Grade 3/4 Adverse Event Costs of Immuno-oncology Combination Therapies for Previously Untreated Advanced Renal Cell Carcinoma.

BACKGROUND: Despite 4 approved combination regimens in the first-line setting for advanced renal cell carcinoma (aRCC), adverse event (AE) costs data are lacking. MATERIALS AND METHODS: A descriptive analysis on 2 AE cost comparisons was conducted using patient-level data for the nivolumab-based therapies and published data for the pembrolizumab-based therapies. First, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib using data from the CheckMate 214 (median follow-up [mFU]: 13.1 months), CheckMate 9ER (mFU: 12.8 months), and KEYNOTE-426 (mFU: 12.8 months) trials, respectively. Second, grade 3/4 AE costs were compared between nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib using data from the CheckMate 214 (mFU: 26.7 months), CheckMate 9ER (mFU: 23.5 months), and KEYNOTE-581 (mFU: 26.6 months) trials, respectively. Per-patient costs for all-cause and treatment-related grade 3/4 AEs with corresponding any-grade AE rates ≥ 20% were calculated based on the Healthcare Cost and Utilization Project database and inflated to 2020 US dollars. RESULTS: Per-patient all-cause grade 3/4 AE costs for nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + axitinib were $2703 vs. $4508 vs. $5772, and treatment-related grade 3/4 AE costs were $741 vs. $2722 vs. $4440 over ~12.8 months of FU. For nivolumab + ipilimumab vs. nivolumab + cabozantinib vs. pembrolizumab + lenvatinib, per-patient all-cause grade 3/4 AE costs were $3120 vs. $5800 vs. $9285, while treatment-related grade 3/4 AE costs were $863 vs. $3162 vs. $5030 over ~26.6 months of FU. CONCLUSION: Patients with aRCC treated with first-line nivolumab-based therapies had lower grade 3/4 all-cause and treatment-related AE costs than pembrolizumab-based therapies, suggesting a more favorable cost-benefit profile.

Semiparametric estimation of restricted mean survival time as a function of restriction time.

The restricted mean survival time (RMST) is an appealing measurement in clinical or epidemiological studies with censored survival outcome and receives a lot of attention in the past decades. It provides a useful alternative to the Cox model for evaluating the covariate effect on survival time. The covariate effect on RMST usually varies with the restriction time. However, existing methods cannot address this problem properly. In this article, we propose a semiparametric framework that directly models RMST as a function of the restriction time. Our proposed model adopts a widely-used proportional form, enabling the estimation of RMST predictions across an interval using a unified model. Furthermore, the covariate effect for multiple restriction time points can be derived simultaneously. We develop estimators based on estimating equations theories and establish the asymptotic properties of the proposed estimators. The finite sample properties of the estimators are evaluated through extensive simulation studies. We further illustrate the application of our proposed method through the analysis of two real data examples. Supplementary Material are available online.

Key genes and potential drugs in age-related hearing loss: transcriptome analysis of cochlear hair cells in old mice.

This study aimed to dig new molecular mechanisms and medications for age-related hearing loss (ARHL or presbycusis) by extracting common results of publicly available datasets. Based on five datasets (GSE153882, GSE121856, GSE98070, GSE45026, and GSE98071) in studies of cochlear hair cells, we explored the interrelationships among presbycusis-related genes, including gene interactions, enrichment analysis, miRNA-mRNA matching pairs, and potential new drugs. Together, there were 25 common increased mRNAs. A total of 183 drugs can simultaneously target 11 of these mRNAs. In the interaction network, hub genes included: Cbln1, Prl, Mpp6 and Gh. Meanwhile, there were 74 common decreased mRNAs. The hub genes include Cdkn1a, Egr1, and Ctgf. After de-duplication, the 25 common increased mRNAs had 946 matched miRNAs, with 34 decreased ones; and the 74 decreased mRNAs had 1164 matched miRNAs, with 26 increased ones. Between the inhibitors of increased mRNAs and enhancers of decreased mRNAs, there were 26 common drugs. Besides, we discovered six key genes that may play a crucial role in the onset of presbycusis. In conclusion, by jointly analyzing multiple datasets, we found 25 common increased mRNAs (e.g., Cbln1, Prl, Mpp6 and Gh) and 74 common decreased mRNAs (Cdkn1a, Egr1, and Ctgf), as well as 34 potential therapeutic miRNAs and 26 pathogenic miRNAs, and three candidate drugs (calcitriol, diclofenac, and diethylstilbestrol). They may provide new targets and strategies for mechanistic and therapeutic studies in ARHL.

Answering medical questions in Chinese using automatically mined knowledge and deep neural networks: an end-to-end solution.

BACKGROUND: Medical information has rapidly increased on the internet and has become one of the main targets of search engine use. However, medical information on the internet is subject to the problems of quality and accessibility, so ordinary users are unable to obtain answers to their medical questions conveniently. As a solution, researchers build medical question answering (QA) systems. However, research on medical QA in the Chinese language lags behind work on English-based systems. This lag is mainly due to the difficulty of constructing a high-quality knowledge base and the underutilization of medical corpora in the Chinese language. RESULTS: This study developed an end-to-end solution to implement a medical QA system for the Chinese language with low cost and time. First, we created a high-quality medical knowledge graph from hospital data (electronic health/medical records) in a nearly automatic manner that trained a supervised model based on data labeled using bootstrapping techniques. Then, we designed a QA system based on a memory-based neural network and attention mechanism. Finally, we trained the system to generate answers from the knowledge base and a QA corpus on the internet. CONCLUSIONS: Bootstrapping and deep neural network techniques can construct a knowledge graph from electronic health/medical records with satisfactory precision and coverage. Our proposed context bridge mechanisms perform training with a variety of language features. Our QA system can achieve state-of-the-art quality in answering medical questions with constrained topics. As we evaluated, complex Chinese language processing techniques, such as segmentation and parsing, were not necessary for practice and complex architectures were not necessary to build the QA system. Lastly, we created an application using our method for internet QA usage.

Temporal trends of adverse events and costs of nivolumab plus ipilimumab versus sunitinib in advanced renal cell carcinoma.

Aims: To assess grade 3/4 adverse events (AEs) and costs of first-line nivolumab plus ipilimumab versus sunitinib in advanced or metastatic renal cell carcinoma. Methods: Individual patient data from the all treated population in the CheckMate 214 trial (nivolumab plus ipilimumab, n = 547; sunitinib, n = 535) were used to calculate the number of AEs. AE unit costs were obtained from US 2017 Healthcare Cost and Utilization Project and inflated to 2020 values. Results: The proportion of patients experiencing grade 3/4 AEs decreased over time. Patients who received nivolumab plus ipilimumab had lower average per-patient all-cause grade 3/4 AE costs versus sunitinib (12-month: US$15,170 vs US$20,342; 42-month: US$19,096 vs US$27,473). Conclusion: Treatment with nivolumab plus ipilimumab was associated with lower grade 3/4 AE costs than sunitinib.

Immunotherapy combinations are now accepted as safe and effective first-line treatment options for advanced or metastatic renal cell carcinoma. This study used patient data from the CheckMate 214 clinical trial to evaluate the temporal trends and costs related to grade 3/4 adverse events (AEs) among patients treated with nivolumab plus ipilimumab versus sunitinib. We found that the proportion of patients experiencing grade 3/4 AEs decreased over time and that patients treated with nivolumab plus ipilimumab had lower AE costs compared with those treated with sunitinib (at 42 months: US$19,096 vs US$27,473 per patient). As such, nivolumab plus ipilimumab may represent a treatment option that may reduce both the clinical and economic burden among patients with advanced or metastatic renal cell carcinoma.

Cystine-glutamate antiporter xCT deficiency suppresses tumor growth while preserving antitumor immunity.

T cell-invigorating cancer immunotherapies have near-curative potential. However, their clinical benefit is currently limited, as only a fraction of patients respond, suggesting that these regimens may benefit from combination with tumor-targeting treatments. As oncogenic progression is accompanied by alterations in metabolic pathways, tumors often become heavily reliant on antioxidant machinery and may be susceptible to increases in oxidative stress. The cystine-glutamate antiporter xCT is frequently overexpressed in cancer and fuels the production of the antioxidant glutathione; thus, tumors prone to redox stress may be selectively vulnerable to xCT disruption. However, systemic inhibition of xCT may compromise antitumor immunity, as xCT is implicated in supporting antigen-induced T cell proliferation. Therefore, we utilized immune-competent murine tumor models to investigate whether cancer cell expression of xCT was required for tumor growth in vivo and if deletion of host xCT impacted antitumor immune responses. Deletion of xCT in tumor cells led to defective cystine uptake, accumulation of reactive oxygen species, and impaired tumor growth, supporting a cancer cell-autonomous role for xCT. In contrast, we observed that, although T cell proliferation in culture was exquisitely dependent on xCT expression, xCT was dispensable for T cell proliferation in vivo and for the generation of primary and memory immune responses to tumors. These findings prompted the combination of tumor cell xCT deletion with the immunotherapeutic agent anti-CTLA-4, which dramatically increased the frequency and durability of antitumor responses. Together, these results identify a metabolic vulnerability specific to tumors and demonstrate that xCT disruption can expand the efficacy of anticancer immunotherapies.

Ambient sulfur dioxide and hospital expenditures and length of hospital stay for respiratory diseases: A multicity study in China.

BACKGROUND: Ambient sulfur dioxide (SO2) has been associated with morbidity and mortality of respiratory diseases, however, its effect on length of hospital stays (LOS) and cost for these diagnoses remain unclear. METHODS: We collected hospital admission information for respiratory diseases from all 11 cities in the Shanxi Province of China during 2017-2019. We assessed individual-level exposure by using an inverse distance weighting approach based on geocoded residential addresses. A generalized additive model was built to delineate city-specific effects of SO2 on hospitalization, hospital expenditure, and length of hospital stay for respiratory diseases. The overall effects were obtained by random-effects meta-analysis. We further estimated the respiratory burden attributable to SO2 by comparing different reference concentrations. RESULTS: We observed significant effects of SO2 exposure on respiratory diseases. At the provincial level, each 10 µg/m3 increase in SO2 on lag03 was associated with a 0.63% (95% CI: 0.14-0.11) increase in hospital admission, an increase of 4.56 days (95% CI: 1.16-7.95) of hospital stay, and 3647.97 renminbi (RMB, Chinese money) (95% CI: 1091.05-6204.90) in hospital cost. We estimated about 6.13 (95% CI: 1.33-11.10) thousand hospital admissions, 65.77 million RMB (95% CI: 19.67-111.87) in hospital expenditure, and 82.13 (95% CI: 20.87-143.40) thousand days of hospital stay could have potentially been avoided had the daily SO2 concentrations been reduced to WHO's reference concentration (40 µg/m3). Variable values in correspondence with this reference concentration could reduce the hospital cost and LOS of each case by 52.67 RMB (95% CI: 15.75-89.59) and 0.07 days (95% CI: 0.02-0.117). CONCLUSION: This study provides evidence that short-term ambient SO2 exposure is an important risk factor of respiratory diseases, indicating that continually tightening policies to reduce SO2 levels could effectively reduce respiratory disease burden in Shanxi Province.

Ambient PM2.5 exposure and hospital cost and length of hospital stay for respiratory diseases in 11 cities in Shanxi Province, China.

BACKGROUND: Few studies have examined the effects of ambient particulate matter with an aerodynamic diameter less than or equal to 2.5 µm (PM2.5) on hospital cost and length of hospital stay for respiratory diseases in China. METHODS: We estimated ambient air pollution exposure for respiratory cases through inverse distance-weighted averages of air monitoring stations based on their residential address and averaged at the city level. We used generalised additive models to quantify city-specific associations in 11 cities in Shanxi and a meta-analysis to estimate the overall effects. We further estimated respiratory burden attributable to PM2.5 using the standards of WHO (25 µg/m3) and China (75 µg/m3) as reference. RESULTS: Each 10 µg/m3 increase in lag03 PM2.5 corresponded to 0.53% (95% CI: 0.33% to 0.73%) increase in respiratory hospitalisation, an increment of 3.75 thousand RMB (95% CI: 1.84 to 5.670) in hospital cost and 4.13 days (95% CI: 2.51 to 5.75) in length of hospital stay. About 9.7 thousand respiratory hospitalisations, 132 million RMB in hospital cost and 145 thousand days of hospital stay could be attributable to PM2.5 exposures using WHO's guideline as reference. We estimated that 193 RMB (95% CI: 95 to 292) in hospital cost and 0.21 days (95% CI: 0.13 to 0.30) in hospital stay could be potentially avoidable for an average respiratory case. CONCLUSION: Significant respiratory burden could be attributable to PM2.5 exposures in Shanxi Province, China. The results need to be factored into impact assessment of air pollution policies to provide a more complete indication of the burden addressed by the policies.

Magnetic amino-functionalized metal-organic frameworks as a novel solid support in ionic liquids-based effervescent tablets for efficient extraction of polycyclic aromatic hydrocarbons in milks.

Herein, a kind of novel multi-layer core-shell nanocomposites (NSPN) was prepared by employing SiO2 and polyvinylpyrrolidone (PVP) polymers as modifiers and amino-functionalized metal-organic frameworks (NH2-MIL101(Fe)) as coating. It was referred to as the NSPN and ILs-based effervescence-assisted dispersive solid-phase microextraction, hereafter abbreviated as NIE-DSM. In terms of extraction efficiency, SiO2 and PVP as modifiers and NH2-MIL(Fe) as coating onto the surface of NiFe2O4 cores played a synergistically enhancing effect on adsorption/extraction. Effervescent tablets were prepared by integrating the NSPN magnetic nanoparticles as adsorbents with imidazolium-based ionic liquids (ILs) as extractants as well as acidic and alkaline sources. Under vigorous dispersion of CO2 bubbles, the NIE-DSM method realized the goal of rapidly diffusing and separating the adsorbent/extractant (~3 min) without needing conventional vortexing or centrifugation step. Consequently, the NIE-DSM approach combined dispersion and adsorption/extractant in a synchronous way. Under optimized conditions, the NIE-DSM/HPLC-FLD method gave low limits of detection (0.008-0.034 µg kg-1) and satisfactory extraction recoveries (74.1-101.6%) for five polycyclic aromatic hydrocarbons (PAHs; fluorene, anthracene, pyrene, chrysene and benzo(a)pyrene) in milk samples. The intra-day and inter-day precision, expressed as relative standard deviations, was < 5.9% and 6.5%, respectively, demonstrating a high precision. Owing to no requirement for electrical power, this method shows great potential for outdoor monitoring of trace-level PAHs in food matrices.

Economic burden associated with tuberous sclerosis complex in patients with epilepsy.

OBJECTIVES: Data on the economic burden associated with tuberous sclerosis complex (TSC) among patients with epilepsy in the United States (US) are limited. This study aimed to assess all-cause and epilepsy-related healthcare resource utilization (HRU) and healthcare costs in the US among patients with epilepsy and TSC compared with patients with epilepsy but without TSC. METHODS: This retrospective study was conducted using the Symphony Health Solutions claims database (April 1, 2017-June 30, 2019). Patients with ≥1 medical claim with a diagnosis code representing epilepsy or seizures were assigned to the cohort with TSC if they had ≥1 medical claim for TSC; the remaining patients were assigned to the cohort without TSC. Patients in the cohort with TSC were exactly matched 1:5 on demographics to patients in the cohort without TSC. All-cause and epilepsy-related HRU, medical charges, prescription drug costs, and the use of antiepileptic drugs (AEDs) were compared between the matched cohorts over the 1-year study period. RESULTS: A total of 2028 patients with epilepsy and TSC were matched to 10,140 patients with epilepsy but without TSC. Patients with TSC were more likely to have a diagnosis code for refractory epilepsy (38.7% vs. 10.2%, p < 0.001) and more likely to have used an AED (89.5% vs. 71.2%, p < 0.001) than patients without TSC over the study period. On average, patients with TSC received 2.1 distinct AEDs versus 1.3 distinct AEDs among patients without TSC. Compared with patients without TSC, patients with TSC had numerically but not statistically higher incidence rates of all-cause outpatient, clinic, office, and other visits; significantly lower rates of all-cause inpatient and emergency room visits (p < 0.001); and statistically significantly higher incidence rates of epilepsy-related outpatient, inpatient, office, and other visits (p ≤ 0.001). All-cause prescription drug costs were significantly higher among patients with TSC than patients without TSC (cost difference per patient: $14,179, p < 0.001). All-cause medical service charges were numerically higher for patients with TSC, but the differences were not statistically significant (charge difference per patient: $4293 for medical services, p = 0.707). Epilepsy-related costs were significantly higher for patients with TSC; the cost difference per patient was $14,639 for prescription costs (p < 0.001), and the charge difference per patient was $16,838 for medical charges (p = 0.019). CONCLUSION: The results of this study underscore the high epilepsy-related HRU and costs incurred by patients with epilepsy and TSC relative to those incurred by patients with epilepsy but without TSC.

Inference for restricted mean survival time as a function of restriction time under length-biased sampling.

The restricted mean survival time (RMST) is often of direct interest in clinical studies involving censored survival outcomes. It describes the area under the survival curve from time zero to a specified time point. When data are subject to length-biased sampling, as is frequently encountered in observational cohort studies, existing methods cannot estimate the RMST for various restriction times through a single model. In this article, we model the RMST as a continuous function of the restriction time under the setting of length-biased sampling. Two approaches based on estimating equations are proposed to estimate the time-varying effects of covariates. Finally, we establish the asymptotic properties for the proposed estimators. Simulation studies are performed to demonstrate the finite sample performance. Two real-data examples are analyzed by our procedures.

Perforation of the terminal ileum caused by brucellosis: A case report.

Brucellosis, caused by gram-negative coccobacilli of the genus Brucella, is a zoonotic disease with bone and joint complications being common. However, acute abdomen with intestinal perforation is rare. We present a case of a 69-year-old man diagnosed with acute diffuse peritonitis and intestinal perforation due to Brucella infection. Surgical intervention revealed ileocecal perforation with wheel spoke-like necrosis. The patient underwent partial resection, ileum closure, and ileostomy. Positive blood culture and Brucella agglutination confirmed the diagnosis. Targeted tetracycline and aminoglycoside treatment led to recovery.

Highly Thermally Conductive Super-Aligned Boron Nitride Nanotube Films for Flexible Electronics Thermal Management.

Flexible electronics toward high integration, miniaturization, and multifunctionality, leading to a dramatic increase in power density. However, the low thermal conductivity of flexible substrates impedes efficient heat dissipation and device performance improvement. In this work, we propose a template-assisted chemical conversion strategy for obtaining boron nitride nanotube (BNNT) films with high thermal conductivity and great flexibility. Aligned carbon nanotube (CNT) films have been adopted as templates; a low-temperature chemical conversion followed by a high-temperature annealing has been carried out to produce a highly ordered BNNT film. Benefiting from the high orientation order, the BNNT film exhibits an exceptional thermal conductivity of 45.5 W m-1 K-1 and presents excellent heat dissipation capability, much superior to the commonly used polyimide film. Furthermore, the BNNT film demonstrated excellent flexibility and high insulation resistance. The test of integration with film resistors demonstrated its potential as a thermally conductive substrate for electronics cooling. This work provides a solution for the effective thermal management of flexible electronics.

Self-powered photoelectrochemical aptasensor for fumonisin B1 detection based on a Z-scheme ZnIn2S4/WO3 photoanode.

The incidence of esophageal cancer is positively associated with fumonisin contamination. It is necessary to develop methods for the rapid detection of fumonisins. In this work, a self-powered photoelectrochemical aptamer sensor based on ZnIn2S4/WO3 photoanode and Au@W-Co3O4 photocathode is proposed for the sensitive detection of fumonisin B1 (FB1). Among them, under visible light irradiation, the Z-type heterostructure of ZnIn2S4/WO3 acts as a photoanode to improve the electron transfer rate, which contributes to the enhancement of the photocathode signal and lays the foundation for a wider detection range. The Au@W-Co3O4 photocathode as a sensing interface reduces the probability of false positives (comparison of anode sensing platforms). The PEC sensor has a good working performance in the detection range (10 pg/mL-1000 ng/mL) with a detection limit of 2.7 pg/mL (S/N = 3). In addition, the sensor offers good selectivity, stability and excellent recoveries in real sample analysis. This work is expected to play a role in the field of analyzing environmental toxins.

Lateral Heterostructure Formed by Highly Thermally Conductive Fluorinated Graphene for Efficient Device Thermal Management.

The continued miniaturization of chips demands highly thermally conductive materials and effective thermal management strategies. Particularly, the high-field transport of the devices built with 2D materials is limited by self-heating. Here a systematic control of heat flow in single-side fluorinated graphene (FG) with varying degrees of fluorination is reported, revealing a superior room-temperature thermal conductivity as high as 128 W m-1 K-1. Monolayer graphene/FG lateral heterostructures with seamless junctions are approached for device fabrication. Efficient in-plane heat removal paths from graphene channel to side FG are created, contributing significant reduction of the channel peak temperature and improvement in the current-carrying capability and power density. Molecular dynamics simulations indicate that the interfacial thermal conductance of the heterostructure is facilitated by the high degree of overlap in the phonon vibrational spectra. The findings offer novel design insights for efficient heat dissipation in micro- and nanoelectronic devices.

Gene Expression, Enzyme Activity, Nitrogen Use Efficiency, and Yield of Rice Affected by Controlled-Release Nitrogen.

Controlled- or slow-release urea can improve crop nitrogen use efficiencies and yields in many agricultural production systems. The effect of controlled-release urea on the relationships between levels of gene expression and yields has not been adequately researched. We conducted a 2 year field study with direct-seeded rice, which included treatments of controlled-release urea at four rates (120, 180, 240, and 360 kg N ha-1), a standard urea treatment (360 kg N ha-1), and a control treatment without applied nitrogen. Controlled-release urea improved the inorganic nitrogen concentrations of root-zone soil and water, functional enzyme activities, protein contents, grain yields, and nitrogen use efficiencies. Controlled-release urea also improved the gene expressions of nitrate reductase [NAD(P)H] (EC 1.7.1.2), glutamine synthetase (EC 6.3.1.2), and glutamate synthase (EC 1.4.1.14). With the exception of glutamate synthase activity, there were significant correlations among these indices. The results showed that controlled-release urea improved the content of inorganic nitrogen within the rice root zone. Compared with urea, the average enzyme activity of controlled-release urea increased by 50-200%, and the relative gene expression was increased by 3-4 times on average. The added soil nitrogen increased the level of gene expression, allowing enhanced synthesis of enzymes and proteins for nitrogen absorption and use. Hence, controlled-release urea improved the nitrogen use efficiency and the grain yield of rice. Controlled-release urea is an ideal nitrogen fertilizer showing great potential for improving rice production.

A Self-Powered UV Photodetector With Ultrahigh Responsivity Based on 2D Perovskite Ferroelectric Films With Mixed Spacer Cations.

Self-powered photodetectors (PDs) have the advantages of no external power requirement, wireless operation, and long life. Spontaneous ferroelectric polarizations can significantly increase built-in electric field intensity, showing great potential in self-powered photodetection. Moreover, ferroelectrics possess pyroelectric and piezoelectric properties, beneficial for enhancing self-powered PDs. 2D metal halide perovskites (MHPs), which have ferroelectric properties, are suitable for fabricating high-performance self-powered PDs. However, the research on 2D metal halide perovskites ferroelectrics focuses on growing bulk crystals. Herein, 2D ferroelectric perovskite films with mixed spacer cations for self-powered PDs are demonstrated by mixing Ruddlesden-Popper (RP)-type and Dion-Jacobson (DJ)-type perovskite. The (BDA0.7 (BA2 )0.3 )(EA)2 Pb3 Br10 film possesses, overall, the best film qualities with the best crystalline quality, lowest trap density, good phase purity, and obvious ferroelectricity. Based on the ferro-pyro-phototronic effect, the PD at 360 nm exhibits excellent photoelectric properties, with an ultrahigh peak responsivity greater than 93 A W-1 and a detectivity of 2.5 × 1015 Jones, together with excellent reproducibility and stability. The maximum responsivities can be modulated by piezo-phototronic effect with an effective enhancement ratio of 480%. This work will open up a new route of designing MHP ferroelectric films for high-performance PDs and offers the opportunity to utilize it for various optoelectronics applications.

Identification of the High-Affinity Potassium Transporter Gene Family (HKT) in Brassica U-Triangle Species and Its Potential Roles in Abiotic Stress in Brassica napus L.

Members of the high-affinity potassium transporter (HKT) protein family regulate the uptake and homeostasis of sodium and potassium ions, but little research describes their roles in response to abiotic stresses in rapeseed (Brassica napus L.). In this study, we identified and characterized a total of 36 HKT genes from the species comprising the triangle of U model (U-triangle species): B. rapa, B. nigra, B. oleracea, B. juncea, B. napus, and B. carinata. We analyzed the phylogenetic relationships, gene structures, motif compositions, and chromosomal distributions of the HKT family members of rapeseed. Based on their phylogenetic relationships and assemblage of functional domains, we classified the HKT members into four subgroups, HKT1;1 to HKT1;4. Analysis of the nonsynonymous substitutions (Ka), synonymous substitutions (Ks), and the Ka/Ks ratios of HKT gene pairs suggested that these genes have experienced strong purifying selective pressure after duplication, with their evolutionary relationships supporting the U-triangle theory. Furthermore, the expression profiles of BnaHKT genes varies among potassium, phytohormone and heavy-metal treatment. Their repression provides resistance to heavy-metal stress, possibly by limiting uptake. Our results systematically reveal the characteristics of HKT family proteins and their encoding genes in six Brassica species and lay a foundation for further exploration of the role of HKT family genes in heavy-metal tolerance.

Lutein-Based pH and Photo Dual-Responsive Novel Liposomes Coated with Ce6 and PTX for Tumor Therapy.

Liposomes are considered the best nanocarrier for delivering cancer drugs such as chlorin e6 (Ce6) and paclitaxel (PTX). However, the poor stability and non-selectivity release of liposomes may severely limit their further applications. In this study, based on the characteristics of lutein (L) photo-response and orthoester (OE) acid-response, stable and dual-responsive liposomes (Dr-lips) have been prepared. The Dr-lips exhibited a spherical shape with a uniform size of approximately 58.27 nm. Moreover, they displayed a zeta potential ranging from -45.45 to -28.25 mV and showed excellent storage stability, indicating stable colloidal properties. Additionally, they achieved high drug encapsulation rates, with 92.27% for PTX and 90.34% for Ce6, respectively. Meanwhile, under near-infrared (NIR) light at 660 nm, Ce6 plays a key role in accelerating the photodegradation rate of lutein and PEG-OE-L while also enhancing tissue penetration ability. Additionally, Dr-lips loaded with Ce6 and PTX not only displayed excellent pH and photo dual-responsiveness for targeted delivering and releasing but also showed remarkable reactive oxygen species (ROS) generation capacity and impressive anti-tumor activity in vitro. Therefore, it provides a novel strategy for optimizing stability and enhancing their targeted drug delivery of liposome.

Thermoresponsive Property of Poly(N,N-bis(2-methoxyethyl)acrylamide) and Its Copolymers with Water-Soluble Poly(N,N-disubstituted acrylamide) Prepared Using Hydrosilylation-Promoted Group Transfer Polymerization.

The group-transfer polymerization (GTP) of N,N-bis(2-methoxyethyl)acrylamide (MOEAm) initiated by Me2EtSiH in the hydrosilylation-promoted method and by silylketene acetal (SKA) in the conventional method proceeded in a controlled/living manner to provide poly(N,N-bis(2-methoxyethyl)acrylamide) (PMOEAm) and PMOEAm with the SKA residue at the α-chain end (MCIP-PMOEAm), respectively. PMOEAm-b-poly(N,N-dimethylacrylamide) (PDMAm) and PMOEAm-s-PDMAm and PMOEAm-b-poly(N,N-bis(2-ethoxyethyl)acrylamide) (PEOEAm) and PMOEAm-s-PEOEAm were synthesized by the block and random group-transfer copolymerization of MOEAm and N,N-dimethylacrylamide or N,N-bis(2-ethoxyethyl)acrylamide. The homo- and copolymer structures affected the thermoresponsive properties; the cloud point temperature (Tcp) increasing by decreasing the degree of polymerization (x). The chain-end group in PMOEAm affected the Tcp with PMOEAmx > MCIP-PMOEAmx. The Tcp of statistical copolymers was higher than that of block copolymers, with PMOEAmx-s-PDMAmy > PMOEAmx-b-PDMAmy and PMOEAmx-s-PEOEAmy > PMOEAmx-b-PEOEAmy.