9844. The predicted cytokine levels were more significantly associated with COVID-19 mortality than the original values. CONCLUSIONS: Integrating the predicted cytokine levels and complete blood counts improved a COVID-19 mortality prediction model using complete blood counts only. Both the cytokine level prediction models and the COVID-19 mortality prediction models are publicly available at http://www.healthinformaticslab.org/supp/resources.php .

TBC-YOLOv7: a refined YOLOv7-based algorithm for tea bud grading detection.

Introduction: Accurate grading identification of tea buds is a prerequisite for automated tea-picking based on machine vision system. However, current target detection algorithms face challenges in detecting tea bud grades in complex backgrounds. In this paper, an improved YOLOv7 tea bud grading detection algorithm TBC-YOLOv7 is proposed. Methods: The TBC-YOLOv7 algorithm incorporates the transformer architecture design in the natural language processing field, integrating the transformer module based on the contextual information in the feature map into the YOLOv7 algorithm, thereby facilitating self-attention learning and enhancing the connection of global feature information. To fuse feature information at different scales, the TBC-YOLOv7 algorithm employs a bidirectional feature pyramid network. In addition, coordinate attention is embedded into the critical positions of the network to suppress useless background details while paying more attention to the prominent features of tea buds. The SIOU loss function is applied as the bounding box loss function to improve the convergence speed of the network. Result: The results of the experiments indicate that the TBC-YOLOv7 is effective in all grades of samples in the test set. Specifically, the model achieves a precision of 88.2% and 86.9%, with corresponding recall of 81% and 75.9%. The mean average precision of the model reaches 87.5%, 3.4% higher than the original YOLOv7, with average precision values of up to 90% for one bud with one leaf. Furthermore, the F1 score reaches 0.83. The model's performance outperforms the YOLOv7 model in terms of the number of parameters. Finally, the results of the model detection exhibit a high degree of correlation with the actual manual annotation results ( R2 =0.89), with the root mean square error of 1.54. Discussion: The TBC-YOLOv7 model proposed in this paper exhibits superior performance in vision recognition, indicating that the improved YOLOv7 model fused with transformer-style module can achieve higher grading accuracy on densely growing tea buds, thereby enables the grade detection of tea buds in practical scenarios, providing solution and technical support for automated collection of tea buds and the judging of grades.

Single-cell dissection of cellular and molecular features underlying mesenchymal stem cell therapy in ischemic acute kidney injury.

Mesenchymal stem cells (MSCs) exert beneficial therapeutic effects in acute kidney injury (AKI), while the detailed repair mechanism remains unclear. Herein, we probed the underlying mechanisms of MSC therapy in AKI by performing unbiased single-cell RNA sequencing in IRI model with/without MSC treatment. Our analyses uncovered the tubular epithelial cells (TECs) and immune cells transcriptomic diversity and highlighted a repair trajectory involving renal stem/progenitor cell differentiation. Our findings also suggested that profibrotic TECs expressing pro-fibrotic factors such as Zeb2 and Pdgfb promoted the recruitment of inflammatory monocytes and Th17 cells to injured kidney tissue, inducing TGF-ß1 secretion and renal fibrosis. Finally, in addition to activating the repair properties of renal progenitor/stem cells, we uncovered a role for MSC-derived miR-26a-5p in mediating the therapeutic effects of MSCs by inhibiting Zeb2 expression and suppressing pro-fibrotic TECs and its subsequent recruitment of immune cell subpopulations. These findings may help to optimize future AKI treatment strategies.

Efficacy of apatinib combined with temozolomide in the treatment of recurrent high­grade glioma: A meta­analysis.

Recurrent high-grade glioma is a refractory disease, and its prognosis is poor. Although the treatment of apatinib combined with temozolomide provides improved efficacy and is able to prolong survival, this conclusion has been based on small samples. In order to clarify this treatment's efficacy, a meta-analysis was performed in the present study. Different databases were screened and finally, 10 studies were included, comprising 357 patients with recurrent high-grade gliomas. The efficacy and prognosis were analyzed using Stata software. The results indicated that the overall objective response rate (ORR) and disease control rate (DCR) of apatinib combined with temozolomide were 0.36 (95% CI, 0.26-0.46) and 0.86 (95% CI, 0.82-0.89), respectively. Subgroup analysis indicated that the overall ORR was 0.43 (95% CI, 0.29-0.57) and 0.26 (95% CI, 0.14-0.38), and the DCR was 0.89 (95% CI, 0.85-0.93) and 0.76 (95% CI, 0.69-0.84) in the treatment of apatinib with temozolomide dose-dense group and the conventional-dose group (5/28 regimen), respectively. Further prognostic analysis indicated that the median overall survival of patients with high-grade glioma treated with apatinib combined with temozolomide was 8.21 months (95% CI, 7.20-9.22 months) and the median progression-free survival was 5.45 months (95% CI, 4.53-6.37). Analysis of the publication bias of the effect size revealed that there was bias in the DCR, while no bias was found in the remaining effect size (ORR, median overall survival and median progression-free survival). After correction by the trim-and-fill method, bias was indicated to have no significant impact on the results. In conclusion, apatinib combined with temozolomide has the effect that, compared with traditional Bevacizumab treatment, it can improve the efficacy in the treatment of recurrent high-grade glioma and improve prognosis. When combining with dose-dense temozolomide, the effect may be better than that of the conventional 5/28 regimen.

Exposing high-activity (111) facet CoO octahedral loading MXene quantum dots for efficient and stable photocatalytic H2 evolution.

Photocatalytic splitting of water for hydrogen generation is a green and renewable solution for converting solar energy to chemical energy; thus, the development of high-performance and stable photocatalytic materials has emerged as a research hotspot recently. Herein, a heterostructure composite photocatalyst of octahedral CoO uniformly modified with novel nitrogen-doped MXene quantum dots (N-MQDs) is successfully designed using a typical solvothermal approach. The optimum photocatalytic hydrogen evolution efficiency of the prepared N-MQDs@CoO heterojunction composite is 82.54 µmol g-1 h-1 with visible light, which is 16.57 times higher compared to the pure CoO. A series of photoelectrochemical tests were further performed to elucidate the photocatalytic hydrogen evolution mechanism. The remarkable improvement of activity is primarily attributed to the synergistic interaction between the closely spaced interface contacts and energy level matching among high conductivity Ti3C2 MXene quantum dots with CoO octahedra, dramatically hastening the segregation and transfer of photo-generated carriers. This study provides new ideas for the construction of MXene quantum dot-based co-photocatalysts with highly efficient photocatalytic performance and stability toward solar energy conversion applications.

Diagnostic Value of Dynamic 18F-Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography (18F-FDG PET-CT) in Cervical Lymph Node Metastasis of Nasopharyngeal Cancer.

BACKGROUND AND PURPOSE: Dynamic 18F-FDG PET-CT scanning can accurately quantify 18F-FDG uptake and has been successfully applied in diagnosing and evaluating therapeutic effects in various malignant tumors. There is no conclusion as to whether it can accurately distinguish benign and malignant lymph nodes in nasopharyngeal cancer. The main purpose of this study is to reveal the diagnostic value of dynamic PET-CT in cervical lymph node metastasis of nasopharyngeal cancer through analysis. METHOD: We first searched for cervical lymph nodes interested in static PET-CT, measured their SUV-Max values, and found the corresponding lymph nodes in magnetic resonance images before and after treatment. The valid or invalid groups were included according to the changes in lymph node size before and after treatment. If the change in the product of the maximum diameter and maximum vertical transverse diameter of the lymph node before and after treatment was greater than or equal to 50%, they would be included in the valid group. If the change was less than 50%, they would be included in the invalid group. Their Ki values were measured on dynamic PET-CT and compared under different conditions. Then, we conducted a correlation analysis between various factors and Ki values. Finally, diagnostic tests were conducted to compare the sensitivity and specificity of Ki and SUV-Max. RESULT: We included 67 cervical lymph nodes from different regions of 51 nasopharyngeal cancer patients and divided them into valid and invalid groups based on changes before treatment. The valid group included 50 lymph nodes, while the invalid group included 17. There wer significant differences (p < 0.001) between the valid and the invalid groups in SUV-Max, Ki-Mean, and Ki-Max values. When the SUV-Max was ≤4.5, there was no significant difference in the Ki-Mean and Ki-Max between the two groups (p > 0.05). When the SUV-Max was ≤4.5 and pre-treatment lymph nodes were <1.0 cm, the valid group had significantly higher Ki-Mean (0.00910) and Ki-Maximum (0.01004) values than the invalid group (Ki-Mean = 0.00716, Ki-Max = 0.00767) (p < 0.05). When the SUV-Max was ≤4.5, the pre-treatment lymph nodes < 1.0 cm, and the EBV DNA replication normal, Ki-Mean (0.01060) and Ki-Max (0.01149) in the valid group were still significantly higher than the invalid group (Ki-Mean = 0.00670, Ki-Max = 0.00719) (p < 0.05). The correlation analysis between different factors (SUV-Max, T-stage, normal EB virus DNA replication, age, and pre-treatment lymph node < 1.0 cm) and the Ki value showed that SUV-Max and a pre-treatment lymph node < 1.0 cm were related to Ki-Mean and Ki-Max. Diagnostic testing was conducted; the AUC value of the SUV-Max value was 0.8259 (95% confidence interval: 0.7296-0.9222), the AUC value of the Ki-Mean was 0.8759 (95% confidence interval: 0.7950-0.9567), and the AUC value of the Ki-Max was 0.8859 (95% confidence interval: 0.8089-0.9629). After comparison, it was found that there was no significant difference in AUC values between Ki-Mean and SUV-Max (p = 0.220 > 0.05), and there was also no significant difference in AUC values between Ki max and SUV-Max (p = 0.159 > 0.05). By calculating the Youden index, we identified the optimal cut-off value. It was found that the sensitivity of SUV-Max was 100% and the specificity was 66%, the sensitivity of Ki-Mean was 100% and the specificity was 70%, and the sensitivity of Ki-Max was 100% and the specificity was 72%. After Chi-Square analysis, it was found that there was no significant difference in specificity between Ki-Mean and SUV-Max (p = 0.712), and there was also no significant difference in specificity between Ki-Max and SUV-Max (p = 0.755). CONCLUSION: Dynamic PET-CT has shown a significant diagnostic value in diagnosing cervical lymph node metastasis of nasopharyngeal cancer, especially for the small SUV value, and lymph nodes do not meet the metastasis criteria before treatment, and EBV DNA replication is normal. Although the diagnostic accuracy, sensitivity, and specificity of dynamic PET-CT were not significantly different from traditional static PET-CT, the dynamic PET-CT had a more accurate tendency.

The applications and techniques of organoids in head and neck cancer therapy.

Head and neck cancer (HNC) is one of the most common cancers on the planet, with approximately 600,000 new cases diagnosed and 300,000 deaths every year. Research into the biological basis of HNC has advanced slowly over the past decades, which has made it difficult to develop new, more effective treatments. The patient-derived organoids (PDOs) are made from patient tumor cells, resembling the features of their tumors, which are high-fidelity models for studying cancer biology and designing new precision medicine therapies. In recent years, considerable effort has been focused on improving "organoids" technologies and identifying tumor-specific medicine using head and neck samples and a variety of organoids. A review of improved techniques and conclusions reported in publications describing the application of these techniques to HNC organoids is presented here. Additionally, we discuss the potential application of organoids in head and neck cancer research as well as the limitations associated with these models. As a result of the integration of organoid models into future precision medicine research and therapeutic profiling programs, the use of organoids will be extremely significant in the future.