Risk factors and outcome of BK polyomavirus infection in pediatric kidney transplantation.

BACKGROUND: BK polyomavirus (BKV) infection is a critical complication hindering graft survival after kidney transplantation. We aimed to investigate the risk factors and outcome of BKV infection in pediatric kidney transplantation. METHODS: The clinical and follow-up data of pediatric kidney transplant recipients at the Children's Hospital of Fudan University from Jan 2015 to June 2023 were retrospectively analyzed. RESULTS: A total of 217 patients were included in the study with mean follow-up time of 24.3 ± 19.9 months. The mean age at transplantation was 9.7 ± 4.2 years. The patient survival rate and graft survival rate were 98.2% and 96.8%, respectively. Twenty-nine patients (13.4%) developed BKV infection, which was detected at 5.8 ± 3.2 months after transplantation. Among these 29 patients with BKV infection, 8 patients (3.6%) developed BKV nephropathy (BKVN), which was diagnosed at 8.3 ± 2.9 months after transplantation, and 2 patients developed graft failure eventually. Compared with the non-BKV infection group (eGFR 76.7 ± 26.1 mL/min/1.73 m2) and BKV infection without BKVN group (eGFR 85.2 ± 23.8 mL/min/1.73 m2), BKVN group had lowest eGFR during follow-up (33.5 ± 11.0 ml/min/1.73 m2, P < 0.001). Younger age at transplant (OR 0.850, 95%CI 0.762-0.948, P = 0.005), CAKUT disease of primary etiology (OR 2.890, 95%CI 1.200-6.961, P = 0.018), and CMV negative recipient serostatus before transplantation (OR 3.698, 95%CI 1.583-8.640, P = 0.003) were independent risk factors for BKV infection. CONCLUSIONS: Incidence of BKV infection is quite high within 12 months after pediatric kidney transplantation and children with BKVN have poor graft function. Younger age at transplant, CAKUT disease, and CMV negative recipient serostatus before transplantation increase the risk of BKV infection after kidney transplantation.

A kinase fusion protein from Aegilops longissima confers resistance to wheat powdery mildew.

Many disease resistance genes have been introgressed into wheat from its wild relatives. However, reduced recombination within the introgressed segments hinders the cloning of the introgressed genes. Here, we have cloned the powdery mildew resistance gene Pm13, which is introgressed into wheat from Aegilops longissima, using a method that combines physical mapping with radiation-induced chromosomal aberrations and transcriptome sequencing analysis of ethyl methanesulfonate (EMS)-induced loss-of-function mutants. Pm13 encodes a kinase fusion protein, designated MLKL-K, with an N-terminal domain of mixed lineage kinase domain-like protein (MLKL_NTD domain) and a C-terminal serine/threonine kinase domain bridged by a brace. The resistance function of Pm13 is validated through transient and stable transgenic complementation assays. Transient over-expression analyses in Nicotiana benthamiana leaves and wheat protoplasts reveal that the fragment Brace-Kinase122-476 of MLKL-K is capable of inducing cell death, which is dependent on a functional kinase domain and the three α-helices in the brace region close to the N-terminus of the kinase domain.

[Whole exome sequencing analysis of 37 fetuses with cardiac abnormalities].

OBJECTIVE: To explore the genetic etiology of fetuses with congenital heart disease (CHD) through whole exome sequencing (WES). METHODS: Thirty seven fetuses identified with CHD by prenatal ultrasonography but with negative results by chromosomal microarray analysis (CMA) at Jinhua Maternal and Child Health Care Hospital from January 2020 to June 2022 were selected as the study subjects, for whom WES was carried out. RESULTS: WES and Sanger sequencing had detected 6 pathogenic or likely pathogenic variants, and 6 variants with unknown clinical significance. The variants had involved 15 loci within 11 genes, in addition with one copy number variation. CONCLUSION: WES can increase the detection rate for genetic abnormalities among fetuses with CHD, which can facilitate the prenatal diagnosis, evaluation of prognosis and genetic counseling for the couples.

Protein-losing enteropathy as a new phenotype in atypical hemolytic uremic syndrome caused by CD46 gene mutation.

BACKGROUND: Atypical hemolytic uremic syndrome (aHUS) is a life-threatening thrombotic microangiopathy. Genetic defects in the alternative complement (AP) pathway have been identified in 60-70% of individuals. Eculizumab is recommended as a first-line therapy. METHODS: We collected the clinical data of a pediatric patient with aHUS accompanied by protein-losing enteropathy (PLE). Genetic testing was performed. Related literature on aHUS combined with PLE was reviewed. RESULTS: A 15-year-old Chinese girl was diagnosed with aHUS at 3.7 years of age and experienced five episodes; her symptoms completely resolved with plasma treatment. Severe gastrointestinal symptoms and hypoalbuminemia presented after the first episode, and PLE was diagnosed. A novel homozygous CD46 variant was identified, and FACS revealed significantly decreased CD46 expression. She presented at a recent relapse with persistent GI symptoms and headache and progressed to chronic kidney failure; peritoneal dialysis was initiated. Eculizumab was given 8 months after the last recurrence. Surprisingly, PLE was cured. Afterward, dialysis was discontinued, and eGFR recovered to 44.8 ml/min/1.73 m2. A review of the literature indicated that PLE with thrombosis was caused by CD55 variants via hyperactivation of the AP system. We report an aHUS patient with PLE caused by CD46 variants. Symptoms of both PLE and aHUS were significantly alleviated in our patient and patients with CD55 variants treated with eculizumab, indicating that PLE was a new symptom of aHUS in our patient with a CD46 variant. CONCLUSIONS: Our case expands the phenotype of aHUS caused by a CD46 mutation and provides evidence of the efficacy of eculizumab after a long phase of chronic kidney failure.

Integrating single-cell transcriptomics and machine learning to predict breast cancer prognosis: A study based on natural killer cell-related genes.

Breast cancer (BC) is the most commonly diagnosed cancer in women globally. Natural killer (NK) cells play a vital role in tumour immunosurveillance. This study aimed to establish a prognostic model using NK cell-related genes (NKRGs) by integrating single-cell transcriptomic data with machine learning. We identified 44 significantly expressed NKRGs involved in cytokine and T cell-related functions. Using 101 machine learning algorithms, the Lasso + RSF model showed the highest predictive accuracy with nine key NKRGs. We explored cell-to-cell communication using CellChat, assessed immune-related pathways and tumour microenvironment with gene set variation analysis and ssGSEA, and observed immune components by HE staining. Additionally, drug activity predictions identified potential therapies, and gene expression validation through immunohistochemistry and RNA-seq confirmed the clinical applicability of NKRGs. The nomogram showed high concordance between predicted and actual survival, linking higher tumour purity and risk scores to a reduced immune score. This NKRG-based model offers a novel approach for risk assessment and personalized treatment in BC, enhancing the potential of precision medicine.

The underlying mechanisms by which boron mitigated copper toxicity in Citrus sinensis leaves revealed by integrated analysis of transcriptome, metabolome, and physiology.

Both copper (Cu) excess and boron (B) deficiency are often observed in some citrus orchard soils. The molecular mechanisms by which B alleviates excessive Cu in citrus are poorly understood. Seedlings of sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) were treated with 0.5 (Cu0.5) or 350 (Cu350 or Cu excess) µM CuCl2 and 2.5 (B2.5) or 25 (B25) µM HBO3 for 24 weeks. Thereafter, this study examined the effects of Cu and B treatments on gene expression levels revealed by RNA-Seq, metabolite profiles revealed by a widely targeted metabolome, and related physiological parameters in leaves. Cu350 upregulated 564 genes and 170 metabolites, and downregulated 598 genes and 58 metabolites in leaves of 2.5 µM B-treated seedlings (LB2.5), but it only upregulated 281 genes and 100 metabolites, and downregulated 136 genes and 40 metabolites in leaves of 25 µM B-treated seedlings (LB25). Cu350 decreased the concentrations of sucrose and total soluble sugars, and increased the concentrations of starch, glucose, fructose, and total nonstructural carbohydrates (TNC) in LB2.5, but it only increased the glucose concentration in LB25. Further analysis demonstrated that B addition reduced the oxidative damage and alterations in primary and secondary metabolisms caused by Cu350; and alleviated the impairment of Cu350 to photosynthesis and cell wall metabolism, thus improving leaf growth. LB2.5 exhibited some adaptive responses to Cu350 to meet the increasing need for the dissipation of excessive excitation energy (EEE) and the detoxification of reactive oxygen species (reactive aldehydes) and Cu. Cu350 increased photorespiration, xanthophyll cycle-dependent thermal dissipation, nonstructural carbohydrate accumulation, and secondary metabolite biosynthesis and abundances; and upregulated tryptophan metabolism and related metabolite abundances, and some antioxidant-related gene expression, and some antioxidant abundances. Additionally, this study identified some metabolic pathways, metabolites, and genes that might lead to Cu tolerance in leaves.

Homologous Tumor Cell-Derived Biomimetic Nano-Trojan Horse Integrating Chemotherapy with Genetherapy for Boosting Triple-Negative Breast Cancer Therapy.

Triple-negative breast cancer (TNBC) is a subtype of breast cancer that carries the worst prognosis and lacks specific therapeutic targets. To achieve accurate "cargos" delivery at the TNBC site, we herein constructed a novel biomimetic nano-Trojan horse integrating chemotherapy with gene therapy for boosting TNBC treatment. Briefly, we initially introduce the diselenide-bond-containing organosilica moieties into the framework of mesoporous silica nanoparticles (MONs), thereby conferring biodegradability to intratumoral redox conditions in the obtained MONSe. Subsequently, doxorubicin (Dox) and therapeutic miR-34a are loaded into MONSe, thus achieving the combination of chemotherapy and gene-therapy. After homologous tumor cell membrane coating, the ultimate homologous tumor cell-derived biomimetic nano-Trojan horse (namely, MONSe@Dox@miR-34a@CM) can selectively enter the tumor cells in a stealth-like fashion. Notably, such a nanoplatform not only synergistically eradicated the tumor but also inhibited the proliferation of breast cancer stem-like cells (BCSCs) in vitro and in vivo. With the integration of homologous tumor cell membrane-facilitated intratumoral accumulation, excellent biodegradability, and synergistic gene-chemotherapy, our biomimetic nanocarriers hold tremendous promise for the cure of TNBC in the future.

Ozone modification of waxy rice starch nanocrystals: Effects on the multi-scale structural and surface properties.

The rich active hydroxyl groups on starch nanocrystals (SNC) surface limits its dispersion and stability in the aqueous phase. To address this issue, ozone modification for 0 (SNC), 0.5 (SNC-1), 1 (SNC-2), 1.5 (SNC-3), and 2 h (SNC-4) as compared to conventionally chemical methods was applied to functionally modify the SNC. The impact of ozone treatment on the structural and surface characteristics of waxy rice starch nanocrystals. The findings revealed that longer ozone treatment durations favored the formation of carbonyl groups in starch molecules. Initially, ozone oxidized the hydroxyl group of the macromolecule. Once the carbonyl groups formed, the cross-linking reaction occurred among starch nanocrystals through condensation reactions, leading to the increasing molecular orderliness. X-ray photoelectron spectroscopy, X-ray diffraction and Small-angle X-ray scattering analyses of SNC-2 supported this finding with a reduced O/C ratio, and implied that surface oxidation did not alter the crystal type but rather enhanced molecular hydration in an aqueous system, leading to increased interfacial thickness and fractal dimension. Additionally, ozone oxidation improved surface properties such as charge and hydrophobicity. Oxidized SNC also exhibited altered gelatinization properties due to surface degradation. This study offers a promising strategy for enhancing SNC surface properties, crucial for food science applications.

Efficacy and Safety of Anlotinib in EGFR-Positive Patients with Advanced Lung Adenocarcinoma Compared with Chemotherapy: A Retrospective Study.

There are no standard third-line or beyond treatments for patients with driver mutation-positive advanced lung adenocarcinoma (LUAD). Anlotinib was approved as a third-line multitarget drug in China in 2018. Limited data are available regarding the efficacy and safety of anlotinib compared with chemotherapy. To investigate the efficacy and safety of anlotinib compared with traditional chemotherapy in patients with epidermal growth factor receptor (EGFR)-positive advanced LUAD. We conducted a retrospective study of 83 EGFR mutation-positive patients with advanced LUAD between 2011 and 2022. Progression-free survival (PFS) and overall survival (OS) were the primary endpoints, whereas the objective response rate (ORR) and disease control rate (DCR) were the secondary endpoints. Anlotinib-related adverse events (AEs) were recorded to evaluate the safety of anlotinib. 39 patients with LUAD received anlotinib and 44 patients with LUAD received chemotherapy were enrolled in the study. Patients treated with anlotinib exhibited longer PFS (11.2 vs 4.5 months, P < .01) and OS (18.8 vs 15.8 months, P < .05) than patients treated with chemotherapy. There were no significant differences in ORR (7.9% vs 20.5%, P = .129) or DCR (100% vs 93.2%, P = .120) between the two groups. Anlotinib-related AEs grading 3-4 level were observed in 2 (5.1%) patients, no anlotinib-related death was recorded. Cox regression analyses of PFS and OS showed that brain metastases and age < 30 years at diagnosis had negative effects on clinical outcomes. Anlotinib is effective and safe in patients with EGFR-positive advanced LUAD. Patients without brain metastases had better clinical outcomes.

[Testis-sparing microsurgery for benign testis tumor: A report of 16 cases].

OBJECTIVE: To investigate the safety and clinical effect of testis-sparing microsurgery (TSMS) in the treatment of benign testis tumor (BTT). METHODS: We retrospectively analyzed the clinical data on 16 cases of BTT treated in the Department of Andrology of the Affiliated Hospital of Qingdao University from October 2020 to February 2023. The median age of the patients was 23 years. All the tumors were unilateral, 7 in the left and 9 in the right side, with a median diameter of 1.85 cm (1.0－3.5 cm). The patients all underwent color Doppler flow imaging (CDFI), MRI, semen analysis and examination of serum T, alpha-fetoprotein (AFP), human chorionic gonadotropin (HCG) and lactate dehydrogenase (LDH), followed by TSMS. The boundaries between the tumors and normal testis tissue were accurately identified under the microscope, and the tumors and the adjacent normal testis tissue 2 mm from their margins were excised completely. Bipolar coagulation forceps were used for wound hemostasis to maximally preserve the normal testis tissue. The resected specimens were subjected to fast frozen pathology intraoperatively, and the patients were followed up for 14－40 months by regular scrotal CDFI, MRI and examinations of serum T and semen parameters. RESULTS: The levels of serum T, AFP, HCG and LDH and semen parameters were all within the normal range preoperatively. TSMS were successfully completed in all the cases, and all were pathologically confirmed as BTT according to the latest edition of WHO Classification of Tumors: Urinary and Male Genital Tumors. CDFI showed normal blood supply within the testis tissue at 1 month after surgery. No signs of intra-testicular tumor residue, recurrence or metastasis, nor significant changes in the levels of serum T, AFP, HCG or LDH or semen parameters were observed during the follow-up as compared with the baseline. Natural conception was achieved in 2 cases at 16 and 18 months respectively after surgery. CONCLUSION: BTT can be differentially diagnosed by CDFI and MRI before surgery and confirmed by histopathology. TSMS can achieve complete excision of the tumor, maximal sparing of the normal testis tissue and thereby effective preservation of male fertility.

An Algorithm for Automated Measurement of Kinetic Tremor Magnitude Using Digital Spiral Drawings.

Introduction: Essential tremor is a common movement disorder. Numerous validated clinical rating scales exist to quantify essential tremor severity by employing rater-dependent visual observation but have limitations, including the need for trained human raters and the lack of precision and sensitivity compared to technology-based objective measures. Other continuous objective methods to quantify tremor amplitude have been developed, but frequently provide unitless measures (e.g., tremor power), limiting real-world interpretability. We propose a novel algorithm to measure kinetic tremor amplitude using digital spiral drawings, applying the V3 framework (sensor verification, analytical validation, and clinical validation) to establish reliability and clinical utility. Methods: Archimedes spiral drawings were recorded on a digitizing tablet from participants (n = 7) enrolled in a randomized placebo control double-blinded crossover pilot trial evaluating the efficacy of oral cannabinoids in reducing essential tremor. We developed an algorithm to calculate the mean and maximum tremor amplitude derived from the spiral tracings. We compared the digitally measured tremor amplitudes to manual measurement to evaluate sensor reliability, determined the test-retest reliability of the digital output across two short-interval repeated measures, and compared the digital measure to kinetic tremor severity graded using The Essential Tremor Rating Assessment Scale (TETRAS) score for spiral drawings. Results: This algorithm for automated assessment of kinetic tremor amplitude from digital spiral tracings demonstrated a high correlation with manual spot measures of tremor amplitude, excellent test-retest reliability, and a high correlation with human ratings of the TETRAS score for spiral drawing severity when the tremor severity was rated "slight tremor" or worse. Discussion: This digital measure provides a simple and clinically relevant evaluation of kinetic tremor amplitude that shows promise as a potential future endpoint for use in clinical trials of essential tremor.

USP11 promotes renal tubular cell pyroptosis and fibrosis in UUO mice via inhibiting KLF4 ubiquitin degradation.

The pyroptosis of renal tubular epithelial cells leads to tubular loss and inflammation and then promotes renal fibrosis. The transcription factor Krüppel-like factor 4 (KLF4) can bidirectionally regulate the transcription of target genes. Our previous study revealed that sustained elevation of KLF4 is responsible for the transition of acute kidney injury (AKI) into chronic kidney disease (CKD) and renal fibrosis. In this study, we explored the upstream mechanisms of renal tubular epithelial cell pyroptosis from the perspective of posttranslational regulation and focused on the transcription factor KLF4. Mice were subjected to unilateral ureteral obstruction (UUO) surgery and euthanized on D7 or D14 for renal tissue harvesting. We showed that the pyroptosis of renal tubular epithelial cells mediated by both the Caspase-1/GSDMD and Caspase-3/GSDME pathways was time-dependently increased in UUO mouse kidneys. Furthermore, we found that the expression of the transcription factor KLF4 was also upregulated in a time-dependent manner in UUO mouse kidneys. Tubular epithelial cell-specific Klf4 knockout alleviated UUO-induced pyroptosis and renal fibrosis. In Ang II-treated mouse renal proximal tubular epithelial cells (MTECs), we demonstrated that KLF4 bound to the promoter regions of Caspase-3 and Caspase-1 and directly increased their transcription. In addition, we found that ubiquitin-specific protease 11 (USP11) was increased in UUO mouse kidneys. USP11 deubiquitinated KLF4. Knockout of Usp11 or pretreatment with the USP11 inhibitor mitoxantrone (3 mg/kg, i.p., twice a week for two weeks before UUO surgery) significantly alleviated the increases in KLF4 expression, pyroptosis and renal fibrosis. These results demonstrated that the increased expression of USP11 in renal tubular cells prevents the ubiquitin degradation of KLF4 and that elevated KLF4 promotes inflammation and renal fibrosis by initiating tubular cell pyroptosis.

CD161+CD127+CD8+ T cell subsets can predict the efficacy of anti-PD-1 immunotherapy in non-small cell lung cancer with diabetes mellitus.

The role of CD161+CD127+CD8+ T cells in non-small cell lung cancer (NSCLC) patients with diabetes remains unexplored. This study determined the prevalence, phenotype, and function of CD8+ T cell subsets in NSCLC with diabetes. We recruited NSCLC patients (n = 436) treated with anti-PD-1 immunotherapy as first-line treatment. The progression-free survival (PFS), overall survival (OS), T cells infiltration, and peripheral blood immunological characteristics were analyzed in NSCLC patients with or without diabetes. NSCLC patients with diabetes exhibited shorter PFS and OS (p = 0.0069 and p = 0.012, respectively) and significantly lower CD8+ T cells infiltration. Mass cytometry by time-of-flight (CyTOF) showed a higher percentage of CD161+CD127+CD8+ T cells among CD8+T cells in NSCLC with diabetes before anti-PD-1 treatment (p = 0.0071) than that in NSCLC without diabetes and this trend continued after anti-PD-1 treatment (p = 0.0393). Flow cytometry and multiple-immunofluorescence confirmed that NSCLC with diabetes had significantly higher CD161+CD127+CD8+ T cells to CD8+T cells ratios than NSCLC patients without diabetes. The RNA-sequencing analysis revealed immune-cytotoxic genes were reduced in the CD161+CD127+CD8+ T cell subset compared to CD161+CD127-CD8+ T cells in NSCLC with diabetes. CD161+CD127+CD8+ T cells exhibited more T cell-exhausted phenotypes in NSCLC with diabetes. NSCLC patients with diabetes with ≥ 6.3% CD161+CD127+CD8+ T cells to CD8+T cells ratios showed worse PFS. These findings indicate that diabetes is a risk factor for NSCLC patients who undergo anti-PD-1 immunotherapy.CD161+CD127+CD8+ T cells could be a key indicator of a poor prognosis in NSCLC with diabetes. Our findings would help in advancing anti-PD-1 therapy in NSCLC patients with diabetes.

COVID-19 vaccination and long COVID among 50 years older and above European: The role of chronic multimorbidity.

BACKGROUND AND AIMS: We aimed to explore the association between coronavirus disease-19 (COVID-19) vaccination and long COVID according to the status of chronic multimobidity. METHODS: A total of 1913 participants were recruited in the cross-sectional study on the basis of the Survey of Health and Retirement in Europe. COVID-19 vaccination was defined as vaccination within the last 12 months. Chronic multimorbidity was defined as history of 2 + chronic disease. The study outcome was long COVID during the 12-month follow-up. Multivariable logistic models were performed to estimate the influence of chronic multimorbidity on the association of vaccination with long COVID. Net reclassification improvement (NRI) and integrated discrimination improvement (IDI) were calculated. RESULTS: Chronic multimorbidity significantly modified the association of COVID-19 vaccination with long COVID (Pinteraction = 0.024). The rates of study outcome were significantly lower among vaccinated participants in the chronic multimorbidity subgroup, but not in the other subgroup. Multivariable odds ratios (95 % confidence intervals) of study outcome for unvaccination vs. vaccination were 1.494 (1.013-2.203) in those with multimorbidity and 0.915 (0.654-1.280) in those without multimorbidity, respectively. Adding COVID-19 vaccination to a model containing conventional risk factors significantly improved risk reclassification for study outcome among those with chronic multimobidity (continuous NRI was 25.39 % [P = 0.002] and IDI was 0.42 % [P = 0.075]) CONCLUSION: An inverse association of COVID-19 vaccination with long COVID was found among participants with chronic multimorbidity, but not among those without chronic multimorbidity. Chronic multimorbidity might expand the influence of unvaccination on developing long COVID among European aged ≥50 years.

The relationship between psoriasis and vitiligo: From a comprehensive study.

BACKGROUND: Both psoriasis and vitiligo are autoimmune skin diseases. Previous observational studies have indicated a relationship between the two conditions, and simultaneous onset of both diseases poses increased health risks to patients. However, limited research has explored the causal relationship between psoriasis and vitiligo. OBJECTIVES: To investigate whether a causal association exists between psoriasis and vitiligo. METHODS: A case of Chinese patients diagnosed with psoriasis and vitiligo has been reported. Transcriptome sequencing was performed on normal, psoriasis, vitiligo, and co-morbid skin tissues of the patients, and single-cell transcriptome sequencing was conducted on the co-morbid skin tissues. A comprehensive Mendelian randomization analysis of Genome-wide association studies (GWAS) was performed on a cohort of 261 018 European individuals with psoriasis from the IEU Open GWAS Project and vitiligo from the National Institutes of Health (NIH) Database of Genotypes and Phenotypes. RESULTS: Case report and transcriptome results showed that skin tissue with vitiligo combined with psoriasis exhibited both vitiligo and psoriasis. Single-cell transcriptome sequencing results showed that in comparison to normal skin and psoriatic skin, the proportions of CD8+ T cells, natural killer cells, naive T cells, T helper cells 17, regulatory T cells, conventional type 1 dendritic cells, Conventional type 2 dendritic cells, and plasmacytoid dendritic cells were all increased in skin tissue with vitiligo combined with psoriasis. Mendelian randomization analysis included 4510 patients with psoriasis and 4680 patients with vitiligo. The results showed no causal relationship between vitiligo and psoriasis in the forward direction (p = 0.192; odds ratio [OR], 1.059; 95% confidence interval [CI], 0.971-1.155) or in the reverse direction (p = 0.459; OR, 0.927; 95% CI, 0.757-1.134). CONCLUSIONS: This study suggests that the association between psoriasis and vitiligo may be closely related to immunity, however, Mendelian randomization studies do not support a causal relationship. These findings hold significant implications for clinicians aiming to enhance their understanding and treatment approaches for psoriasis and vitiligo.

Duzhong Fang ameliorates cognitive impairment of Parkinsonian mice by suppressing neuronal apoptotic pathway.

Parkinson's disease (PD) is a complex multisystem neurodegenerative disease, and cognitive impairment is a common symptom in the trajectory of PD. Duzhong Fang (DZF) consists of Eucommia ulmoides, Dendrobium, Rehmanniae Radix, and Dried Ginger. Our previous study showed that DZF improves motor deficits in mice. However, whether DZF can ameliorate cognitive impairment in PD has not been reported. In this study, we established mice models of PD induced by rotenone and examined the effect of DZF on cognitive impairment in Parkinson's disease (PD-CI). The results confirmed that DZF treatment not only significantly improved the motor deficits in PD mice and decreased the loss of dopaminergic neurons, but also had significant effects in improving cognitive impairment. We further integrate serum metabolome and network pharmacology to explore the mechanisms by which DZF improves PD-CI. The results revealed that DZF can treat PD-CI by regulating sphingolipid metabolism to inhibit neuronal apoptotic pathway. In conclusion, preliminary studies confirmed that DZF contributes to the improvement of cognitive ability in PD, and our results provide a potential drug for the clinical treatment of PD and a theoretical foundation for DZF in clinical application.

Unidirectional guided-wave-driven metasurfaces for arbitrary wavefront control.

Metasurfaces are capable of fully reshaping the wavefronts of incident beams in desired manners. However, the requirement for external light excitation and the resonant nature of their meta-atoms, make challenging their on-chip integration. Here, we introduce the concept and design of a fresh class of metasurfaces, driven by unidirectional guided waves, capable of arbitrary wavefront control based on the unique dispersion properties of unidirectional guided waves rather than resonant meta-atoms. Upon experimentally demonstrating the feasibility of our designs in the microwave regime, we numerically validate the introduced principle through the design of several microwave meta-devices using metal-air-gyromagnetic unidirectional surface magneto-plasmons, agilely converting unidirectional guided modes into the wavefronts of 3D Bessel beams, focused waves, and controllable vortex beams. We, further, numerically demonstrate sub-diffraction focusing, which is beyond the capability of conventional metasurfaces. Our unfamiliar yet practical designs may enable full, broadband manipulation of electromagnetic waves on deep subwavelength scales.

Analysis of clinicopathological characteristics and prognosis on primary gastric adenosquamous carcinoma.

Primary gastric adenosquamous carcinoma (PGASC) is a rare type of gastric cancer with limited research and poorly understood clinicopathological features. This study investigated the clinicopathological features and outcomes of PGASC. Patients with PGASC from Union Hospital, Tongji Medical College, Huazhong University of Science and Technology and from the published literature were enrolled in this study. Survival curves were generated using the Kaplan-Meier method, and prognostic factors were identified through Cox proportional hazards regression models. This study identified 76 eligible cases of PGASC, with 45 cases from published literature and 31 from our center. The most prevalent symptoms were abdominal pain and dysphagia, with a median age of 62 years (range: 29-84 years). The primary lesions were predominantly in the proximal stomach, with a median tumor size of 6.5 cm (range: 1.5-16.0 cm). Tumor stages II, III, and IV were detected in 12 (16.7%), 43 (59.7%), and 17 (23.6%) patients, respectively. Most tumors were poorly differentiated in both the squamous cell carcinoma (SCC) component and adenocarcinoma (AC) component. The median survival time was 17 months (range: 2-122 months). The 1, 3, and 5-year overall survival (OS) was 60.7%, 31.1%, and 24.1%, respectively. Multivariate analysis revealed that OS was independently predicted by the proportion of SCC component, differentiation of AC component, and tumor stage. PGASC is a rare disease with a poor prognosis. A high proportion of SCC components, low differentiated AC components, and advanced tumor were associated with worse survival in patients with PGASC. Adjuvant therapy did not improve survival time.

Adaptive Responses of Hormones to Nitrogen Deficiency in Citrus sinensis Leaves and Roots.

Some citrus orchards in China often experience nitrogen (N) deficiency. For the first time, targeted metabolomics was used to examine N-deficient effects on hormones in sweet orange (Citrus sinensis (L.) Osbeck cv. Xuegan) leaves and roots. The purpose was to validate the hypothesis that hormones play a role in N deficiency tolerance by regulating root/shoot dry weight ratio (R/S), root system architecture (RSA), and leaf and root senescence. N deficiency-induced decreases in gibberellins and indole-3-acetic acid (IAA) levels and increases in cis(+)-12-oxophytodienoic acid (OPDA) levels, ethylene production, and salicylic acid (SA) biosynthesis might contribute to reduced growth and accelerated senescence in leaves. The increased ethylene formation in N-deficient leaves might be caused by increased 1-aminocyclopropanecarboxylic acid and OPDA and decreased abscisic acid (ABA). N deficiency increased R/S, altered RSA, and delayed root senescence by lowering cytokinins, jasmonic acid, OPDA, and ABA levels and ethylene and SA biosynthesis, increasing 5-deoxystrigol levels, and maintaining IAA and gibberellin homeostasis. The unchanged IAA concentration in N-deficient roots involved increased leaf-to-root IAA transport. The different responses of leaf and root hormones to N deficiency might be involved in the regulation of R/S, RSA, and leaf and root senescence, thus improving N use efficiency, N remobilization efficiency, and the ability to acquire N, and hence conferring N deficiency tolerance.

Acid-modified biomass-based N-doped O-rich hierarchical porous carbon as a high-performance electrode for supercapacitors.

In contemporary society, the conversion and efficient utilization of waste biomass and its derivatives are of great significance. Carbonized wood (CW) is an easily accessible and cost-effective green resource, but it has limitations as an electrode material due to its low specific surface area, limited active sites and poor conductivity. Therefore, it is crucial to improve the performance of biomass-based materials by using activation, heteroatom doping and modification methods to enhance the specific surface area and active sites. In this study, we developed acid-modified urea-doped activated carbonized wood (AUACW) with a three-dimensional (3D) porous structure and porosity, achieving a high specific surface area of 1321.3 m2 g-1. In addition, the degree of graphitization (ID/IG = 1.0) provides good conductivity and a large number of active sites, which are conducive to charge transfer and ion diffusion. The increase of nitrogen and oxygen elements enhances the surface wettability of the material and provides additional pseudocapacitance. The specific capacitance of AUACW reaches 435.84 F g-1 at 0.8 A g-1 with a 93.6% capacitance retention after 10 000 cycles in a 1 M KOH electrolyte. More attractively, a symmetrical supercapacitor (SSC) based on AUACW delivers an energy density of 22.61 W h kg-1 at a power density of 533.26 W kg-1. This work demonstrates the promising potential of utilizing waste biomass to develop green and valuable carbon materials for supercapacitors.