Transcriptome-wide Interrogation of the Functional Intronome by Spliceosome Profiling.

Full understanding of eukaryotic transcriptomes and how they respond to different conditions requires deep knowledge of all sites of intron excision. Although RNA sequencing (RNA-seq) provides much of this information, the low abundance of many spliced transcripts (often due to their rapid cytoplasmic decay) limits the ability of RNA-seq alone to reveal the full repertoire of spliced species. Here, we present "spliceosome profiling," a strategy based on deep sequencing of RNAs co-purifying with late-stage spliceosomes. Spliceosome profiling allows for unambiguous mapping of intron ends to single-nucleotide resolution and branchpoint identification at unprecedented depths. Our data reveal hundreds of new introns in S. pombe and numerous others that were previously misannotated. By providing a means to directly interrogate sites of spliceosome assembly and catalysis genome-wide, spliceosome profiling promises to transform our understanding of RNA processing in the nucleus, much as ribosome profiling has transformed our understanding mRNA translation in the cytoplasm.

GPMeta: a GPU-accelerated method for ultrarapid pathogen identification from metagenomic sequences.

Metagenomic sequencing (mNGS) is a powerful diagnostic tool to detect causative pathogens in clinical microbiological testing owing to its unbiasedness and substantially reduced costs. Rapid and accurate classification of metagenomic sequences is a critical procedure for pathogen identification in dry-lab step of mNGS test. However, clinical practices of the testing technology are hampered by the challenge of classifying sequences within a clinically relevant timeframe. Here, we present GPMeta, a novel GPU-accelerated approach to ultrarapid pathogen identification from complex mNGS data, allowing users to bypass this limitation. Using mock microbial community datasets and public real metagenomic sequencing datasets from clinical samples, we show that GPMeta has not only higher accuracy but also significantly higher speed than existing state-of-the-art tools such as Bowtie2, Bwa, Kraken2 and Centrifuge. Furthermore, GPMeta offers GPMetaC clustering algorithm, a statistical model for clustering and rescoring ambiguous alignments to improve the discrimination of highly homologous sequences from microbial genomes with average nucleotide identity >95%. GPMetaC exhibits higher precision and recall rate than others. GPMeta underlines its key role in the development of the mNGS test in infectious diseases that require rapid turnaround times. Further study will discern how to best and easily integrate GPMeta into routine clinical practices. GPMeta is freely accessible to non-commercial users at https://github.com/Bgi-LUSH/GPMeta.

Apatinib Plus Toripalimab (Anti-PD1 Therapy) as Second-Line Therapy in Patients With Advanced Gastric or Esophagogastric Junction Cancer: Results From a Randomized, Open-Label Phase II Study.

BACKGROUND: This study aimed to assess the activity of apatinib plus toripalimab in the second line for patients with advanced gastric or esophagogastric junction cancer (GC/EGJC). METHODS: In this open-label, phase II, randomized trial, patients with advanced GC/EGJC who progressed after first-line chemotherapy were enrolled and received 250 mg apatinib per day plus 240 mg toripalimab on day 1 per 3 weeks (arm A) or physician's choice of chemotherapy (PC, arm B). The primary endpoint of this study was the 1-year survival rate. Progression-free survival (PFS), overall survival (OS), overall response rate (ORR), and safety were assessed as secondary endpoints. RESULTS: Twenty-five patients received apatinib plus toripalimab while 26 were enrolled in arm B. The 1-year survival rates of the 2 groups were 43.3% and 42.3%, respectively (P = .903). The PFS was 2.77 versus 2.33 months (P = .660). The OS was 8.30 versus 9.88 months (P = .539). An objective response was reported in 20.0% of patients in arm A compared to 26.9% in arm B (P = .368), respectively. A total of 6 (24.0%) patients experienced adverse events of grade ≥ 3 in arm A, while 9 (34.6%) patients suffered from adverse events of grade ≥ 3 in arm B. No drug-related deaths occurred in either group. CONCLUSION: Toripalimab plus apatinib treatment in second-line therapy of advanced GC/EGJC showed manageable toxicity but did not improve clinical outcomes relative to PC treatment (ClinicalTrials.gov Identifier: NCT04190745).

Methane pulse spray and irrigation promote seed germination and seedling growth of common vetch.

BACKGROUND: Grazing livestock emits methane through rumen intestinal activity, however, its impact on plant growth in grassland while grazing still has not been explored in detail. Therefore, the study examined the effects of methane pulse spray (MPS), according to grazing intensity, at four grazing intensities (0, 3.6, 5.0, and 6.5 sheep·hm- 2 yr- 1) on seed germination and seedling growth of common vetch (Vicia sativa), while two irrigation rates (35 and 53 ml d- 1) were employed to simulate the precipitation. RESULTS: The study revealed significant interactions between MPS and irrigation rate on seed germination and seedling growth parameters. Under moderate MPS intensities (0.74 and 1.04 mol m- 2), seed germination rate, potential, index, and vigor index improved, especially at higher irrigation rates (53 ml d- 1). Conversely, excessive MPS (1.33 mol m- 2) inhibited particularly at the germination rate and growth,. The seedling growth dynamics fitted a logistic model, with MPS advancing the rapid growth phase and increasing maximum growth rates. CONCLUSIONS: This study demonstrates that low to moderate levels of MPS from ruminants can promote seed germination and seedling growth of common vetch, while excessive MPS inhibits these processes. Irrigation enhances plant sensitivity to MPS, with wetter conditions (620 mm yr- 1) facilitating a more pronounced response. The findings introduce a new model elucidating plant responses to external perturbations, which can inform grazing management strategies in diverse ecosystems. In wetter regions, moderate grazing intensities may leverage MPS benefits, while arid regions require careful grazing regulation to maintain grassland-livestock balance.

High-Performance Electro-optical Dual-Mode Color-Changing and Energy Storage Device Based on Mo-Doped WO3 and TiO2/NiO Thin Films.

Under optical and electrical control, a multifunctional electro-optical dual-control color-changing and energy storage device not only realizes fast color conversion but also achieves good energy storage performance. In this work, Mo-doped WO3 (Mo-WO3) films were prepared by a one-step hydrothermal method, among which the 2 at. % Mo-doped WO3 film has the best electrochromic and energy storage performance. Meanwhile, TiO2/NiO composite films were prepared by the hydrothermal method and electrodeposition method. The TiO2/NiO/N719 photoanode was prepared by the dip-dyeing method on the TiO2/NiO composite film. The results show that the TiO2/NiO-10s/N719 composite film has excellent photoelectric conversion and energy storage properties. Finally, choosing Mo-WO3 as the cathode and the TiO2/NiO/N719 film as the anode, a multifunctional electro-optical dual-control Mo-WO3@TiO2/NiO/N719 color-changing and energy storage device was constructed. Under electrical control, it shows a fast color switching rate (the coloring/bleaching time is 4.1/2.9 s), excellent coloration efficiency (62.1 cm2/C), obviously improved area capacitance (90.4 mF/cm2), and excellent cycle stability. Under optical control, it shows a shortened optical response time (the coloring/bleaching is 70.3/158.9 s), excellent coloration efficiency (58.2 cm2/C), better area capacitance (51.1 mF/cm2), and excellent photoelectric conversion efficiency.

The combination of tetramethylpyrazine and vitamin A acid in the treatment of skin photoaging by activating the HIF-1α pathway.

Skin photoaging is a skin degenerative disease that causes patients to develop malignant tumors. The existing clinical treatment of photoaging has limitations. This greatly reduces the recovery rate of photoaging patients. Studies have confirmed that Ligusticum wallichii Franch (LWF) monomer tetramethylpyrazine (TMP) alleviates various skin diseases. The combination of traditional Chinese medicine and Western medicine helps with this process. Our research aimed to explore the specific treatment mode and molecular mechanism of TMP in treating skin photoaging. CCK-8 assays were used to evaluate the activity and toxicity of HaCaT cells. ß-galactosidase aging, Carbonyl compound and nitrosylated tyrosine assays were used to analyze the aging of HaCaT cells. ROS assays and ELISA were used to analyze the enrichment of ROS. The molecular docking experiment analyzed the binding of TMP and HIF-1α. qRT-PCR and Western blot were used to detect the activation of skin aging-related pathways. HE staining was used to analyze the thickness of the stratum corneum skin on the back skin of mice. 200µg/L LWF alleviates cellular photoaging and mouse skin photoaging by reducing ROS enrichment. Its monomer TMP plays an important role in this process. The combination of TMP and HIF-1α accelerates the degradation of ROS by activating the Nrf2/ARE signaling pathway. This process reduces the apoptosis of cells damaged by light. In addition, we also found that the combination of TMP and retinoic acid (RA) is more beneficial for the treatment of skin damage caused by light in mice. The combination therapy of TMP and RA alleviates skin oxidative stress response through overexpression of HIF-1α. This plan is beneficial for the treatment of skin photoaging.

A study of macroinvertebrate community structure and diversity in response to land use type in the Yiluo River Basin.

Land use types have a significant impact on river ecosystems. The Yiluo River is the largest tributary below Xiaolangdi Reservoir in the middle reaches of the Yellow River, and is one of the important water conservation areas in the Yellow River Basin. Studying the ecological status of the Yiluo River under varied land use types in this basin is crucial for both ecological protection and the high-quality development of the Yellow River Basin. This study investigated the impacts of land use types on the macroinvertebrate community and functional structure in the Yiluo River Basin and introduced the concept of the land use health index (LUI). During the survey period, a total of 11,894 macroinvertebrates were collected, and 143 species were identified, belonging to 4 phyla, 7 orders, 22 families, and 75 families. The results showed that LUI had the most significant impact on macroinvertebrate community structure, with substrate type, dry plant weight, total phosphorus, turbidity, and attached algae biomass also playing significant roles in affecting macroinvertebrate communities. The species richness, the Shannon-Wiener index, and the Margalef richness index exhibited a nonlinear positive correlation with LUI of the sampling site, increasing as LUI enhancing and eventually reaching a plateau. Functional richness showed a linear and positive correlation with LUI, increasing with its enhancement, while functional evenness and functional divergence exhibited a nonlinear correlation with LUI. Functional evenness initially increased and then decreased with the enhancement of LUI, while functional divergence decreased with LUI enhancement. This study can provide a scientific reference for river ecological management under various land use scenarios.The Yiluo River is the largest tributary below Xiaolangdi Reservoir in the middle reaches of the Yellow River, and is one of the important water conservation areas in the Yellow River Basin. Studying the ecological status of the Yiluo River under varied land use types in this basin is crucial for both ecological protection and the high-quality development of the Yellow River Basin. This study investigated the impacts of land use types on the macroinvertebrate community and functional structure in the Yiluo River Basin and introduced the concept of the land use health index (LUI). During the survey period, a total of 11,894 macroinvertebrates were collected, and 143 species were identified, belonging to 4 phyla, 7 orders, 22 families, and 75 families. The results showed that LUI had the most significant impact on macroinvertebrate community structure, with substrate type, dry plant weight, total phosphorus, turbidity, and attached algae biomass also playing significant roles in affecting macroinvertebrate communities. The species richness, the Shannon-Wiener index, and the Margalef richness index exhibited a nonlinear positive correlation with LUI of the sampling site, increasing as LUI enhancing and eventually reaching a plateau. Functional richness showed a linear and positive correlation with LUI, increasing with its enhancement, while functional evenness and functional divergence exhibited a nonlinear correlation with LUI. Functional evenness initially increased and then decreased with the enhancement of LUI, while functional divergence decreased with LUI enhancement. This study can provide a scientific reference for river ecological management under various land use scenarios.

Disruption of Cell Membranes and Redox Homeostasis as an Antibacterial Mechanism of Dielectric Barrier Discharge Plasma against Fusarium oxysporum.

Direct barrier discharge (DBD) plasma is a potential antibacterial strategy for controlling Fusarium oxysporum (F. oxysporum) in the food industry. The aim of this study was to investigate the inhibitory effect and mechanism of action of DBD plasma on F. oxysporum. The result of the antibacterial effect curve shows that DBD plasma has a good inactivation effect on F. oxysporum. The DBD plasma treatment severely disrupted the cell membrane structure and resulted in the leakage of intracellular components. In addition, flow cytometry was used to observe intracellular reactive oxygen species (ROS) levels and mitochondrial membrane potential, and it was found that, after plasma treatment, intracellular ROS accumulation and mitochondrial damage were accompanied by a decrease in antioxidant enzyme activity. The results of free fatty acid metabolism indicate that the saturated fatty acid content increased and unsaturated fatty acid content decreased. Overall, the DBD plasma treatment led to the oxidation of unsaturated fatty acids, which altered the cell membrane fatty acid content, thereby inducing cell membrane damage. Meanwhile, DBD plasma-induced ROS penetrated the cell membrane and accumulated intracellularly, leading to the collapse of the antioxidant system and ultimately causing cell death. This study reveals the bactericidal effect and mechanism of the DBD treatment on F. oxysporum, which provides a possible strategy for the control of F. oxysporum.

The RALF1-FERONIA interaction modulates endocytosis to mediate control of root growth in Arabidopsis.

The interaction between the receptor-like kinase (RLK) FERONIA (FER) and the secreted peptide RAPID ALKALINIZATION FACTOR1 (RALF1) is vital for development and stress responses in Arabidopsis Ligand-induced membrane dynamics affect the function of several RLKs, but the effects of the RALF1-FER interaction on the dynamics of FER and the ensuing effects on its functionality are poorly understood. Here, we show that RALF1 modulated the dynamics and partitioning of FER-GFP at the plasma membrane (PM). Moreover, FER was internalized by both clathrin-mediated endocytosis (CME) and clathrin-independent endocytosis (CIE) under steady-state conditions. After RALF1 treatment, FER-GFP internalization was primarily enhanced via the CME pathway, raising FER-GFP levels in the vacuole. RALF1 treatment also modulated trafficking of other PM proteins, such as PIN2-GFP and BRI1-GFP, increasing their vacuolar levels by enhancing their internalization. Importantly, blocking CME attenuated RALF1-mediated root growth inhibition independently of RALF1-induced early signaling, suggesting that the RALF1 can also exert its effects via the CME pathway. These findings reveal that the RALF1-FER interaction modulates plant growth and development, and this might also involve endocytosis of PM proteins.

CAR modulates plasma membrane nano-organization and immune signaling downstream of RALF1-FERONIA signaling pathway.

In Arabidopsis, the receptor-like kinase (RLK) FERONIA (FER) senses peptide ligands in the plasma membrane (PM), modulates plant growth and development, and integrates biotic and abiotic stress signaling for downstream adaptive responses. However, the molecular interplay of these diverse processes is largely unknown. Here, we show that FER, the receptor of Rapid Alkalinization Factor 1 (RALF1), physically interacts with C2 domain ABA-related (CAR) proteins to control the nano-organization of the PM. During this process, the RALF1-FER pathway upregulates CAR protein translation, and then more CAR proteins are recruited to the PM. This acts as a rapid feedforward loop that stabilizes the PM liquid-ordered phase. FER interacts with and phosphorylates CARs, thereby reducing their lipid-binding ability and breaking the feedback regulation at later time points. The formation of the flg22-induced FLS2-BAK1 immune complex, which depends on the integrity of FER-containing nanodomains, is impaired in fer and pentuple car14569 mutant. Together, we propose that the FER-CAR module controls the formation of PM nano-organization during RALF signaling through a self-contained amplifying loop including both positive and negative feedback.

Respiratory depression driven by membrane damage as a mechanism for linalool to inhibit Pseudomonas lundensis and its preservation potential for beef.

AIMS: This study aimed to investigate the mechanism of linalool against Pseudomonas lundensis and its application on beef. METHODS AND RESULTS: Field emission scanning electron microscopy found that linalool exerted antibacterial activity with a minimum inhibitory concentration (MIC) of 1.5 ml l-1 by disrupting cell structure. Loss of cell membrane integrity was monitored due to leakage of nucleic acids and K+. In addition, respiratory depression appeared in Ps. lundensis based on inhibition of enzyme activities including hexokinase (HK), glucose 6-phosphate dehydrogenase (G6PDH), phosphofructokinase (PFK), pyruvate kinase (PK), pyruvate dehydrogenase (PDH), citrate synthase (CS), succinate dehydrogenase (SDH), and malate dehydrogenase (MDH). Subsequently, energy limitation also occurred according to the decrease in ATP content and ATPase activity. Molecular docking confirmed that linalool can combine with enzymes in cell wall (ddlB) and energy synthesis (AtpD) pathways to exert antibacterial effect. Of note, linalool has advantages for beef preservation by delaying quality changes including pH, total volatile basic nitrogen (TVB-N) and total viable count (TVC). CONCLUSIONS: Linalool has significant inhibitory effect on Ps. lundensis, and respiratory depression driven by membrane damage is the main inhibitory mechanism.

Diagnostic performance of noncultural methods for central nervous system aspergillosis.

BACKGROUND: Central nervous system (CNS) aspergillosis is an uncommon but fatal disease, the diagnosis of which is still difficult. OBJECTIVES: We aim to explore the diagnositic performance of noncultural methods for CNS aspergillosis. METHODS: In this retrospective study, all pathologically confirmed rhinosinusitis patients in whom cerebrospinal fluid (CSF) galactomannan (GM) test and metagenomic next-generation sequencing (mNGS) had been performed were included. We evaluated the diagnostic performances of CSF GM optical density indexes (ODI) at different cut-off values and compared performance with mNGS in patients with and without CNS aspergillosis, as well as in patients with different manifestations of CNS aspergillosis. RESULTS: Of the 21 proven and probable cases, one had positive culture result, five had positive mNGS results and 10 had a CSF GM ODI of >0.7. Sample concordance between mNGS and GM test was poor, but best diagnostic performance was achieved by combination of GM test (ODI of >0.7) and mNGS, which generated a sensitivity of 61.9% and specificity of 82.6%. Further investigation of combination diagnostic performances in different kind of CNS aspergillosis was also conducted. Lowest sensitivity (42.9%) was identified in abscess group, while increased sensitivity (60.0%) was achieved in abscess with encephalitis groups. Combination test exhibited the best performance for encephalitis patients who had only CSF abnormalities, in whom the sensitivity and specificity were 77.8% and 82.6%, respectively. CONCLUSIONS: In conclusion, combination of these two tests might be useful for diagnosis of CNS aspergillosis associated with fungal rhinosinusitis, especially in encephalitis patients.

The association between parental risks and childhood development: findings from a community-based survey in East China.

BACKGROUND: Nurturing care is necessary for optimal early childhood development. This study aimed to investigate the prevalence of parental risks in rural East China and assess their impacts on early development in children younger than three years old. METHODS: This community-based cross-sectional survey was conducted among 3852 caregiver-child pairs in Zhejiang Province from December 2019 to January 2020. Children aged 0 to 3 years were recruited from China's Early Childhood Development Program (ECD). Local child health care providers conducted face-to-face interviews with the primary caregivers. Demographic information of the participants was collected by questionnaire. Each child was screened for parental risk through the Parental Risk Checklist designed by the ECD program. The Ages and Stages Questionnaire (ASQ) was used to identify children with potential developmental delays. Multinomial logistic regression model and linear trend test were applied to assess the association between parental risks and suspected developmental delays. RESULTS: Among the 3852 children included in the analyses, 46.70% had at least one parental risk and 9.01% presented suspected developmental delays in any domain of ASQ. Parental risk was statistically associated with the overall suspected developmental delay in young children (Relative Risk Ratio (RRR): 1.36; 95% confidence interval (CI): 1.08, 1.72; P = 0.010) after adjusting potential confounders. Compared with children with no parental risk, children exposed to 3 or more parental risks had 2.59, 5.76, 3.95, and 2.84 times higher risk of the suspected developmental delay in overall ASQ, communication, problem-solving, and personal-social domain, respectively (P values < 0.05). The linear trend tests found that the more parental risks, the higher possibility of developmental delay (P values < 0.05). CONCLUSIONS: Parental risks are prevalent among children under three years in rural East China, which may increase the risk of developmental delays in children. Meanwhile, parental risk screening can be used to recognize poor nurturing care in primary health care settings. Targeted interventions are warranted to improve nurturing care for optimal early childhood development.

Individualized estimates of intensity-modulated radiotherapy plans after breast conservation surgery for left-sided breast cancer.

OBJECTIVES: The purpose of this study was to explore the influence of individual patient factors, such as volume of the planning target volume (PTV) (VPTV), cardiothoracic ratio (CTR), central lung distance (CLD), and maximal heart distance (MHD), on the design of treatment plans in terms of target dose coverage, integral dose, and dose to organs at risk (OAR) in early breast cancer. METHODS: Ninety-six patients were selected for this study. Radiation doses of 50 Gy and a simultaneous dose of 60 Gy in 25 fractions were administered to the whole breast and tumor bed, respectively. The intensity modulation plan (IMRT) of each patient uses both physical parameters and an equivalent uniform dose (EUD) to optimize the target function. Univariate and multivariate linear regression were used to analyze the relationship between predictive impact factors and OAR percent dose volume, conformity index (CI), and homogeneity index (HI). RESULTS: The average CI and HI values of the left breast cancer plan were 0.595 ± 0.071 (0.3-0.72) and 1.095 ± 0.023 (1.06-1.18), respectively. The CTR (B = 0.21, P = 0.045), VPTV (B = 0.63, P = 0.000), volume of the lung (Vlung) (B = - 0.29, P = 0.005), and MHD (B = 0.22, P = 0.041) were identified as factors influencing the CI index of the left breast cancer intensity modulation plan. VPTV (B = 1.087, P = 0.022) was identified as the influencing factor of the HI index of the left breast cancer intensity modulation plan. volume of the heart (Vheart) (B = - 0.43, P = 0.001) and CLD (B = 0.28, P = 0.008) were influencing factors of the volume of lung (Vlung20) of the lung. The prediction formulas for left-sided breast cancer are noted as follows: CI = 0.459 + 0.19CTR-0.16CLD, Vlung10 = 35.5-0.02Vheart; and Vlung20 = 21.48 + 2.8CLD-0.018Vheart. CONCLUSIONS: CTR, CLD, and MHD can predict the rationality of the parameters of the left breast cancer IMRT. The calculation formula generated based on this information can help the physicist choose the optimal radiation field setting method and improve the quality of the treatment plan.

Unraveling the Antioxidant Activity of 2R,3R-dihydroquercetin.

It has been reported that in an oxidative environment, the flavonoid 2R,3R-dihydroquercetin (2R,3R-DHQ) oxidizes into a product that rearranges to form quercetin. As quercetin is a very potent antioxidant, much better than 2R,3R-DHQ, this would be an intriguing form of targeting the antioxidant quercetin. The aim of the present study is to further elaborate on this targeting. We can confirm the previous observation that 2R,3R-DHQ is oxidized by horseradish peroxidase (HRP), with H2O2 as the oxidant. However, HPLC analysis revealed that no quercetin was formed, but instead an unstable oxidation product. The inclusion of glutathione (GSH) during the oxidation process resulted in the formation of a 2R,3R-DHQ-GSH adduct, as was identified using HPLC with IT-TOF/MS detection. GSH adducts appeared on the B-ring of the 2R,3R-DHQ quinone, indicating that during oxidation, the B-ring is oxidized from a catechol to form a quinone group. Ascorbate could reduce the quinone back to 2R,3R-DHQ. No 2S,3R-DHQ was detected after the reduction by ascorbate, indicating that a possible epimerization of 2R,3R-DHQ quinone to 2S,3R-DHQ quinone does not occur. The fact that no epimerization of the oxidized product of 2R,3R-DHQ is observed, and that GSH adducts the oxidized product of 2R,3R-DHQ on the B-ring, led us to conclude that the redox-modulating activity of 2R,3R-DHQ quinone resides in its B-ring. This could be confirmed by chemical calculation. Apparently, the administration of 2R,3R-DHQ in an oxidative environment does not result in 'biotargeting' quercetin.

Efficient pH-Responsive Nano-Drug Delivery System Based on Dynamic Boronic Acid/Ester Transformation.

Chemotherapy is currently one of the most widely used treatments for cancer. However, traditional chemotherapy drugs normally have poor tumor selectivity, leading to insufficient accumulation at the tumor site and high systemic cytotoxicity. To address this issue, we designed and prepared a boronic acid/ester-based pH-responsive nano-drug delivery system that targets the acidic microenvironment of tumors. We synthesized hydrophobic polyesters with multiple pendent phenylboronic acid groups (PBA-PAL) and hydrophilic PEGs terminated with dopamine (mPEG-DA). These two types of polymers formed amphiphilic structures through phenylboronic ester linkages, which self-assembled to form stable PTX-loaded nanoparticles (PTX/PBA NPs) using the nanoprecipitation method. The resulting PTX/PBA NPs demonstrated excellent drug encapsulation efficiency and pH-triggered drug-release capacity. In vitro and in vivo evaluations of the anticancer activity of PTX/PBA NPs showed that they improved the pharmacokinetics of drugs and exhibited high anticancer activity while with low systemic toxicity. This novel phenylboronic acid/ester-based pH-responsive nano-drug delivery system can enhance the therapeutic effect of anticancer drugs and may have high potential for clinical transformations.

Effects of dietary phosphorus deficiency on the growth performance, hepatic lipid metabolism, and antioxidant capacity of Yellow River Carp Cyprinus carpio haematopterus.

OBJECTIVE: The study aimed to evaluate the effects of phosphorus (P) deficiency in diets on growth performance, hepatic lipid metabolism, and antioxidant capacity in Yellow River Carp Cyprinus carpio haematopterus. METHODS: In this study, 72 healthy experimental fish (initial weight = 12.0 ± 0.1 g [mean ± SE]) were randomly selected and distributed to two groups, with three replicates in each group. The groups were fed either a P-sufficient diet or a P-deficient diet for 8 weeks. RESULT: The P-deficient feed significantly decreased the specific growth rate, feed efficiency, and condition factor of Yellow River Carp. Fish that were fed the P-deficient feed demonstrated higher contents of triglyceride, total cholesterol (T-CHO), and low-density lipoprotein cholesterol in the plasma and a higher T-CHO content in the liver compared to the P-sufficient diet group. In addition, the P-deficient diet significantly reduced the catalase activity level, decreased the glutathione content, and increased the malondialdehyde content in the liver and in the plasma. Furthermore, P deficiency in the diet significantly downregulated the messenger RNA expression of nuclear erythroid 2-related factor 2 and peroxisome proliferator-activated receptor α, whereas it upregulated the messenger RNA expression of tumor necrosis factor α and fatty acid synthase in the liver. CONCLUSION: Dietary P deficiency reduced fish growth performance, induced fat deposition and oxidative stress, and impaired liver health.

[Effect of transurethral thuliumlaser vapoenucleation of the prostate with low-power conventional pulse mode on sexual function in patients with benign prostatic hyperplasia].

OBJECTIVE: To explore the effect of a novel transurethral thulium laser vapoenucleation of the prostate with low-power conventional pulse mode (LP-ThuVEP) on sexual function in patients with benign prostatic hyperplasia (BPH). METHODS: 89 BPH patients admitted to Department of Urology, Jintan People's Hospital, Affiliated to Jiangsu University, from January 2022 to June 2023 were selected and randomly divided into the LP-ThuLEP group (45 cases) and the transurethral plasma kinetic resection of the prostate (TUPKRP) group (44 cases). Perioperative indicators were recorded, and the IPSS, Qmax, Qavg, PVR, and QoL of the two groups of patients before surgery and 3 months and 6 months after surgery were comparatively analyzed. The effect of surgery on male sexual function was evaluated through the International Index of Erectile Function-5 (IIEF-5) score and the Male Sexual Health Questionnaire-Ejaculatory Dysfunction (MSHQ-EjD) score. RESULTS: Compared with the TUPKRP group, the LP-ThuVEP group had no statistically significant difference in operation time (P>0.05), but there were statistical differences in bladder irrigation time and indwelling urinary catheter time (P<0.05) and significant statistical differences in the decrease in hemoglobin on the day of surgery and the disappearance time of gross hematuria induced by defecation after surgery (P<0.001). The perioperative complications of the two groups were comparable. Among the urinary tract symptom indicators, the LP-ThuVEP group had statistically significant differences in IPSS score, QoL score, and PVR compared with the TUPKRP group 3 months after surgery (P<0.05). In terms of male sexual function, there was a statistical difference in IIEF-5 scores between the two groups at 3 months and 6 months after surgery (P<0.05); Except that there was no statistical difference in the ejaculation-related satisfaction scores between the two groups at 3 months after surgery (P>0.05), there had all significant statistical differences in ejaculation function and satisfaction scores between and within the groups at 3 months and 6 months after surgery (P<0.001). CONCLUSION: Compared with TUPKRP, the LP-ThuVEP can also effectively relieve urinary tract obstruction caused by BPH and has the advantages of less damage and faster recovery of erectile function and ejaculatory function of patients.

Evaluation of respiratory samples in etiology diagnosis and microbiome characterization by metagenomic sequencing.

BACKGROUND: The application of clinical mNGS for diagnosing respiratory infections improves etiology diagnosis, however at the same time, it brings new challenges as an unbiased sequencing method informing all identified microbiomes in the specimen. METHODS: Strategy evaluation and metagenomic analysis were performed for the mNGS data generated between March 2017 and October 2019. Diagnostic strengths of four specimen types were assessed to pinpoint the more appropriate type for mNGS diagnosis of respiratory infections. Microbiome complexity was revealed between patient cohorts and infection types. A bioinformatic pipeline resembling diagnosis results was built based upon multiple bioinformatic parameters. RESULTS: The positive predictive values (PPVs) for mNGS diagnosing of non-mycobacterium, Nontuberculous Mycobacteria (NTM), and Aspergillus were obviously higher in bronchoalveolar lavage fluid (BALF) demonstrating the potency of BALF in mNGS diagnosis. Lung tissues and sputum were acceptable for diagnosis of the Mycobacterium tuberculosis (MTB) infections. Interestingly, significant taxonomy differences were identified in sufficient BALF specimens, and unique bacteriome and virome compositions were found in the BALF specimens of tumor patients. Our pipeline showed comparative diagnostic strength with the clinical microbiological diagnosis. CONCLUSIONS: To achieve reliable mNGS diagnosis result, BALF specimens for suspicious common infections, and lung tissues and sputum for doubtful MTB infections are recommended to avoid the false results given by the complexed respiratory microbiomes. Our developed bioinformatic pipeline successful helps mNGS data interpretation and reduces manual corrections for etiology diagnosis.

Addition of Chlorella sorokiniana meal in the diet of juvenile rainbow trout (Oncorhynchus mykiss): Influence on fish growth, gut histology, oxidative stress, immune response, and disease resistance against Aeromonas salmonicida.

This study aimed to assess the effects of dietary addition with Chlorella sorokiniana on fish growth, gut histology, antioxidant capacity, immune response, and disease resistance in rainbow trout. Three diets with similar proximate composition and different Chlorella meal levels were formulated. The control diet, 5% Chlorella diet, and 10% Chlorella diet contained 0%, 5% Chlorella meal, and 10% Chlorella meal, respectively. Each diet was assigned to triplicate tanks containing 30 fish (165.3 ± 0.6 g) in each tank. Fish were fed experimental diets for ninety days. The results showed that the addition of 5% Chlorella in the diet significantly increased feed intake by 19.3% and weight gain rate by 17.3% (P < 0.05) without affecting feed efficiency and gut histology. Diets containing Chlorella meal significantly decreased malonaldehyde contents in the plasma after the lipopolysaccharide (LPS) challenge (P < 0.05). Dietary supplementation with Chlorella meal significantly increased lysozyme (LZM) activity levels (in the head kidney) and immunoglobulin M (IgM) (in the head kidney) and complement component 3 (C3) (in the spleen) contents before the LPS challenge, and simultaneously increased LZM activity levels (in the plasma) and C3 contents (in the plasma and head kidney) after the LPS challenge (P < 0.05). Furthermore, dietary administration of Chlorella meal significantly increased the survival rate of fish infected with Aeromonas salmonicida (P < 0.05). In conclusion, C. sorokiniana can be used to improve fish growth, antioxidant capacity, and immunity.