Heterodimensional superlattice with in-plane anomalous Hall effect.

Superlattices-a periodic stacking of two-dimensional layers of two or more materials-provide a versatile scheme for engineering materials with tailored properties1,2. Here we report an intrinsic heterodimensional superlattice consisting of alternating layers of two-dimensional vanadium disulfide (VS2) and a one-dimensional vanadium sulfide (VS) chain array, deposited directly by chemical vapour deposition. This unique superlattice features an unconventional 1T stacking with a monoclinic unit cell of VS2/VS layers identified by scanning transmission electron microscopy. An unexpected Hall effect, persisting up to 380 kelvin, is observed when the magnetic field is in-plane, a condition under which the Hall effect usually vanishes. The observation of this effect is supported by theoretical calculations, and can be attributed to an unconventional anomalous Hall effect owing to an out-of-plane Berry curvature induced by an in-plane magnetic field, which is related to the one-dimensional VS chain. Our work expands the conventional understanding of superlattices and will stimulate the synthesis of more extraordinary superstructures.

Sustainable Copolymer Synthesis from Carbon Dioxide and Butadiene.

Carbon dioxide (CO2) has long been recognized as an ideal C1 feedstock comonomer for producing sustainable materials because it is renewable, abundant, and cost-effective. However, activating CO2 presents a significant challenge because it is highly oxidized and stable. A CO2/butadiene-derived δ-valerolactone (EVP), generated via palladium-catalyzed telomerization between CO2 and butadiene, has emerged as an attractive intermediate for producing sustainable copolymers from CO2 and butadiene. Owing to the presence of two active carbon-carbon double bonds and a lactone unit, EVP serves as a versatile intermediate for creating sustainable copolymers with a CO2 content of up to 29 wt % (33 mol %). In this Review, advances in the synthesis of copolymers from CO2 and butadiene with divergent structures through various polymerization protocols have been summarized. Achievements made in homo- and copolymerization of EVP or its derivatives are comprehensively reviewed, while the postmodification of the obtained copolymers to access new polymers are also discussed. Meanwhile, potential applications of the obtained copolymers are also discussed. The literature references were sorted into sections based on polymerization strategies and mechanisms, facilitating readers in gaining a comprehensive view of the present chemistry landscape and inspiring innovative approaches to synthesizing novel CO2-derived copolymers.

Clinical trajectories preceding incident dementia up to 15 years before diagnosis: a large prospective cohort study.

BACKGROUND: Dementia has a long prodromal stage with various pathophysiological manifestations; however, the progression of pre-diagnostic changes remains unclear. We aimed to determine the evolutional trajectories of multiple-domain clinical assessments and health conditions up to 15 years before the diagnosis of dementia. METHODS: Data was extracted from the UK-Biobank, a longitudinal cohort that recruited over 500,000 participants from March 2006 to October 2010. Each demented subject was matched with 10 healthy controls. We performed logistic regressions on 400 predictors covering a comprehensive range of clinical assessments or health conditions. Their evolutional trajectories were quantified using adjusted odds ratios (ORs) and FDR-corrected p-values under consecutive timeframes preceding the diagnosis of dementia. FINDINGS: During a median follow-up of 13.7 [Interquartile range, IQR 12.9-14.2] years until July 2022, 7620 subjects were diagnosed with dementia. In general, upon approaching the diagnosis, demented subjects witnessed worse functional assessments and a higher prevalence of health conditions. Associations up to 15 years preceding the diagnosis comprised declined physical strength (hand grip strength, OR 0.65 [0.63-0.67]), lung dysfunction (peak expiratory flow, OR 0.78 [0.76-0.81]) and kidney dysfunction (cystatin C, OR 1.13 [1.11-1.16]), comorbidities of coronary heart disease (OR 1.78 [1.67-1.91]), stroke (OR 2.34 [2.1-1.37]), diabetes (OR 2.03 [1.89-2.18]) and a series of mental disorders. Cognitive functions in multiple tests also demonstrate decline over a decade before the diagnosis. Inadequate activity (3-5 year, overall time of activity, OR 0.82 [0.73-0.92]), drowsiness (3-5 year, sleep duration, OR 1.13 [1.04-1.24]) and weight loss (0-5 year, weight, OR 0.9 [0.83-0.98]) only exhibited associations within five years before the diagnosis. In addition, serum biomarkers of enriched endocrine, dysregulations of ketones, deficiency of brand-chain amino acids and polyunsaturated fatty acids were found in a similar prodromal time window and can be witnessed as the last pre-symptomatic conditions before the diagnosis. INTERPRETATION: Our findings present a comprehensive temporal-diagnostic landscape preceding incident dementia, which could improve selection for preventive and early disease-modifying treatment trials.

What Metals Should Be Used to Mediate Electrosynthesis of Ammonia from Nitrogen and Hydrogen from a Thermodynamic Standpoint?

Recently, metal-mediated electrochemical conversion of nitrogen and hydrogen to ammonia (M-eNRRs) has been attracting intense research attention as a potential route for ammonia synthesis under ambient conditions. However, which metals should be used to mediate M-eNRRs remains unanswered. This work provides an extensive comparison of the energy consumption in the classical Haber Bosch (H-B) process and the M-eNRRs. The results indicate that when employing lithium and calcium, metals popularly used to mediate the M-eNRRs, the energy consumption is more than 10 times greater than that of the H-B process even assuming a 100% Faradaic efficiency and zero overpotentials. Only electrosynthesis with a cell voltage not exceeding 0.38 V might have the potential to rival the H-B process from an energetic perspective. A further analysis of other metals in the periodic table reveals that only some heavy metals, including In, Tl, Co, Ni, Ga, Mo, Sn, Pb, Fe, W, Ge, Re, Bi, Cu, Po, Tc, Ru, Rh, Ag, Hg, Pd, Ir, Pt, and Au, can potentially consume less energy than that of the H-B process purely from a thermodynamic standpoint, but whether they can activate N2 under ambient conditions is yet to be explored. This work shows the importance of performing thermodynamic analysis for the development of an innovative strategy to synthesize ammonia with the ultimate goal of replacing the H-B process on a large scale.

A Novel Classification System of Renal Hilar Tumors for Surgical Guidance: Technique, Outcome, and Safety.

BACKGROUND: This study was designed to develop an innovative classification and guidance system for renal hilar tumors and to assess the safety and effectiveness of robot-assisted partial nephrectomy (RAPN) for managing such tumors. METHODS: A total of 179 patients undergoing RAPN for renal hilar tumors were retrospectively reviewed. A novel classification system with surgical techniques was introduced and the perioperative features, tumor characteristics, and the efficacy and safety of RAPN were compared within subgroups. RESULTS: We classified the tumors according to our novel system as follows: 131 Type I, 35 Type II, and 13 Type III. However, Type III had higher median R.E.N.A.L., PADUA, and ROADS scores compared with the others (all p < 0.001), indicating increased operative complexity and higher estimated blood loss [180.00 (115.00-215.00) ml]. Operative outcomes revealed significant disparities between Type III and the others, with longer operative times [165.00 (145.00-200.50) min], warm ischemia times [24.00 (21.50-30.50) min], tumor resection times [13.00 (12.00-15.50) min], and incision closure times [22.00 (20.00-23.50) min] (all p < 0.005). Postoperative outcomes also showed significant differences, with longer durations of drain removal (77.08 ± 18.16 h) and hospitalization for Type III [5.00 (5.00-6.00) d] (all p < 0.05). Additionally, Type I had a larger tumor diameter than the others (p = 0.009) and pT stage differed significantly between the subtypes (p = 0.020). CONCLUSIONS: The novel renal hilar tumor classification system is capable of differentiating the surgical difficulty of RAPN and further offers personalized surgical steps tailored to each specific classification. It provides a meaningful tool for clinical practice.

Cellaca® PLX image cytometer as an alternative for immunophenotyping, GFP/RFP transfection efficiencies, and apoptosis analysis.

Cell and gene therapy is a fast-growing field for cancer therapeutics requiring reliable instrumentation and technologies. Key parameters essential for satisfying Chemistry Manufacturing and Controls criteria standards are routinely performed using flow cytometry. Recently, image cytometry was developed for cell characterization and cell-based assays but had not yet demonstrated sufficient sensitivity for surface marker detection. We developed the Cellaca® PLX image cytometry system and the respective methodologies required for immunophenotyping, GFP and RFP transfection/transduction efficiencies, and cell health analyses for routine cell characterization. All samples tested were compared directly to results from the CytoFLEX flow cytometer. PBMCs were stained with T-cell surface markers for immunophenotyping, and results show highly comparable CD3, CD4, and CD8 populations (within 5 %). GFP- or RFP-expressing cell lines were analyzed for transfection/transduction efficiencies, and the percentage positive cells and respective viabilities were equivalent on both systems. Staurosporine-treated Jurkat cells were stained for apoptotic markers, where annexin V and caspase-3 positive cells were within 5 % comparing both instruments. The proposed system may provide a complementary tool for performing routine cell-based experiments with improved efficiency and sensitivity compared to prior image cytometers, which may be significantly valuable to the cell and gene therapy field.

Solvothermal Preparation of Microporous Polyureas for Au(III) Adsorption.

The enrichment and recovery of gold from wastewater are an alternative method to obtain this noble metal, which benefits reducing hazardous emissions from the conventional ore mining process and reserving natural gold for sustainable development. Inspired by our previous work (Lei et al., Macromol. Rapid Comm. 2022, 2200712), four families of microporous polyureas (mPPUs) with a large surface area (690 m2 g-1) and abundant heteroatom sites have been prepared via the factor-optimized solvothermal protocol. The resultant sample NPU-A starting from 1,5-naphthalene diisocyanate (NDI) and tri(4-aminophenyl) amine (TAPA) exhibits the maximum Au(III) adsorption capacity of 1300 mg g-1 and high selectivity even when the Au(III) concentration is as low as 0.1 mg L-1. This study not only demonstrates the robustness of the high-throughput synthetic strategy but also promotes the investigation of the structure-activity correlation between the mPPU chemical structure and Au(III) adsorption performance.

α-Conotoxin recombinant protein ImI-AFP3 efficiently inhibits the growth and migration of lung cancer cells.

α-Conotoxin ImI is a selective antagonist of alpha7 nicotinic acetylcholine receptor (α7 nAChR) that is involved in cancer development. Human alpha fetoprotein domain 3 (AFP3) is a prototype of anticancer agents. In an effort to design drugs for anticancer treatments, we fused the ImI peptide to AFP3 as a fusion protein for testing. The fusion protein (ImI-AFP3) was highly expressed in the insect Bac-to-Bac system. The purified fusion protein was found to have improved anticancer activity and synergized with the drug gefitinib to inhibit the growth and migration of A549 and NCI-H1299 lung cancer cells. Our data have demonstrated that the recombinant protein ImI-AFP3 is a promising candidate for drug development to suppress lung cancer cell growth, especially to suppress hepatoid adenocarcinoma of the lung (HAL) cell growth.

Synthesis of 2-(Trifluoromethyl)-[1,2,4]triazolo[5,1-a]isoquinoline via Cycloaddition of C,N-Cyclic Azomethine Imine with CF3CN.

A [3 + 2] cycloaddition of C,N-cyclic azomethine imine with in situ-generated CF3CN for the construction of 2-(trifluoromethyl)-[1,2,4]triazolo[5,1-a]isoquinoline is reported. Remarkably, this process shows a broad substrate scope with excellent functional group tolerance, which is scalable and enables a practical route to a library of 2-(trifluoromethyl)-[1,2,4]triazolo[5,1-a]isoquinoline derivatives in moderate to good yields.

Advances in uremic toxin detection and monitoring in the management of chronic kidney disease progression to end-stage renal disease.

Patients with end-stage kidney disease (ESKD) rely on dialysis to remove toxins and stay alive. However, hemodialysis alone is insufficient to completely remove all/major uremic toxins, resulting in the accumulation of specific toxins over time. The complexity of uremic toxins and their varying clearance rates across different dialysis modalities poses significant challenges, and innovative approaches such as microfluidics, biomarker discovery, and point-of-care testing are being investigated. This review explores recent advances in the qualitative and quantitative analysis of uremic toxins and highlights the use of innovative methods, particularly label-mediated and label-free surface-enhanced Raman spectroscopy, primarily for qualitative detection. The ability to analyze uremic toxins can optimize hemodialysis settings for more efficient toxin removal. Integration of multiple omics disciplines will also help identify biomarkers and understand the pathogenesis of ESKD, provide deeper understanding of uremic toxin profiling, and offer insights for improving hemodialysis programs. This review also highlights the importance of early detection and improved understanding of chronic kidney disease to improve patient outcomes.

High-Throughput SARS-CoV-2 Antiviral Testing Method Using the Celigo Image Cytometer.

The COVID-19 pandemic has created a worldwide public health crisis that has since resulted in 6.8 million reported deaths. The pandemic prompted the immediate response of researchers around the world to engage in rapid vaccine development, surveillance programs, and antiviral testing, which resulted in the delivery of multiple vaccines and repurposed antiviral drug candidates. However, the emergence of new highly transmissible SARS-CoV-2 variants has renewed the desire for discovering new antiviral drug candidates with high efficacy against the emerging variants of concern. Traditional antiviral testing methods employ the plaque-reduction neutralization tests (PRNTs), plaque assays, or RT-PCR analysis, but each assay can be tedious and time-consuming, requiring 2-3 days to complete the initial antiviral assay in biologically relevant cells, and then 3-4 days to visualize and count plaques in Vero cells, or to complete cell extractions and PCR analysis. In recent years, plate-based image cytometers have demonstrated high-throughput vaccine screening methods, which can be adopted for screening potential antiviral drug candidates. In this work, we developed a high-throughput antiviral testing method employing the Celigo Image Cytometer to investigate the efficacy of antiviral drug candidates on SARS-CoV-2 infectivity using a fluorescent reporter virus and their safety by measuring the cytotoxicity effects on the healthy host cell line using fluorescent viability stains. Compared to traditional methods, the assays defined here eliminated on average 3-4 days from our standard processing time for antiviral testing. Moreover, we were able to utilize human cell lines directly that are not typically amenable to PRNT or plaque assays. The Celigo Image Cytometer can provide an efficient and robust method to rapidly identify potential antiviral drugs to effectively combat the rapidly spreading SARS-CoV-2 virus and its variants during the pandemic.

A Multiplex Assay to Simultaneously Monitor Apoptosis and Necrosis Using the Cellaca® PLX Image Cytometer.

Apoptosis is the programmed cell death pathway that is critical for maintaining homeostasis, in which cancer cells can evade to ensure survival. For pharmaceutical drug discovery, it is important to characterize and compare different cancer therapeutics (i.e., small molecules, antibody drugs, cell therapies) that can initiate the process of apoptosis, enabling the identification of potential therapeutic candidates. In this work, we developed and demonstrated a multiplex detection method for monitoring apoptosis and necrosis with Annexin V, Caspase-3, and Propidium Iodide (PI) using the Cellaca® PLX Image Cytometer (Revvity Health Sciences, Inc., Lawrence, MA). First, apoptosis was induced in Jurkat and K562 cell lines with staurosporine over the course of 24 h, where apoptosis and necrosis were assessed at 0, 1, 1.5, 2, 4, 20, and 24 h timepoints. Samples were stained with Hoechst 33342 (total dye), Annexin V-APC (early-stage apoptosis), Caspase-3 488 (late-stage apoptosis), and PI (necrosis) at each timepoint and evaluated using image cytometry. Results showed that apoptotic factors and cascades were successfully detected along the pathway from early- to late-stage apoptosis, and ultimately necrosis. A clear trend was observed analyzing apoptotic and necrotic populations during the first 1.5 h, showing differences of up to ~15% in single Annexin V+ and Caspase-3+ populations in treated Jurkat cells, however, a significant increase in double positive apoptotic/necrotic cells for Annexin V+PI+ and Capase-3+PI+ was not observed until 20 h. Upon further analysis between apoptotic populations only, Annexin V+ only populations were higher than Caspase-3+ only populations by up to ~20% between 0 and 1.5 h. Conversely, K562 cells did not exhibit a notable change in apoptotic and necrotic populations due to low sensitivity to staurosporine. The proposed image cytometric detection method may provide an effective and efficient tool for rapid and reliable simultaneous detection of early- late-stage apoptosis, and necrosis. Therefore, allowing researchers to better characterize and screen potential cancer therapeutic drug candidates for their treatment efficacy in a higher throughput manner.

Monomer-Recyclable Polyester from CO2 and 1,3-Butadiene.

Synthesis of monomer-recyclable polyesters solely from CO2 and bulk olefins holds great potential in significantly reducing CO2 emissions and addressing the issue of plastic pollution. Due to the kinetic disadvantage of direct copolymerization of CO2 and bulk olefins compared to homopolymerization of bulk olefins, considerable research attention has been devoted to synthesis of polyester via the ring-opening polymerization (ROP) of a six-membered disubstituted lactone intermediate, 1,2-ethylidene-6-vinyl-tetrahydro-2H-pyran-2-one (𝜹-L), obtained from telomerization of CO2 and 1,3-butadiene. However, the conjugate olefin on the six-membered ring of 𝜹-L leads to serious Michael addition side reactions. Thus, the selective ROP of 𝜹-L, which can precisely control the repeating unit for the production of polyesters potentially amenable to efficient monomer recycling, remains an unresolved challenge. Herein, the first example of selective ROP of 𝜹-L is reported using a combination of organobase and N,N'-Bis[3,5-bis(trifluoromethyl)phenyl]urea as the catalytic system. Systematic modifications of the substituent of the urea show that the presence of electron-deficient 3,5-bis(trifluoromethyl)-phenyl groups is the key to the extraordinary selectivity of ring opening over Michael addition. Efficient monomer recovery of oligo(𝜹-L) is also achieved under mild catalytic conditions.

Bismuth-Containing Quadruple Therapy for Helicobacter pylori Eradication: A Randomized Clinical Trial of 10 and 14 Days.

BACKGROUND: Bismuth-containing quadruple therapy is the first-line treatment for eradicating Helicobacter pylori (H. pylori). The optimal duration for H. pylori eradication using bismuth-containing quadruple therapy remains controversial. Therefore, we aimed to compare the clinical effects of the 10- and 14-day bismuth-containing quadruple treatment regimen to eradicate H. pylori. METHODS: Treatment-naïve patients with H. pylori infection (n = 1300) were enrolled in this multicenter randomized controlled study across five hospitals in China. They were randomized into 10- or 14-day treatment groups to receive bismuth-containing quadruple therapy as follows: vonoprazan 20 mg twice daily; bismuth 220 mg twice daily; amoxicillin 1000 mg twice daily; and either clarithromycin 500 mg twice daily or tetracycline 500 mg four times daily. At least 6 weeks after treatment, we performed a 13C-urea breath test to evaluate H. pylori eradication. RESULTS: The per-protocol eradication rates were 93.22% (564/605) and 93.74% (569/607) (p < 0.001) and the intention-to-treat eradication rates were 88.62% (576/650) and 89.38% (581/650) (p = 0.007) for the 10- and 14-day regimens, respectively. Incidence of adverse effects was lower in patients who received 10- vs. 14 days of treatment (22.59% vs. 28.50%, p = 0.016). We observed no significant differences in the compliance to treatment or the discontinuation of therapy because of severe adverse effects between the groups. CONCLUSION: Compared with the 14-day bismuth-containing quadruple regimens, the 10-day regimen demonstrated a non-inferior efficacy and lower incidence of adverse effects. Therefore, the 10-day regimen is safe and tolerated and could be recommended for H. pylori eradication (NCT05049902).

Deep learning model for pleural effusion detection via active learning and pseudo-labeling: a multisite study.

BACKGROUND: The study aimed to develop and validate a deep learning-based Computer Aided Triage (CADt) algorithm for detecting pleural effusion in chest radiographs using an active learning (AL) framework. This is aimed at addressing the critical need for a clinical grade algorithm that can timely diagnose pleural effusion, which affects approximately 1.5 million people annually in the United States. METHODS: In this multisite study, 10,599 chest radiographs from 2006 to 2018 were retrospectively collected from an institution in Taiwan to train the deep learning algorithm. The AL framework utilized significantly reduced the need for expert annotations. For external validation, the algorithm was tested on a multisite dataset of 600 chest radiographs from 22 clinical sites in the United States and Taiwan, which were annotated by three U.S. board-certified radiologists. RESULTS: The CADt algorithm demonstrated high effectiveness in identifying pleural effusion, achieving a sensitivity of 0.95 (95% CI: [0.92, 0.97]) and a specificity of 0.97 (95% CI: [0.95, 0.99]). The area under the receiver operating characteristic curve (AUC) was 0.97 (95% DeLong's CI: [0.95, 0.99]). Subgroup analyses showed that the algorithm maintained robust performance across various demographics and clinical settings. CONCLUSION: This study presents a novel approach in developing clinical grade CADt solutions for the diagnosis of pleural effusion. The AL-based CADt algorithm not only achieved high accuracy in detecting pleural effusion but also significantly reduced the workload required for clinical experts in annotating medical data. This method enhances the feasibility of employing advanced technological solutions for prompt and accurate diagnosis in medical settings.

Berberine hydrochloride delays citrus sour rot mainly by disrupting carbohydrate and energy metabolism of Geotrichum citri-aurantii spores.

Citrus sour rot is a common postharvest citrus disease caused by Geotrichum citri-aurantiiti, which has led to enormous economic losses, particularly during rainy seasons. In this study, we aimed to clarify the impact of berberine hydrochloride (BH), the hydrochloride form of an isoquinoline alkaloid, on the control efficiency of citrus sour rot and its antifungal mode against G. citri-aurantii. Results demonstrated that BH markedly impede the propagation of G. citri-aurantii by delaying the spores development from dormant stage into swollen and germinating stages, with the MIC and MFC value of 0.08 and 0.16 g L-1, respectively. When the artificially inoculated citrus fruit in control group were totally rotted, the disease incidence of BH-treated groups decreased by 35.00%-73.30%, which effectively delayed the disease progression and almost did not negatively affect fruit quality. SEM observation, CFW and PI staining images revealed that BH caused significant damage to both the cell membrane and cell wall of G. citri-aurantii spores, whereas only the cell membrane of the mycelium was affected. The impact of cell wall was related to the block of chitin and ß-1,3-glucan synthesis. Transcriptome results and further verification proved that 0.5 × MIC BH treatment affected the glycolysis pathway and TCA cycle mainly by inhibiting the production of acetyl-CoA and pyruvate. Subsequently, the activities of key enzymes declined, resulting in a further decrease in ATP levels, ultimately inhibiting the germination of spores. In conlusion, BH delays citrus sour rot mainly by disrupting carbohydrate and energy metabolism of G. citri-aurantii spores.

Remarkably Deep Moiré Potential for Intralayer Excitons in MoSe2/MoS2 Twisted Heterobilayers.

A moiré superlattice formed in twisted van der Waals bilayers has emerged as a new tuning knob for creating new electronic states in two-dimensional materials. Excitonic properties can also be altered drastically due to the presence of moiré potential. However, quantifying the moiré potential for excitons is nontrivial. By creating a large ensemble of MoSe2/MoS2 heterobilayers with a systematic variation of twist angles, we map out the minibands of interlayer and intralayer excitons as a function of twist angles, from which we determine the moiré potential for excitons. Surprisingly, the moiré potential depth for intralayer excitons is up to ∼130 meV, comparable to that for interlayer excitons. This result is markedly different from theoretical calculations based on density functional theory, which show an order of magnitude smaller moiré potential for intralayer excitons. The remarkably deep intralayer moiré potential is understood within the framework of structural reconstruction within the moiré unit cell.

Mixed ensiling plus nitrate destroy fiber structure of rape straw, increase degradation, and reduce methanogenesis through in vitro ruminal fermentation.

BACKGROUND: Better utilization of rape straw can provide alternative strategies for sustainable ruminant and food production. The research reported here investigated changes in the carbohydrate composition of rape straw as a result of mixed ensiling with whole-crop corn or inoculated with nitrate, and the consequent effects on ruminal fermentation through in vitro batch culture. The three treatments included: rape straw and corn silage (RSTC), and ensiling treatment of rape straw with whole-crop corn (RSIC) or with calcium nitrate inoculation (RSICN). RESULTS: Ensiling treatment of rape straw and whole-crop corn or plus nitrate enriched lactic acid bacteria and lactate. The treatments broke the fiber surface connections of rape straw, leading to higher neutral detergent soluble (NDS) content and lower fiber content. Ensiling treatments led to greater (P < 0.05) dry matter degradation (DMD), molar proportions of propionate and butyrate, relative abundance of the phylum Bacteroidetes and genus Prevotella, and lower (P < 0.05) methane production in terms of g kg-1 DMD, molar proportions of acetate, and lower acetate to propionate ratio than the RSTC treatment. The RSICN treatment led to the lowest (P < 0.05) hydrogen concentration and methane production among the three treatments. CONCLUSION: Ensiling treatments of rape straw and whole-crop corn destroy the micro-structure of rape straw, promote substrate degradation by enriching the phylum Bacteroidetes and the genus Prevotella, and decrease methane production by favoring propionate and butyrate production. Nitrate inoculation in the ensiling treatment of rape straw and whole-crop corn further decreases methane production without influencing substrate degradation by providing an additional hydrogen sink. © 2023 Society of Chemical Industry.

Cucurbitacin E Exerts Anti-Proliferative Activity via Promoting p62-Dependent Apoptosis in Human Non-Small-Cell Lung Cancer A549 Cells.

EGFR tyrosine kinase inhibitors (TKIs) are the first-line treatment for advanced EGFR-mutated non-small-cell lung cancer (NSCLC). However, NSCLC patients with wild-type EGFR and KRAS mutation are ineligible for EGFR-TKIs. Therefore, the discovery of new therapeutic agents is urgently needed for NSCLC patients who cannot receive targeted therapies. Natural products possess tremendous chemical diversity and have been extensively investigated for their anticancer activity. In this study, we found that Cucurbitacin E (Cu E), a triterpene of cucurbitacins widely presented in the edible plants of the Cucurbitaceae family, significantly inhibits the viability and proliferation of A549 cells that harbor wild-type EGFR and KRAS mutation. Our results revealed that Cu E increases cell-cycle arrest at G2/M and subG1 phase. Mechanistically, Cu E significantly inhibits the phosphorylation and protein levels of regulatory proteins and hinders G2/M cell-cycle progression. Meanwhile, the treatment of Cu E resulted in DNA damage response and apoptosis. For the first time, we observed that Cu E induces incomplete autophagy as evidenced by increased LC3B-II expression and p62-accumulation. Knockdown of p62 rescued the cells from Cu E-mediated anti-proliferative effect, apoptosis, DNA damage, and ROS production. These findings suggest that Cu E is a promising drug candidate for NSCLC.

Correlation of LI-RADS 3 or 4 Observations with Histopathologic Diagnosis in Patients with Cirrhosis.

Patients with cirrhosis are high risk for developing hepatocellular carcinoma (HCC) and warrant surveillance using abdominal ultrasound and α-fetoprotein.1 Those with positive surveillance results should undergo diagnostic evaluation with multiphase computed tomography (CT) or magnetic resonance imaging (MRI). The LI-RADS system is an evidence-based system to classify observations on CT or MRI in at-risk patients, ranging from LR-1 (definite benign) to LR-5 (definite HCC), with LR-3 and LR-4 observations being intermediate risk for HCC.2 LR-3 and LR-4 observations are observed on CT or MRI in more than one-fourth of patients undergoing HCC surveillance and have a high, yet variable, risk for progression to HCC.3 Approximately one-third of patients with LR-3 observations and more than two-thirds of LR-4 observations develop HCC, and surveillance strategies vary widely in practice.4,5 Variation in radiographic appearance and natural history of these observations suggests that this may be a heterogeneous group of patients; however, their histopathology has not been well described. Herein, we correlated imaging findings and explant histopathology from liver transplant recipients with at least 1 LR-3 or LR-4 observation on CT or MRI within 6 months preceding transplantation.