Influence of temperature on performance and mechanism of advanced synergistic nitrogen removal in lab-scale denitrifying filter with biogenic manganese oxides.

Temperature is a significant operational parameter of denitrifying filter (DF), which affects the microbial activity and the pollutants removal efficiency. This study investigated the influence of temperature on performance of advanced synergistic nitrogen removal (ASNR) of partial-denitrification anammox (PDA) and denitrification, consuming the hydrolytic and oxidation products of refractory organics in the actual secondary effluent (SE) as carbon source. When the test water temperature (TWT) was around 25, 20, 15 and 10 °C, the filtered effluent total nitrogen (TN) was 1.47, 1.70, 2.79 and 5.52 mg/L with the removal rate of 93.38%, 92.25%, 87.33% and 74.87%, and the effluent CODcr was 8.12, 8.45, 10.86 and 12.29 mg/L with the removal rate of 72.41%, 66.17%, 57.35% and 51.87%, respectively. The contribution rate of PDA to TN removal was 60.44%∼66.48%, and 0.77∼0.96 mg chemical oxygen demand (CODcr) was actually consumed to remove 1 mg TN. The identified functional bacteria, such as anammox bacteria, manganese oxidizing bacteria (MnOB), hydrolytic bacteria and denitrifying bacteria, demonstrated that TN was removed by the ASNR, and the variation of the functional bacteria along the DF layer revealed the mechanism of the TWT affecting the efficiency of the ASNR. This technique presented a strong adaptability to the variation of the TWT, therefore, it has broad application prospect and superlative application value in advanced nitrogen removal of municipal wastewater.

DenseNet model incorporating hybrid attention mechanisms and clinical features for pancreatic cystic tumor classification.

PURPOSE: The aim of this study is to develop a deep learning model capable of discriminating between pancreatic plasma cystic neoplasms (SCN) and mucinous cystic neoplasms (MCN) by leveraging patient-specific clinical features and imaging outcomes. The intent is to offer valuable diagnostic support to clinicians in their clinical decision-making processes. METHODS: The construction of the deep learning model involved utilizing a dataset comprising abdominal magnetic resonance T2-weighted images obtained from patients diagnosed with pancreatic cystic tumors at Changhai Hospital. The dataset comprised 207 patients with SCN and 93 patients with MCN, encompassing a total of 1761 images. The foundational architecture employed was DenseNet-161, augmented with a hybrid attention mechanism module. This integration aimed to enhance the network's attentiveness toward channel and spatial features, thereby amplifying its performance. Additionally, clinical features were incorporated prior to the fully connected layer of the network to actively contribute to subsequent decision-making processes, thereby significantly augmenting the model's classification accuracy. The final patient classification outcomes were derived using a joint voting methodology, and the model underwent comprehensive evaluation. RESULTS: Using the five-fold cross validation, the accuracy of the classification model in this paper was 92.44%, with an AUC value of 0.971, a precision rate of 0.956, a recall rate of 0.919, a specificity of 0.933, and an F1-score of 0.936. CONCLUSION: This study demonstrates that the DenseNet model, which incorporates hybrid attention mechanisms and clinical features, is effective for distinguishing between SCN and MCN, and has potential application for the diagnosis of pancreatic cystic tumors in clinical practice.

Thermoregulatory pathway underlying the pyrogenic effects of prostaglandin E2 in the lateral parabrachial nucleus of male rats.

It has been shown that prostaglandin (PG) E2 synthesized in the lateral parabrachial nucleus (LPBN) is involved in lipopolysaccharide-induced fever. But the neural mechanisms of how intra-LPBN PGE2 induces fever remain unclear. In this study, we investigated whether the LPBN-preoptic area (POA) pathway, the thermoafferent pathway for feed-forward thermoregulatory responses, mediates fever induced by intra-LPBN PGE2 in male rats. The core temperature (Tcore) was monitored using a temperature radiotelemetry transponder implanted in rat abdomen. We showed that microinjection of PGE2 (0.28 nmol) into the LPBN significantly enhanced the density of c-Fos-positive neurons in the median preoptic area (MnPO). The chemical lesioning of MnPO with ibotenate or selective genetic lesioning or inhibition of the LPBN-MnPO pathway significantly attenuated fever induced by intra-LPBN injection of PGE2. We demonstrated that EP3 receptor was a pivotal receptor for PGE2-induced fever, since microinjection of EP3 receptor agonist sulprostone (0.2 nmol) or EP3 receptor antagonist L-798106 (2 nmol) into the LPBN mimicked or weakened the pyrogenic action of LPBN PGE2, respectively, but this was not the case for EP4 and EP1 receptors. Whole-cell recording from acute LPBN slices revealed that the majority of MnPO-projecting neurons originating from the external lateral (el) and dorsal (d) LPBN were excited and inhibited, respectively, by PGE2 perfusion, initiating heat-gain and heat-loss mechanisms. The amplitude but not the frequency of spontaneous and miniature glutamatergic excitatory postsynaptic currents (sEPSCs and mEPSCs) in MnPO-projecting LPBel neurons increased after perfusion with PGE2; whereas the frequency and amplitude of spontaneous inhibitory postsynaptic currents (sIPSCs) and the A-type potassium (IA) current density did not change. In MnPO-projecting LPBd neurons, neither sEPSCs nor sIPSCs responded to PGE2; however, the IA current density was significantly increased by PGE2 perfusion. These electrophysiological responses and the thermoeffector reactions to intra-LPBN PGE2 injection, including increased brown adipose tissue thermogenesis, shivering, and decreased heat dissipation, were all abolished by L-798106, and mimicked by sulprostone. These results suggest that the pyrogenic effects of intra-LPBN PGE2 are mediated by both the inhibition of the LPBd-POA pathway through the EP3 receptor-mediated activation of IA currents and the activation of the LPBel-POA pathway through the selective enhancement of glutamatergic synaptic transmission via EP3 receptors.

Astragaloside-IV promotes autophagy via the Akt/mTOR pathway to improve cellular lipid deposition.

The current study aimed to investigate the potential role of astragaloside IV (AS-IV) in improving cellular lipid deposition and its underlying mechanism. A fatty liver cell model was established by treating hepatoma cells with palmitic acid. AS-IV and SC79 were used for treatment. Oil Red O staining was applied to detect intracellular lipid deposition, and transmission electron microscopy was utilized to assess autophagosome formation. Immunofluorescence double staining was applied to determine microtubule-associated proteins 1A/1B light chain 3 (LC3) expression. Western blot analysis was performed to detect the expression of LC3, prostacyclin, Beclin-1, V-akt murine thymoma viral oncogene homolog (Akt), phosphorylated Akt, mTOR, and phosphorylated mTOR. Oil Red O staining revealed that AS-IV reduced intracellular lipid accumulation. Further, it increased autophagosome synthesis and the expression of autophagy proteins LC3 and Beclin-1 in the cells. It also reduced the phosphorylation levels of Akt and mTOR and the levels of prostacyclin. However, the effects of AS-IV decreased with SC79 treatment. In addition, LC3B + BODIPY493/503 fluorescence double staining showed that AS-IV reduced intracellular lipid deposition levels by enhancing autophagy. AS-IV can reduce lipid aggregation in fatty liver cells, which can be related to enhanced hepatocyte autophagy by inhibiting the Akt/mTOR signaling pathway.

Pre-operative enhanced magnetic resonance imaging combined with clinical features predict early recurrence of hepatocellular carcinoma after radical resection.

BACKGROUND: Indentifying predictive factors for postoperative recurrence of hepatocellular carcinoma (HCC) has great significance for patient prognosis. AIM: To explore the value of gadolinium ethoxybenzyl diethylenetriamine pentaacetic acid (Gd-EOB-DTPA) enhanced magnetic resonance imaging (MRI) combined with clinical features in predicting early recurrence of HCC after resection. METHODS: A total of 161 patients with pathologically confirmed HCC were enrolled. The patients were divided into early recurrence and non-early recurrence group based on the follow-up results. The clinical, laboratory, pathological results and Gd-EOB-DTPA enhanced MRI imaging features were analyzed. RESULTS: Of 161 patients, 73 had early recurrence and 88 were had non-early recurrence. Univariate analysis showed that patient age, gender, serum alpha-fetoprotein level, the Barcelona Clinic Liver Cancer stage, China liver cancer (CNLC) stage, microvascular invasion (MVI), pathological satellite focus, tumor size, tumor number, tumor boundary, tumor capsule, intratumoral necrosis, portal vein tumor thrombus, large vessel invasion, nonperipheral washout, peritumoral enhancement, hepatobiliary phase (HBP)/tumor signal intensity (SI)/peritumoral SI, HBP peritumoral low signal and peritumoral delay enhancement were significantly associated with early recurrence of HCC after operation. Multivariate logistic regression analysis showed that patient age, MVI, CNLC stage, tumor boundary and large vessel invasion were independent predictive factors. External data validation indicated that the area under the curve of the combined predictors was 0.861, suggesting that multivariate logistic regression was a reasonable predictive model for early recurrence of HCC. CONCLUSION: Gd-EOB-DTPA enhanced MRI combined with clinical features would help predicting the early recurrence of HCC after operation.

Tumour organoids and assembloids: Patient-derived cancer avatars for immunotherapy.

BACKGROUND: Organoid technology is an emerging and rapidly growing field that shows promise in studying organ development and screening therapeutic regimens. Although organoids have been proposed for a decade, concerns exist, including batch-to-batch variations, lack of the native microenvironment and clinical applicability. MAIN BODY: The concept of organoids has derived patient-derived tumour organoids (PDTOs) for personalized drug screening and new drug discovery, mitigating the risks of medication misuse. The greater the similarity between the PDTOs and the primary tumours, the more influential the model will be. Recently, 'tumour assembloids' inspired by cell-coculture technology have attracted attention to complement the current PDTO technology. High-quality PDTOs must reassemble critical components, including multiple cell types, tumour matrix, paracrine factors, angiogenesis and microorganisms. This review begins with a brief overview of the history of organoids and PDTOs, followed by the current approaches for generating PDTOs and tumour assembloids. Personalized drug screening has been practised; however, it remains unclear whether PDTOs can predict immunotherapies, including immune drugs (e.g. immune checkpoint inhibitors) and immune cells (e.g. tumour-infiltrating lymphocyte, T cell receptor-engineered T cell and chimeric antigen receptor-T cell). PDTOs, as cancer avatars of the patients, can be expanded and stored to form a biobank. CONCLUSION: Fundamental research and clinical trials are ongoing, and the intention is to use these models to replace animals. Pre-clinical immunotherapy screening using PDTOs will be beneficial to cancer patients. KEY POINTS: The current PDTO models have not yet constructed key cellular and non-cellular components. PDTOs should be expandable and editable. PDTOs are promising preclinical models for immunotherapy unless mature PDTOs can be established. PDTO biobanks with consensual standards are urgently needed.

Insecticidal activity of Ageratina adenophora (Asteraceae) extract against Limax maximus (Mollusca, Limacidae) at different developmental stages and its chemical constituent analysis.

Limax maximus, or great gray slug, is a common agriculture pest. The pest infests crops during their growth phase, creating holes in vegetable leaves, particularly in seedlings and tender leaves. A study was conducted to assess the insecticidal activity of Ageratina adenophora extract against these slugs. Factors such as fecundity, growth, hatching rate, offspring survival rate, protective enzyme activity, and detoxifying enzyme activity were examined in slugs exposed to the extract's sublethal concentration (LC50) for two different durations (24 and 48 h). The phytochemical variability of the extracts was also studied. The LC50 value of the A. adenophora extract against L. maximus was 35.9 mg/mL. This extract significantly reduced the hatching rate of eggs and the survival rate of offspring hatched from exposed eggs compared with the control. The lowest rates were observed in those exposed for 48 h. The survival, growth, protective enzyme, and detoxification activity of newly hatched and 40-day-old slugs decreased. The A. adenophora extract contained tannins, flavonoids, and saponins, possibly contributing to their biological effects. These results suggest that the extract could be used as an alternative treatment for slug extermination, effectively controlling this species.

TSPO deficiency exacerbates acute lung injury via NLRP3 inflammasome-mediated pyroptosis.

BACKGROUND: Acute respiratory distress syndrome (ARDS) is a common cause of respiratory failure in many critically disease patients. Although inflammasome activation plays an important role in the induction of acute lung injury (ALI) and ARDS, the regulatory mechanism of this process is still unclear. When cells are stimulated by inflammation, the integrity and physiological function of mitochondria play a crucial part in pyroptosis. However, the underlying mechanisms and function of mitochondrial proteins in the process of pyroptosis are largely not yet known. Here, we identified the 18-kDa translocator protein (TSPO), a mitochondrial outer membrane protein, as an important mediator regulating nucleotide-binding domain, leucine-rich repeat, and pyrin domain-containing protein 3 (NLRP3) inflammasome activation in macrophages during ALI. METHODS: TSPO gene knockout (KO) and lipopolysaccharide (LPS)-induced ALI/ARDS mouse models were employed to investigate the biological role of TSPO in the pathogenesis of ARDS. Murine macrophages were used to further characterize the effect of TSPO on the NLRP3 inflammasome pathway. Activation of NLRP3 inflammasome through LPS + adenosine triphosphate (ATP) co-stimulation, followed by detection of mitochondrial membrane potential, reactive oxygen species (ROS) production, and cell death was preformed to evaluate the potential biological function of TSPO. Comparisons between two groups were performed with a two-sided unpaired t-test. RESULTS: TSPO-KO mice exhibited more severe pulmonary inflammation in response to LPS-induced ALI. TSPO deficiency resulted in enhanced activation of the NLRP3 inflammasome pathway, promoting more proinflammatory cytokine production of macrophages in LPS-injured lung tissue, including interleukin (IL)-1ß, IL-18, and macrophage inflammatory protein (MIP)-2. Mitochondria in TSPO-KO macrophages tended to depolarize in response to cellular stress. The increased production of mitochondrial damage-associated molecular pattern (mtDAMP) led to enhanced mitochondrial membrane depolarization and pyroptosis in TSPO-KO cells. CONCLUSION: TSPO may be the key regulatory of cellular pyroptosis, it plays a vital protective role in ARDS occurrence and development.

A novel associative memory model based on semi-tensor product (STP).

A good intelligent learning model is the key to complete recognition of scene information and accurate recognition of specific targets in intelligent unmanned system. This study proposes a new associative memory model based on the semi-tensor product (STP) of matrices, to address the problems of information storage capacity and association. First, some preliminaries are introduced to facilitate modeling, and the problem of information storage capacity in the application of discrete Hopfield neural network (DHNN) to associative memory is pointed out. Second, learning modes are equivalently converted into their algebraic forms by using STP. A memory matrix is constructed to accurately remember these learning modes. Furthermore, an algorithm for updating the memory matrix is developed to improve the association ability of the model. And another algorithm is provided to show how our model learns and associates. Finally, some examples are given to demonstrate the effectiveness and advantages of our results. Compared with mainstream DHNNs, our model can remember learning modes more accurately with fewer nodes.

Efficacy of borneol-gypsum in skin regeneration and pain control in toxic epidermal necrolysis: A case report.

BACKGROUND: Toxic epidermal necrolysis (TEN) is a life-threatening dermatological emergency mainly induced by drug hypersensitivity reactions. Standard management includes discontinuation of culprit drug and application of immunomodulatory therapy. However, mortality remains high due to complications like septic shock and multiorgan failures. Innovative approaches for skin care are crucial. This report introduces borneol-gypsum, a traditional Chinese drug but a novel dressing serving as an adjuvant of TEN therapy, might significantly improve skin conditions and patient outcomes in TEN. CASE SUMMARY: A 38-year-old woman diagnosed with eosinophilic granulomatosis with polyangiitis experienced gangrenous complications and motor nerve involvement. After initial treatment of high-dose corticosteroids and cyclophosphamide, symptom of foot drop improved, absolute eosinophil counts decreased, while limb pain sustained. Duloxetine was added to alleviate her symptom. Subsequently, TEN developed. Additional topical application of borneol-gypsum dressing not only protected the skin lesions from infection but also significantly eased localized pain. This approach demonstrated its merit in TEN management by promoting skin healing and potentially reducing infection risks. CONCLUSION: Borneol-gypsum dressing is a promising adjuvant that could significantly improve TEN management, skin regeneration, and patient comfort.

Demonstrating Bioequivalence for Two Dose Strengths of Niraparib and Abiraterone Acetate Dual-Action Tablets Versus Single Agents: Utility of Clinical Study Data Supplemented with Modeling and Simulation.

BACKGROUND AND OBJECTIVE: The combination of niraparib and abiraterone acetate (AA) plus prednisone is under investigation for the treatment of patients with metastatic castration-resistant prostate cancer (mCRPC) and metastatic castration-sensitive prostate cancer (mCSPC). Regular-strength (RS) and lower-strength (LS) dual-action tablets (DATs), comprising niraparib 100 mg/AA 500 mg and niraparib 50 mg/AA 500 mg, respectively, were developed to reduce pill burden and improve patient experience. A bioequivalence (BE)/bioavailability (BA) study was conducted under modified fasting conditions in patients with mCRPC to support approval of the DATs. METHODS: This open-label randomized BA/BE study (NCT04577833) was conducted at 14 sites in the USA and Europe. The study had a sequential design, including a 21-day screening phase, a pharmacokinetic (PK) assessment phase comprising three periods [namely (1) single-dose with up to 1-week run-in, (2) daily dose on days 1-11, and (3) daily dose on days 12-22], an extension where both niraparib and AA as single-agent combination (SAC; reference) or AA alone was continued from day 23 until discontinuation, and a 30-day follow-up phase. Patients were randomly assigned in a parallel-group design (four-sequence randomization) to receive a single oral dose of niraparib 100 mg/AA 1000 mg as a LS-DAT or SAC in period 1, and patients continued as randomized into a two-way crossover design during periods 2 and 3 where they received niraparib 200 mg/AA 1000 mg once daily as a RS-DAT or SAC. The design was powered on the basis of crossover assessment of RS-DAT versus SAC. During repeated dosing (periods 2 and 3, and extension phase), all patients also received prednisone/prednisolone 5 mg twice daily. Plasma samples were collected for measurement of niraparib and abiraterone plasma concentrations. Statistical assessment of the RS-DAT and LS-DAT versus SAC was performed on log-transformed pharmacokinetic parameters data from periods 2 and 3 (crossover) and from period 1 (parallel), respectively. Additional paired analyses and model-based bioequivalence assessments were conducted to evaluate the similarity between the LS-DAT and SAC. RESULTS: For the RS-DAT versus SAC, the 90% confidence intervals (CI) of geometric mean ratios (GMR) for maximum concentration at a steady state (Cmax,ss) and area under the plasma concentration-time curve from 0-24 h at a steady state (AUC 0-24h,ss) were respectively 99.18-106.12% and 97.91-104.31% for niraparib and 87.59-106.69 and 86.91-100.23% for abiraterone. For the LS-DAT vs SAC, the 90% CI of GMR for AUC0-72h of niraparib was 80.31-101.12% in primary analysis, the 90% CI of GMR for Cmax,ss and AUC 0-24h,ss of abiraterone was 85.41-118.34% and 86.51-121.64% respectively, and 96.4% of simulated LS-DAT versus SAC BE trials met the BE criteria for both niraparib and abiraterone. CONCLUSIONS: The RS-DAT met BE criteria (range 80%-125%) versus SAC based on 90% CI of GMR for Cmax,ss and AUC 0-24h,ss. The LS-DAT was considered BE to SAC on the basis of the niraparib component meeting the BE criteria in the primary analysis for AUC 0-72h; abiraterone meeting the BE criteria in additional paired analyses based on Cmax,ss and AUC 0-24h,ss; and the percentage of simulated LS-DAT versus SAC BE trials meeting the BE criteria for both. GOV IDENTIFIER: NCT04577833.

Effects of Desmodium caudatum on Gastrointestinal Hormones and Intestinal Flora in Rats with Gastritis.

In order to preliminarily explore the effects of Desmodium caudatum on gastritis and intestinal flora in rats, a chronic gastritis rat model was established using the classic sodium salicylate method. Eighteen SPF rats were divided into three groups: the control group (Group C), the model group (Group M), and the treatment group (Group T). Pathological sections of the gastric wall were taken from rats in each group. Furthermore, the concentrations of gastrin and malondialdehyde in the serum of rats in each group were determined by ELISA. Additionally, the effects of D. caudatum on the intestinal flora of rats with gastritis were explored through a detailed comparison of gut bacterial communities in the three groups, employing Illumina-based 16S rRNA gene sequencing. The results indicated that D. caudatum decoction could reduce the malondialdehyde content and increase the gastrin content. Moreover, D. caudatum decoction was found to enhance the diversity and abundance of intestinal flora, exerting a positive impact on the treatment of gastritis by regulating and restoring the intestinal flora.

Tuning the Flat Band in Bi2O2Se by Pressure to Induce Superconductivity.

The discovery of superconductivity in twisted bilayer graphene has reignited enthusiasm in the field of flat-band superconductivity. However, important challenges remain, such as constructing a flat-band structure and inducing a superconducting state in materials. Here, we successfully achieved superconductivity in Bi2O2Se by pressure-tuning the flat-band electronic structure. Experimental measurements combined with theoretical calculations reveal that the occurrence of pressure-induced superconductivity at 30 GPa is associated with a flat-band electronic structure near the Fermi level. Moreover, in Bi2O2Se, a van Hove singularity is observed at the Fermi level alongside pronounced Fermi surface nesting. These remarkable features play a crucial role in promoting strong electron-phonon interactions, thus potentially enhancing the superconducting properties of the material. These findings demonstrate that pressure offers a potential experimental strategy for precisely tuning the flat band and achieving superconductivity.

Polyaspartic acid increases potassium content and reduces the ratio of total sugar to nicotine in tobacco leaves.

Tobacco is an important cash crop in China, but the low potassium (K) content and high ratio of total sugar to nicotine in tobacco leaves have seriously affected the quality of tobacco leaves. As a fertilizer synergist, polyaspartic acid (PASP) can improve the K content in tobacco leaves, but it is unknown how it affects the K content in different parts of tobacco leaves, and how PASP affects the ratio of total sugar to nicotine in tobacco leaves has not been reported. Therefore, "Zhongyan 100" was selected for pot experiments with 5 different PASP addition levels: CK (0.0 %), P1 (0.1 %), P2 (0.2 %), P3 (0.4 %) and P4 (0.6 %), to reveal the effects of PASP on tobacco growth, K content, sugar content, nicotine content and the ratio of total sugar to nicotine in different tobacco parts, and determine the optimal PASP dosage for regulating the K content and the ratio of total sugar to nicotine in tobacco. The results showed that P1 (0.1 %) and P2 (0.2 %) only had slighter effects on tobacco growth and quality, while P3 (0.4 %) and P4 (0.6 %)treatments significantly promoted dry matter accumulation, increased K and nicotine content in leaves, decreased reducing sugar and total soluble sugar content in leaves, thereby reducing the ratio of total sugar to nicotine in tobacco leaves, especially in upper leaves. Considering the economic cost savings, 0.4% PASP was determined as the best application level to improve the growth and quality of tobacco. Thus, proper application of PASP is beneficial to improve tobacco leaf quality and reduce chemical K fertilizer application, thereby decreasing agricultural environmental risks of chemical fertilizer and alleviating the rapid depletion of potash in the world.

An optimized short-term steroid therapy for chronic drug-induced liver injury: A prospective randomized clinical trial.

BACKGROUND AND AIMS: The use of corticosteroids in chronic drug-induced liver injury (DILI) is an important issue. Our previous randomized controlled trial showed that patients with chronic DILI benefited from a 48-week steroid stepwise reduction (SSR) regimen. However, it remains unclear whether a shorter course of therapy can achieve similar efficacy. In this study, we aimed to assess whether a 36-week SSR can achieve efficacy similar to that of 48-week SSR. METHODS: A randomized open-label trial was performed. Eligible patients were randomly assigned to the 36- or 48-week (1:1) SSR group. Liver biopsies were performed at baseline and at the end of treatment. The primary outcome was the proportion of patients with relapse rate (RR). The secondary outcomes were improvement in liver histology and safety. RESULTS: Of the 90 participants enrolled, 84 (87.5%) completed the trial, and 62 patients (68.9%) were women. Hepatocellular damage was observed in 53.4% of the cohort. The RR was 7.1% in the 36-week SSR group but 4.8% in the 48-week SSR group, as determined by per-protocol set analysis (p = 1.000). Significant histological improvements in histological activity (93.1% vs. 92.9%, p = 1.000) and fibrosis (41.4% vs. 46.4%, p = .701) were observed in both the groups. Biochemical normalization time did not differ between the two groups. No severe adverse events were observed. CONCLUSIONS: Both the 36- and 48-week SSR regimens demonstrated similar biochemical response and histological improvements with good safety, supporting 36-week SSR as a preferable therapeutic choice (ClinicalTrials.gov, NCT03266146).

Bioaugmented ensiling of sweet sorghum with Pichia anomala and cellulase and improved enzymatic hydrolysis of silage via ball milling.

Sweet sorghum, as a seasonal energy crop, is rich in cellulose and hemicellulose that can be converted into biofuels. This work aims at investigating the effects of synergistic regulation of Pichia anomala and cellulase on ensiling quality and microbial community of sweet sorghum silages as a storage and pretreatment method. Furthermore, the combined pretreatment effects of ensiling and ball milling on sweet sorghum were evaluated by microstructure change and enzymatic hydrolysis. Based on membership function analysis, the combination of P. anomala and cellulase (PA + CE) significantly improved the silage quality by preserving organic components and promoting fermentation characteristics. The bioaugmented ensiling with PA + CE restructured the bacterial community by facilitating Lactobacillus and inhibiting undesired microorganisms by killer activity of P. anomala. The combined bioaugmented ensiling pretreatment with ball milling significantly increased the enzymatic hydrolysis efficiency (EHE) to 71%, accompanied by the increased specific surface area and decreased pore size/crystallinity of sweet sorghum. Moreover, the EHE after combined pretreatment was increased by 1.37 times compared with raw material. Hence, the combined pretreatment was demonstrated as a novel strategy to effectively enhance enzymatic hydrolysis of sweet sorghum.

Effectiveness and safety of Moluodan in the treatment of precancerous lesions of gastric cancer: A randomized clinical trial.

OBJECTIVE: To investigate the clinical potential and safety of Moluodan to reverse gastric precancerous lesions. METHODS: Patients aged 18-70 years diagnosed with moderate-to-severe atrophy and/or moderate-to-severe intestinal metaplasia, with or without low-grade dysplasia, and negative for Helicobacter pylori were recruited in this randomized, double-blind, parallel-controlled trial. The primary outcome was the improvement of global histological diagnosis at 1-year follow-up endoscopy using the operative link for gastritis assessment, the operative link for gastric intestinal metaplasia assessment, and the disappearance rate of dysplasia. RESULTS: Between November 3, 2017 and January 27, 2021, 166 subjects were randomly assigned to the Moluodan group, 168 to the folic acid group, 84 to the combination group, and 84 to the high-dose Moluodan group. The improvement in global histological diagnosis was achieved in 60 (39.5%) subjects receiving Moluodan, 59 (37.8%) receiving folic acid, 26 (32.1%) receiving the combined drugs, and 36 (47.4%) receiving high-dose Moluodan. Moluodan was non-inferior to folic acid (95% confidence interval: -9.2 to 12.5; P = 0.02). High-dose Moluodan had a trend for better protective efficacy, though there was no statistical significance. The disappearance rate of dysplasia was 82.8% in the Moluodan group, which was superior to folic acid (53.9%; P = 0.006). No drug-related serious adverse events were observed. CONCLUSIONS: One pack of Moluodan three times daily for 1 year was safe and effective in reversing gastric precancerous lesions, especially dysplasia. Doubling its dose showed a better efficacy trend.

BZW2 promotes malignant progression in lung adenocarcinoma through enhancing the ubiquitination and degradation of GSK3ß.

The role of Basic leucine zipper and W2 domains 2 (BZW2) in the advancement of different types of tumors is noteworthy, but its involvement and molecular mechanisms in lung adenocarcinoma (LUAD) remain uncertain. Through this investigation, it was found that the upregulation of BZW2 was observed in LUAD tissues, which was associated with an unfavorable prognosis for individuals diagnosed with LUAD, as indicated by data from Gene Expression Omnibus and The Cancer Genome Atlas databases. Based on the clinicopathologic characteristics of LUAD patients from the tissue microarray, both univariate and multivariate analyses indicated that BZW2 functioned as an independent prognostic factor for LUAD. In terms of mechanism, BZW2 interacted with glycogen synthase kinase-3 beta (GSK3ß) and enhanced the ubiquitination-mediated degradation of GSK3ß through slowing down of the dissociation of the ubiquitin ligase complex, which consists of GSK3ß and TNF receptor-associated factor 6. Moreover, BZW2 stimulated Wnt/ß-catenin signaling pathway through GSK3ß, thereby facilitating the advancement of LUAD. In conclusion, BZW2 was a significant promoter of LUAD. The research we conducted identified a promising diagnostic and therapeutic target for LUAD.

Rationale and Trial Protocol for a Double-Blinded Randomized Controlled Trial to assess the Impact of a Concomitant Crural Repair during Laparoscopic Sleeve Gastrectomy in Patients with a Lax Gastroesophageal Junction without Frank Hiatal Hernia (REPAIR trial protocol).

INTRODUCTION: Laparoscopic sleeve gastrectomy (LSG) is associated with postoperative gastroesophageal reflux disease (GERD) and erosive esophagitis (EE). The role of crural repair during LSG is still controversial. The preoperative laxity of the gastroesophageal junction (GEJ), graded by the Hill's classification, is more predictive for postoperative GERD and EE after LSG than the presence of a hiatal hernia seen on endoscopy. Thus, the authors hypothesize that a concomitant crural repair in a specific subgroup of patients with a lax GEJ (Hill's III) may reduce the incidence of postoperative GERD and EE. METHODS: A double-blinded, randomized controlled trial of patients with Hill's III GEJ undergoing LSG will be randomized to a concomitant crural repair (experimental) versus LSG alone (control). Primary outcome measures will be presence of EE at 1-year. Secondary outcome measures will include proton pump inhibitor use, postoperative complications, operative time, blood loss, quality of life, GERD and gastrointestinal symptoms. CONCLUSION: Conflicting crural repair results may be explained by differences in preoperative GEJ laxity. Patients with a frank hiatal hernia and patulous GEJ (Hill's IV) have a very high, while patients with an apposed GEJ (Hill's I, Hill's II) have a low incidence of postoperative GERD and EE respectively. Thus, the authors hypothesize that patients with a lax GEJ without frank hiatal hernia (Hill's III), might benefit from a crural repair. This study results can potentially highlight the clinical importance of preoperative endoscopic evaluation of the GEJ in all patients planned for LSG, to determine which subgroup patients may benefit from a crural repair. (Clinicaltrials.gov: NCT05330910, Registered 15-April-2022).

Construction and validation of a predictive model of invasive adenocarcinoma in pure ground-glass nodules less than 2 cm in diameter.

OBJECTIVES: In this study, we aimed to develop a multiparameter prediction model to improve the diagnostic accuracy of invasive adenocarcinoma in pulmonary pure glass nodules. METHOD: We included patients with pulmonary pure glass nodules who underwent lung resection and had a clear pathology between January 2020 and January 2022 at the Qilu Hospital of Shandong University. We collected data on the clinical characteristics of the patients as well as their preoperative biomarker results and computed tomography features. Thereafter, we performed univariate and multivariate logistic regression analyses to identify independent risk factors, which were then used to develop a prediction model and nomogram. We then evaluated the recognition ability of the model via receiver operating characteristic (ROC) curve analysis and assessed its calibration ability using the Hosmer-Lemeshow test and calibration curves. Further, to assess the clinical utility of the nomogram, we performed decision curve analysis. RESULT: We included 563 patients, comprising 174 and 389 cases of invasive and non-invasive adenocarcinoma, respectively, and identified seven independent risk factors, namely, maximum tumor diameter, age, serum amyloid level, pleural effusion sign, bronchial sign, tumor location, and lobulation. The area under the ROC curve was 0.839 (95% CI: 0.798-0.879) for the training cohort and 0.782 (95% CI: 0.706-0.858) for the validation cohort, indicating a relatively high predictive accuracy for the nomogram. Calibration curves for the prediction model also showed good calibration for both cohorts, and decision curve analysis showed that the clinical prediction model has clinical utility. CONCLUSION: The novel nomogram thus constructed for identifying invasive adenocarcinoma in patients with isolated pulmonary pure glass nodules exhibited excellent discriminatory power, calibration capacity, and clinical utility.