Design and synthesis of novel ß-carboline-bisindole hybrids as potential anticancer agents.

We are reporting a short and convenient pathway for the synthesis of novel ß-carboline-bisindole hybrid compounds from relatively cheap and commercially available chemicals such as tryptamine, dialdehydes and indoles. These newly designed compounds can also be prepared in high yields with the tolerance of many functional groups under mild conditions. Notably, these ß-carboline-bisindole hybrid compounds exhibited some promising applications as anticancer agents against the three common cancer cell lines MCF-7 (breast cancer), SK-LU-1 (lung cancer), and HepG2 (liver cancer). The two best compounds 5b and 5g inhibited the aforementioned cell lines with the same range of the reference Ellipticine at less than 2 µM. A molecular docking study to gain more information about the interactions between the synthesized molecules and the kinase domain of the EGFR was performed. Therefore, this finding can have significant impacts on the development of future research in medicinal chemistry and drug discovery.

Falciform technique in laparoscopic revision of distal catheter obstruction: an evaluation.

Background: Ventriculoperitoneal (VP) shunting is a cornerstone treatment for hydrocephalus, a condition characterized by the abnormal accumulation of cerebrospinal fluid in the ventricles of the brain. Despite its efficacy, this procedure is associated with various complications, among which distal catheter obstruction poses significant challenges. This study aimed to evaluate the effectiveness of the 'falciform technique' in laparoscopic revision of distal catheter obstructions, offering a novel approach to mitigate this prevalent issue. Materials and methods: This study retrospectively analyzed 28 patients with VP shunt distal catheter obstructions who underwent laparoscopy-assisted shunt revision between January 2016 and June 2022. All of these were done using the 'falciform technique' with the fixation of the distal catheter to the falciform ligament in supra-hepatic space. Results: The most common etiology of primary shunt surgery was hydrocephalus, followed by intracranial hemorrhage (42.9%) and traumatic brain injury (32.1%). Normal pressure hydrocephalus occurs in 14.3% of cases. Fifteen patients (53.6%) required revision surgery within 1 year of index surgery. Thirteen patients (46.4%) underwent revision surgery more than 1 year after the index surgery, either as a first revision or subsequent revision. The average surgery time was 32.1±14.7 min and hospital stay was 4.2±1.8 days. After a mean follow-up period of at 20.3±8.7 months, except for three patients who died from other causes (two patients due to pneumonia and one due to exhaustion), there were no shunt-related complications in the remaining 25 patients. Conclusions: Laparoscopy with the application of 'falciform technique' is a safe and highly effective method in distal catheter obstruction revision following VP shunt.

Laparoscopic versus open total gastrectomy for T4a gastric cancer: a propensity score-matched analysis of long-term outcomes.

Evidence of implementation of laparoscopic total gastrectomy (LTG) for surgical T4a stage (sT4a) gastric cancer (GC) remains inadequate. This study aimed to compare short- and long-term outcomes of LTG versus open total gastrectomy (OTG) for sT4a GC. This retrospective cohort study was conducted using data from patients with sT4a GC underwent total gastrectomy from 2014 to 2020. Short-term outcomes included operative characteristics and postoperative complications. Long-term oncological outcomes focused on 3-, and 5-year overall survival (OS) and disease-free survival (DFS). Propensity score matching (PSM) was applied to reduce potential biases in baseline characteristics between groups. There was a total of 161 patients, in which 96 underwent LTG and 65 underwent OTG. After PSM, both groups consisted of 51 patients each, with balanced baseline characteristics. There were no significant differences between the two groups regarding blood loss, length of proximal resected margin, postoperative hospital stays, and overall and major postoperative complications. Most of the complications were classified as minor according to the Clavien-Dindo classification. Operating time was significantly longer in the LTG group (mean: 257 min vs. 231 min, p = 0.006). LTG was superior to OTG groups in time to flatus (mean: 3.0 days vs 3.9 days, p < 0.001). Five-year OS and DFS rates were similar between the two groups (44% and 33% vs. 43% and 28% in the LTG and OTG groups, respectively). Our findings indicate that LTG is a feasible and safe technique, exhibiting comparable long-term oncological outcomes to OTG for sT4a GC. LTG may be an acceptable alternative to OTG for the treatment of sT4a GC.

Enhancing catalytic activity of CuCoFe-layered double oxide towards peroxymonosulfate activation by coupling with biochar derived from durian peel for antibiotic degradation: The role of C=O in biochar and underlying mechanism of built-in electric field.

CuCoFe-LDO/BCD was successfully synthesized from CuCoFe-LDH and biochar derived from durian shell (BCD). Ciprofloxacin (CFX) degraded more than 95% mainly by O2•- and 1O2 in CuCoFe-LDO/BCD(2/1)/PMS system within 10 min with a rate constant of 0.255 min-1, which was 14.35 and 2.66 times higher than those in BCD/PMS and CuCoFe-LDO/PMS systems, respectively. The catalytic system exhibited good performance over a wide pH range (3-9) and high degradation efficiency of other antibiotics. Built-in electric field (BIEF) driven by large difference in the work function/Fermi level ratio between CuCoFe-LDO and BCD accelerated continuous electron transfer from CuCoFe-LDO to BCD to result in two different microenvironments with opposite charges at the interface, which enhanced PMS adsorption and activation via different directions. As a non-radical, 1O2 was mainly generated via PMS activation by C=O in BCD. The presence of C=O in BCD resulted in an increase in atomic charge of C in C=O and redistributed the charge density of other C atoms. As a result, strong adsorption of PMS at C atom in C=O and other C with a high positive charge was favorable for 1O2 generation, whereas an enhanced adsorption of PMS at negatively charged C accounted for the generation of •OH and SO4•-. After adsorption, electrons in C of BCD became deficient and were fulfilled with those transferred from CuCoFe-LDO driven by BIEF, which ensured the high catalytic activity of CuCoFe-LDO/BCD. O2•-, on the other hand, was generated via several pathways that involved in the transformation of •OH and SO4•- originated from PMS activation by the transition of metal species in CuCoFe-LDO and negatively charged C in BCD. This study proposed a new idea of fabricating a low-cost metal-LDH and biomass-derived catalyst with a strong synergistic effect induced by BIEF for enhancing PMS activation and antibiotic degradation.

Effects of montmorillonite on the loading and release of Piper betle L. extract applied for wound dressing based on chitosan/polyvinyl alcohol.

In this study, we investigate the influence of montmorillonite (MMT) on the loading and release of Piper betle L. extract (PLE)-a medicinal herb containing active secondary metabolites with antibacterial, antioxidant, and anti-inflammatory effects. MMT (1 %, 3 %, 5 %) was blended into the chitosan/polyvinyl alcohol (CS/PVA) biocomposite film by the solution evaporation method, and then PLE was loaded onto this biocomposite using the immersion method. The tensile strength and the ability to absorb exudates of the CS/PVA film improved with the increase in MMT content. The MMT 3 % film was considered to have the best properties: good mechanical properties with a tensile strength of 27.44 ± 0.27 MPa and elongation at break of 14.57 ± 0.30 %, potential for wound dressing due to its ability to absorb wound exudate (swelling degree 61.70 ± 0.30 %) and a suitable water vapor transmission rate (1999 ± 47 g/m2·d). The presence of MMT (1 %, 3 %, 5 %) in the CS/PVA film led to an increase in the PLE loading efficiency of the films compared to the film without MMT, up to 1.65, 1.73, and 1.87 times, respectively. The MMT 3 % and 5 % films also exhibited a sustained PLE release effect for up to 24 h. MMT increased PLE bioavailability through bioactivity tests: antibacterial activity against both E. coli and S. aureus, antioxidant activity, effective healing of 2nd-degree burn wounds, and biocompatibility with the L929 fibroblasts cell line. The combination of physicochemical properties and biological activities proved that the MMT/PLE drug delivery system based on the CS/PVA biocomposite is promising for wound dressing.

Sticky Hard Sphere Model for Characterizing Tumor Microstructure via Quantitative Ultrasound.

The use of the structure function (SF) to model inter-scatterer contribution to ultrasonic scattering is a major step to improve the capability and accuracy of quantitative ultrasound (QUS) and tissue characterization. However, existing QUS-based SF models rely on the hard-sphere (HS) model, which is limited in its applicability for complex scatterer distributions in real tissue. This paper introduces the sticky hard-sphere (SHS) model for QUS and tissue characterization, which considers a very short-range attractive potential that accounts for the adhesive nature of biological cells and yields a new parameter called stickiness. Herein, the analytical SF expression is presented for monodisperse scatterer size and validated using simulations of scatterer distributions with varying degrees of grouping and volume fractions (0.16, 0.32, and 0.40) over the frequency range from 15 to 110 MHz. The SHS model is applied to three mammary tumor types with differing spatial distributions of tumor cells. The histology-derived SF is computed by considering the nuclei as the main sources of scattering. The results show that the SHS model provides more accurate scatterer radius and volume fraction estimates than the HS model when fitted to histology-derived SF versus frequency curves. Furthermore, the new stickiness parameter provided by SHS is sensitive to the grouping structure in tumor cell distribution. This stickiness parameter, combined with the radius and volume fraction estimated from the SHS model, enables better differentiation between different tumor types than using the radius and volume fraction obtained from the HS model. This study demonstrates the potential of the SHS model to improve QUS tissue characterization.

The Prevalence of Anemia Among Vietnamese Children: A Systematic Review and Meta-Analysis.

While anemia constitutes a prevalent health issue among children in Vietnam, comprehensive aggregate data remain scarce. Consequently, the objective of this meta-analysis is to establish the pooled prevalence of anemia in the pediatric population of Vietnam. A comprehensive systematic search of existing prevalence studies was conducted up until June 2022, encompassing databases such as PubMed, Scopus, and the Cochrane Library, as well as reference list analysis. Pooled prevalence estimates, along with 95% confidence intervals (CIs), were calculated using a random-effects model. Publication bias was assessed using the Egger regression test and funnel plot inspection. Subgroup analyses were performed to identify potential variations in anemia prevalence across study groups. The pooled prevalence estimate for anemia among children under 10-year-olds amounted to 35.5% (95% CI = [23.9, 49.1]). Notably, gender-specific analyses unveiled distinct prevalence rates, with 37.8% among males and 33.4% among females. Furthermore, variations in anemia prevalence among Vietnamese children were evident across different demographic strata, encompassing gender, age groups, and rural or poor rural residency. The calculated pooled prevalence of anemia among children in Vietnam revealed a significant burden. Addressing this issue necessitates targeted interventions within specific regions and the implementation of government policies aligned with global targets for the eradication of childhood anemia.

Bio-Inspired Sensory Receptors for Artificial-Intelligence Perception.

In the era of artificial intelligence (AI), there is a growing interest in replicating human sensory perception. Selective and sensitive bio-inspired sensory receptors with synaptic plasticity have recently gained significant attention in developing energy-efficient AI perception. Various bio-inspired sensory receptors and their applications in AI perception are reviewed here. The critical challenges for the future development of bio-inspired sensory receptors are outlined, emphasizing the need for innovative solutions to overcome hurdles in sensor design, integration, and scalability. AI perception can revolutionize various fields, including human-machine interaction, autonomous systems, medical diagnostics, environmental monitoring, industrial optimization, and assistive technologies. As advancements in bio-inspired sensing continue to accelerate, the promise of creating more intelligent and adaptive AI systems becomes increasingly attainable, marking a significant step forward in the evolution of human-like sensory perception.

The influence of attributes on community preferences regarding antibiotic treatment: evidence from a discrete choice model.

Antibiotic resistance (AR) rates in Vietnam are among the highest in Asia, and recent infections due to multi-drug resistance in the country have caused thousands of deaths each year. This study investigated a Vietnamese community's preferences for antibiotic treatment and its knowledge and attitudes regarding antibiotics. A discrete choice experiment-based survey was developed and administered to the population of interest. The respondents were given sociodemographic-, knowledge- and attitude-related items and 17 pairs of choice tasks. Two hypothetical options were included in each choice task. Latent class analysis was conducted to determine the differences among the respondents' preferences. Among 1,014 respondents, 805 (79.4%) gave valid questionnaires. A three-latent-class model with four covariates (age, healthcare-related education or career, occupation, and attitude classifications) was used in the analysis. All five attributes significantly influenced the respondents' decisions. The majority, including young employed respondents with non-healthcare-related work or education, found treatment failure more important. Older respondents who had healthcare-related education/careers and/or appropriate antibiotic use- and antibiotics resistance-related attitudes, regarded contribution to antibiotic resistance as an important attribute in selecting antibiotic treatments. Unemployed individuals with correct knowledge identified the cost of antibiotic treatment as the most essential decision-making factor. Findings suggest minimal antibiotic impact on resistance; only 7.83% view it as amajor concern. The respondents exhibited substantial preference heterogeneity, and the general Vietnamese public had poor knowledge of and attitudes toward antibiotic use and antibiotic resistance. This study emphasizes the need for individual responsibility for antibiotic resistance and appropriate antibiotic use.

Initiation of acute pancreatitis in mice is independent of fusion between lysosomes and zymogen granules.

The co-localization of the lysosomal protease cathepsin B (CTSB) and the digestive zymogen trypsinogen is a prerequisite for the initiation of acute pancreatitis. However, the exact molecular mechanisms of co-localization are not fully understood. In this study, we investigated the role of lysosomes in the onset of acute pancreatitis by using two different experimental approaches. Using an acinar cell-specific genetic deletion of the ras-related protein Rab7, important for intracellular vesicle trafficking and fusion, we analyzed the subcellular distribution of lysosomal enzymes and the severity of pancreatitis in vivo and ex vivo. Lysosomal permeabilization was performed by the lysosomotropic agent Glycyl-L-phenylalanine 2-naphthylamide (GPN). Acinar cell-specific deletion of Rab7 increased endogenous CTSB activity and despite the lack of re-distribution of CTSB from lysosomes to the secretory vesicles, the activation of CTSB localized in the zymogen compartment still took place leading to trypsinogen activation and pancreatic injury. Disease severity was comparable to controls during the early phase but more severe at later time points. Similarly, GPN did not prevent CTSB activation inside the secretory compartment upon caerulein stimulation, while lysosomal CTSB shifted to the cytosol. Intracellular trypsinogen activation was maintained leading to acute pancreatitis similar to controls. Our results indicate that initiation of acute pancreatitis seems to be independent of the presence of lysosomes and that fusion of lysosomes and zymogen granules is dispensable for the disease onset. Intact lysosomes rather appear to have protective effects at later disease stages.

Organophosphate Pesticide Exposure: Effect on Farmers' Sperm Quality in the Mekong Delta, Vietnam.

OBJECTIVES: Using pesticides in the An Giang province is widespread. However, studies on the health effect of organophosphate pesticide have not been updated within the past 12 years. This study aimed to assess exposure to organophosphate pesticides and their effects on sperm quality among farmers in the An Giang Province, Mekong Delta, Vietnam. METHODS: During the winter - spring crop season of December 2021 to February 2022, a cross-sectional study was conducted on farmers aged 18 to 60 years-old based on seven communes' health checkup programs. The pesticide spray group included farmers who had sprayed pesticides in the previous week and had a history of working in agriculture for more than 2 years. The control group was defined as those who lived in the same community, had not worked in agriculture, and had never sprayed pesticides. Demographic characteristics and blood, urine, and semen samples were collected and analyzed. RESULTS: Data for 184 eligible participants were analyzed, including 116 farmers in the pesticide spray group and 68 non-farmers in the control group. Pesticide spray contributed to a decrease in the sperm quality index of 6.253 units (95% CI, 4.472-8.749). Increasing each pseudocholinesterase (PChE) unit (kIU/L) was associated with an increase of 1.181 units in the sperm quality index (95% CI, 0.757-0.947). CONCLUSIONS: Preventive methods for organophosphate pesticide exposure, such as administrative controls, engineering controls, substitution, and personal protective equipment should be applied to control health risks. In the An Giang setting, personal protective equipment is feasible, but most types of equipment are not used. The immediate priority is to determine the cause of personal protective equipment not being used and to find solutions to encourage people to use them.

Enhanced photoreduction efficiency of Cr(VI) driven by visible light in a new Zr-based metal-organic framework modified by hydroxyl groups.

While metal-organic framework (MOF) photocatalysts have demonstrated a unique Cr(VI) photoreduction capability in recent decades, their performance is still insufficient for practical applications because of their low Cr(VI) uptake and poor visible light response. To cope with these drawbacks, a new OH-modified Zr-based MOF, termed HCMUE-1, was successfully prepared via a solvothermal method in this work. The complete characterization of HCMUE-1 was performed through various techniques, including powder X-ray diffraction (PXRD), Raman spectroscopy, Fourier transform infrared (FT-IR), thermogravimetric analysis and differential scanning calorimetry (TGA-DSC), scanning electron microscopy combined with energy-dispersive X-ray (SEM-EDX), and X-ray photoelectron spectroscopy (XPS). The obtained data exhibited the excellent Cr(VI) photoreduction efficiency of HCMUE-1, reaching up to 98% after 90 min and almost 100% after 120 min under visible light illumination in a low acidic medium. Noteworthily, HCMUE-1 retained the same Cr(VI) removal rate for at least seven cycles without considerable loss. Further experimental investigations demonstrated that the structural stability and surface morphology of HCMUE-1 were retained after photoreduction. Moreover, the photocatalytic reduction mechanism of Cr(VI) to Cr(III) was interpreted through a series of systematic experimental measurements. These results indicate that HCMUE-1 possesses potential as an efficient photocatalyst for reducing toxic Cr(VI) species from wastewater in real-life conditions.

Recent Developments in Materials for Physical Hydrogen Storage: A Review.

The depletion of reliable energy sources and the environmental and climatic repercussions of polluting energy sources have become global challenges. Hence, many countries have adopted various renewable energy sources including hydrogen. Hydrogen is a future energy carrier in the global energy system and has the potential to produce zero carbon emissions. For the non-fossil energy sources, hydrogen and electricity are considered the dominant energy carriers for providing end-user services, because they can satisfy most of the consumer requirements. Hence, the development of both hydrogen production and storage is necessary to meet the standards of a "hydrogen economy". The physical and chemical absorption of hydrogen in solid storage materials is a promising hydrogen storage method because of the high storage and transportation performance. In this paper, physical hydrogen storage materials such as hollow spheres, carbon-based materials, zeolites, and metal-organic frameworks are reviewed. We summarize and discuss the properties, hydrogen storage densities at different temperatures and pressures, and the fabrication and modification methods of these materials. The challenges associated with these physical hydrogen storage materials are also discussed.

Role of indocyanine green fluorescence imaging for evaluating blood supply in the gastric conduit via the substernal route after McKeown minimally invasive esophagectomy.

BACKGROUND: Anastomotic leakage (AL) is a determining factor of morbidity and mortality after esophagectomy. Adequate perfusion of the gastric conduit is crucial for AL prevention. This study aimed to determine whether intraoperative angiography using indocyanine green (ICG) fluorescence improves the incidence of AL after McKeown minimally invasive esophagectomy (MIE) with gastric conduit via the substernal route (SR). METHODS: This retrospective cohort study included 120 patients who underwent MIE with gastric conduit via SR for esophageal cancer between February 2019 and April 2023. Of 120 patients, 88 experienced intraoperative angiography using ICG (ICG group), and 32 patients experienced intraoperative angiography without ICG (no-ICG group). Baseline characteristics and operative outcomes, including AL as the main concern, were compared between the 2 groups. In addition, the outcomes among patients in the ICG group with different levels of fluorescence intensity were compared. RESULTS: The ICG and no-ICG groups were comparable in baseline characteristics and operative outcomes. There was no significant difference between the 2 groups regarding the rate of AL (31.0% vs 37.5%; P = .505), median dates of AL (9 vs 9 days; P = .810), and severity of AL (88.9%, 11.11%, and 0.0% vs 66.7%, 16.7%, and 16.7% for grades I, II, and III, respectively; P = .074). Patients in the ICG group with lower intensity of ICG had higher rates of leakage (24.6%, 39.3%, and 100% in levels I, II, and III of ICG intensity, respectively; P = .04). CONCLUSION: The use of ICG did not seem to reduce the rate of AL. However, abnormal intensity of ICG fluorescence was associated with a higher rate of AL, which implies a predictive potential.

Utilizing a High-Performance Piezoelectric Nanocomposite as a Self-Activating Component in Piezotronic Artificial Mechanoreceptors.

Challenges such as poor dispersion and insufficient polarization of BaTiO3 (BTO) nanoparticles (NPs) within poly(vinylidene fluoride-co-trifluoroethylene) (P(VDF-TrFE)) composites have hindered their piezoelectricity, limiting their uses in pressure sensors, nanogenerators, and artificial sensory synapses. Here, we introduce a high-performance piezoelectric nanocomposite material consisting of P(VDF-TrFE)/modified-BTO (mBTO) NPs for use as a self-activating component in a piezotronic artificial mechanoreceptor. To generate high-performance piezoelectric nanocomposite materials, the surface of BTO is hydroxylated, followed by the covalent attachment of (3-aminopropyl)triethoxysilane to improve the dispersibility of mBTO NPs within the P(VDF-TrFE) matrix. We also aim to enhance the crystallization degree of P(VDF-TrFE), the efficiency characteristics of mBTO, and the poling efficiency, even when incorporating small amounts of mBTO NPs. The piezoelectric potential mechanically induced from the P(VDF-TrFE)/mBTO NPs nanocomposite was three times greater than that from P(VDF-TrFE) and twice as high as that from the P(VDF-TrFE)/BTO NPs nanocomposite. The piezoelectric potential generated by mechanical stimuli on the piezoelectric nanocomposite was utilized to activate the synaptic ionogel-gated field-effect transistor for the development of self-powered piezotronics artificial mechanoreceptors on a polyimide substrate. The device successfully emulated fast-adapting (FA) functions found in biological FA mechanoreceptors. This approach has great potential for applications to future intelligent tactile perception technology.

Dynamics-driven allosteric stimulation of diguanylate cyclase activity in a red light-regulated phytochrome.

Sensor-effector proteins integrate information from different stimuli and transform this into cellular responses. Some sensory domains, like red-light responsive bacteriophytochromes, show remarkable modularity regulating a variety of effectors. One effector domain is the GGDEF diguanylate cyclase catalyzing the formation of the bacterial second messenger cyclic-dimeric-guanosine monophosphate. While critical signal integration elements have been described for different phytochromes, a generalized understanding of signal processing and communication over large distances, roughly 100 Å in phytochrome diguanylate cyclases, is missing. Here we show that dynamics-driven allostery is key to understanding signal integration on a molecular level. We generated protein variants stabilized in their far-red-absorbing Pfr state and demonstrated by analysis of conformational dynamics using hydrogen-deuterium exchange coupled to mass spectrometry that single amino acid replacements are accompanied by altered dynamics of functional elements throughout the protein. We show that the conformational dynamics correlate with the enzymatic activity of these variants, explaining also the increased activity of a non-photochromic variant. In addition, we demonstrate the functional importance of mixed Pfr/intermediate state dimers using a fast-reverting variant that still enables wild-type-like fold-changes of enzymatic stimulation by red light. This supports the functional role of single protomer activation in phytochromes, a property that might correlate with the non-canonical mixed Pfr/intermediate-state spectra observed for many phytochrome systems. We anticipate our results to stimulate research in the direction of dynamics-driven allosteric regulation of different bacteriophytochrome-based sensor-effectors. This will eventually impact design strategies for the creation of novel sensor-effector systems for enriching the optogenetic toolbox.

Targeting the TNF/IAP pathway synergizes with anti-CD3 immunotherapy in T-cell acute lymphoblastic leukemia.

ABSTRACT: T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive hematological malignancy. Current treatments, based on intensive chemotherapy regimens provide overall survival rates of ∼85% in children and <50% in adults, calling the search of new therapeutic options. We previously reported that targeting the T-cell receptor (TCR) in T-ALL with anti-CD3 (αCD3) monoclonal antibodies (mAbs) enforces a molecular program akin to thymic negative selection, a major developmental checkpoint in normal T-cell development; induces leukemic cell death; and impairs leukemia progression to ultimately improve host survival. However, αCD3 monotherapy resulted in relapse. To find out actionable targets able to re-enforce leukemic cells' vulnerability to αCD3 mAbs, including the clinically relevant teplizumab, we identified the molecular program induced by αCD3 mAbs in patient-derived xenografts derived from T-ALL cases. Using large-scale transcriptomic analysis, we found prominent expression of tumor necrosis factor α (TNFα), lymphotoxin α (LTα), and multiple components of the "TNFα via NF-κB signaling" pathway in anti-CD3-treated T-ALL. We show in vivo that etanercept, a sink for TNFα/LTα, enhances αCD3 antileukemic properties, indicating that TNF/TNF receptor (TNFR) survival pathways interferes with TCR-induced leukemic cell death. However, suppression of TNF-mediated survival and switch to TNFR-mediated cell death through inhibition of cellular inhibitor of apoptosis protein-1/2 (cIAP1/2) with the second mitochondrial-derived activator of caspases (SMAC) mimetic birinapant synergizes with αCD3 to impair leukemia expansion in a receptor-interacting serine/threonine-protein kinase 1-dependent manner and improve mice survival. Thus, our results advocate the use of either TNFα/LTα inhibitors, or birinapant/other SMAC mimetics to improve anti-CD3 immunotherapy in T-ALL.

Billroth-II modified with hinged anti-peristaltic afferent loop versus Roux-en-Y reconstruction after distal gastrectomy for gastric cancer: A propensity-score match analysis.

BACKGROUND: This study aimed to evaluate the effectiveness of modified Billroth-II with a hinged anti-peristaltic afferent loop by comparing it with the Roux-en-Y method. METHODS: We retrospectively analyzed 344 patients with gastric cancer who underwent distal gastrectomy between 2016 and 2021. Propensity score matching was conducted to balance baseline characteristics. RESULTS: After propensity score matching, there were 117 patients in each group. The Billroth-II group was significantly better regarding operating time (184.7 vs 225.3 minutes), postoperative hospital stays (7.9 vs 9.2 days), and time to semi-solid diet tolerance (2.8 vs 3.8 days). The Billroth-II group demonstrated comparable results with the Roux-en-Y group in weight loss, hemoglobin changes, reflux esophagitis, food residue, and gastritis severity. Presentation of bile in gastric remnant was significantly higher in the Billroth-II group (42.9% vs 10.3%). CONCLUSION: There were no significant differences in functional outcomes between Billroth-II and Roux-en-Y reconstructions. The Billroth-II was superior to Roux-en-Y in operating time, hospital stays, and time to semi-solid diet tolerance. The Billroth-II could be considered an acceptable alternative reconstruction after distal gastrectomy.

Reconstitution of cytolinker-mediated crosstalk between actin and vimentin.

Cell shape and motility are determined by the cytoskeleton, an interpenetrating network of actin filaments, microtubules, and intermediate filaments. The biophysical properties of each filament type individually have been studied extensively by cell-free reconstitution. By contrast, the interactions between the three cytoskeletal networks are relatively unexplored. They are coupled via crosslinkers of the plakin family such as plectin. These are challenging proteins for reconstitution because of their giant size and multidomain structure. Here we engineer a recombinant actin-vimentin crosslinker protein called 'ACTIF' that provides a minimal model system for plectin, recapitulating its modular design with actin-binding and intermediate filament-binding domains separated by a coiled-coil linker for dimerisation. We show by fluorescence and electron microscopy that ACTIF has a high binding affinity for vimentin and actin and creates mixed actin-vimentin bundles. Rheology measurements show that ACTIF-mediated crosslinking strongly stiffens actin-vimentin composites. Finally, we demonstrate the modularity of this approach by creating an ACTIF variant with the intermediate filament binding domain of Adenomatous Polyposis Coli. Our protein engineering approach provides a new cell-free system for the biophysical characterization of intermediate filament-binding crosslinkers and for understanding the mechanical synergy between actin and vimentin in mesenchymal cells.