Sonrotoclax overcomes BCL2 G101V mutation-induced venetoclax resistance in preclinical models of hematologic malignancy.

ABSTRACT: Venetoclax, the first-generation inhibitor of the apoptosis regulator B-cell lymphoma 2 (BCL2), disrupts the interaction between BCL2 and proapoptotic proteins, promoting the apoptosis in malignant cells. Venetoclax is the mainstay of therapy for relapsed chronic lymphocytic leukemia and is under investigation in multiple clinical trials for the treatment of various cancers. Although venetoclax treatment can result in high rates of durable remission, relapse has been widely observed, indicating the emergence of drug resistance. The G101V mutation in BCL2 is frequently observed in patients who relapsed treated with venetoclax and sufficient to confer resistance to venetoclax by interfering with compound binding. Therefore, the development of next-generation BCL2 inhibitors to overcome drug resistance is urgently needed. In this study, we discovered that sonrotoclax, a potent and selective BCL2 inhibitor, demonstrates stronger cytotoxic activity in various hematologic cancer cells and more profound tumor growth inhibition in multiple hematologic tumor models than venetoclax. Notably, sonrotoclax effectively inhibits venetoclax-resistant BCL2 variants, such as G101V. The crystal structures of wild-type BCL2/BCL2 G101V in complex with sonrotoclax revealed that sonrotoclax adopts a novel binding mode within the P2 pocket of BCL2 and could explain why sonrotoclax maintains stronger potency than venetoclax against the G101V mutant. In summary, sonrotoclax emerges as a potential second-generation BCL2 inhibitor for the treatment of hematologic malignancies with the potential to overcome BCL2 mutation-induced venetoclax resistance. Sonrotoclax is currently under investigation in multiple clinical trials.

Unveiling synergistic QTLs associated with slow wilting in soybean (Glycine max [L.] Merr.).

KEY MESSAGE: A stable QTL qSW_Gm10 works with a novel locus, qSW_Gm01, in a synergistic manner for controlling slow-wilting traits at the early vegetative stage under drought stress in soybean. Drought is one of the major environmental factors which limits soybean yield. Slow wilting is a promising trait that can enhance drought resilience in soybean without additional production costs. Recently, a Korean soybean cultivar SS2-2 was reported to exhibit slow wilting at the early vegetative stages. To find genetic loci responsible for slow wilting, in this study, quantitative trait loci (QTL) analysis was conducted using a recombinant inbred line (RIL) population derived from crossing between Taekwangkong (fast-wilting) and SS2-2 (slow-wilting). Wilting score and leaf moisture content were evaluated at the early vegetative stages for three years. Using the ICIM-MET module, a novel QTL on Chr01, qSW_Gm01 was identified, together with a previously known QTL, qSW_Gm10. These two QTLs were found to work synergistically for slow wilting of the RILs under the water-restricted condition. Furthermore, the SNP markers from the SoySNP50K dataset, located within these QTLs, were associated with the wilting phenotype in 30 diverse soybean accessions. Two genes encoding protein kinase 1b and multidrug resistance-associated protein 4 were proposed as candidate genes for qSW_Gm01 and qSW_Gm10, respectively, based on a comprehensive examination of sequence variation and gene expression differences in the parental lines under drought conditions. These genes may play a role in slow wilting by optimally regulating stomatal aperture. Our findings provide promising genetic resources for improving drought resilience in soybean and give valuable insights into the genetic mechanisms governing slow wilting.

RNA-seq profiling in leaf tissues of two soybean (Glycine max [L.] Merr.) cultivars that show contrasting responses to drought stress during early developmental stages.

Drought stress is the major environment constraint on soybean yield, and a variety of pathways underlie drought tolerance mechanisms. Transcriptomic profiling of two soybean cultivars, drought-tolerant SS2-2 and drought-sensitive Taekwang, was performed under normal and drought conditions to identify genes involved in drought tolerance. This revealed large differences in water loss during drought treatment. Genes involved in signaling, lipid metabolism, phosphorylation, and gene regulation were overrepresented among genes that were differentially expressed between cultivars and between treatments in each cultivar. The analysis revealed transcription factors from six families, including WRKYs and NACs, showed significant SS2-2-specific upregulation. Genes involved in stress defense pathways, including MAPK signaling, Ca2+ signaling, ROS scavenging, and NBS-LRR, were also identified. Expression of non-specific phospholipases, phospholipase D, and PHOSPHATIDYL INOSITOL MONOPHOSPHATE 5 KINASE (PIP5K), which act in the lipid-signaling pathway, was greatly increased in SS2-2. The roles of PIP5K in drought stress tolerance were confirmed in Arabidopsis thaliana. Arabidopsis pip5k mutants had significantly lower survival rates under drought stress than wild-type plants. This study identified additional elements in the mechanisms used by plants to protect themselves from drought stress and provides valuable information for the development of drought-tolerant soybean cultivars. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-023-01385-1.

The Correlation between Helicobacter pylori Immunoglobulin G Seropositivity and Plasma Homocysteine Levels in Adults.

Objectives: Helicobacter pylori (H. pylori) immunoglobulin G (IgG) seropositivity is prevalent, but its correlation with homocysteine (Hcy), a biomarker of vascular risk events, is unclear. This study is aimed at exploring the correlation of H. pylori IgG seropositivity and plasma Hcy levels in adults. Methods: Data was obtained from the National Health and Nutrition Examination Survey (NHANES) cycle 1999-2000. Hcy was measured by the Abbott homocysteine assay, and H. pylori IgG was measured by enzyme-linked immunosorbent assays. The weighted multiple logistic regression analyses with adjustments for potential confounders were conducted. Subgroup analyses stratified by gender, age, and race were performed. Results: A total of 4029 subjects aged 20-85 years were included. Population prevalence of H. pylori IgG seropositivity was 44.7% in the overall population with higher prevalence found in those with older age, Mexican Americans, lower education, and lower household income. Levels of plasma Hcy were not elevated in those with H. pylori IgG seropositivity versus seronegativity (ß -0.120 (-0.438, 0.199) P = 0.462). This difference was not significant after stratifying by gender and age. However, in the subgroup analyses stratified by race, a negative correlation between H. pylori seropositivity and plasma Hcy levels was observed in Mexican Americans (ß -0.802 (-1.253, -0.352) P < 0.001). Conclusions: H. pylori IgG seropositivity was not associated with plasma Hcy levels in the general population, but there may be a negative correlation in Mexican Americans. These findings provide new insights to advance the research of the link between plasma Hcy levels and stomach health.

Multi-Scale FPGA-Based Infrared Image Enhancement by Using RGF and CLAHE.

Infrared sensors capture thermal radiation emitted by objects. They can operate in all weather conditions and are thus employed in fields such as military surveillance, autonomous driving, and medical diagnostics. However, infrared imagery poses challenges such as low contrast and indistinct textures due to the long wavelength of infrared radiation and susceptibility to interference. In addition, complex enhancement algorithms make real-time processing challenging. To address these problems and improve visual quality, in this paper, we propose a multi-scale FPGA-based method for real-time enhancement of infrared images by using rolling guidance filter (RGF) and contrast-limited adaptive histogram equalization (CLAHE). Specifically, the original image is first decomposed into various scales of detail layers and a base layer using RGF. Secondly, we fuse detail layers of diverse scales, then enhance the detail information by using gain coefficients and employ CLAHE to improve the contrast of the base layer. Thirdly, we fuse the detail layers and base layer to obtain the image with global details of the input image. Finally, the proposed algorithm is implemented on an FPGA using advanced high-level synthesis tools. Comprehensive testing of our proposed method on the AXU15EG board demonstrates its effectiveness in significantly improving image contrast and enhancing detail information. At the same time, real-time enhancement at a speed of 147 FPS is achieved for infrared images with a resolution of 640 × 480.

A Real-Time FPGA Implementation of Infrared and Visible Image Fusion Using Guided Filter and Saliency Detection.

Taking advantage of the functional complementarity between infrared and visible light sensors imaging, pixel-level real-time image fusion based on infrared and visible light images of different resolutions is a promising strategy for visual enhancement, which has demonstrated tremendous potential for autonomous driving, military reconnaissance, video surveillance, etc. Great progress has been made in this field in recent years, but the fusion speed and quality of visual enhancement are still not satisfactory. Herein, we propose a multi-scale FPGA-based image fusion technology with substantially enhanced visual enhancement capability and fusion speed. Specifically, the source images are first decomposed into three distinct layers using guided filter and saliency detection, which are the detail layer, saliency layer and background layer. Fusion weight map of the saliency layer is subsequently constructed using attention mechanism. Afterwards weight fusion strategy is used for saliency layer fusion and detail layer fusion, while weight average fusion strategy is used for the background layer fusion, followed by the incorporation of image enhancement technology to improve the fused image contrast. Finally, high-level synthesis tool is used to design the hardware circuit. The method in the present study is thoroughly tested on XCZU15EG board, which could not only effectively improve the image enhancement capability in glare and smoke environments, but also achieve fast real-time image fusion with 55FPS for infrared and visible images with a resolution of 640 × 470.

A new sesquineolignan and four new neolignans isolated from the leaves of Piper betle, a traditional medicinal plant in Myanmar.

One new sesquineolignan, piperneolignan A (1), four new neolignans, piperneolignans B-E (2-5), and eight known compounds were isolated from the leaves of Piper betle (Piperaceae) collected from Myanmar. These new structures were determined by analysis of MS and NMR data, and the absolute configuration of piperneolignan A was elucidated by electronic circular dichroism (ECD) calculations. Piperneolignan A (1), piperneolignan B (2), hydroxychavicol (6), p-hydroxycinnamaldehyde (10), and diallylcatechol (13) possessed anti-inflammatory activity against nitric oxide (NO) production in lipopolysaccharide (LPS)-activated murine macrophage RAW 264.7 cells with IC50 values of 9.87, 45.94, 4.80, 26.40, and 40.45 µM, respectively, compared with the positive control NG-monomethyl-l-arginine (l-NMMA, IC50 = 33.84 µM). The two hydroxy groups in the structure of hydroxychavicol are essential for activity, and dimerization or trimerization of hydroxychavicol decreases activity.

Evaluation on Antidiabetic Properties of Medicinal Plants from Myanmar.

OBJECTIVES: To explore the effective and safe medicines for treating diabetes. METHODS: Hydroalcoholic extracts of 130 medicinal plants belonging to 66 families were evaluated using porcine pancreatic lipase (PPL) inhibition and glucose uptake methods together with a literature review. RESULTS: The extracts of 22 species showed the PPL inhibition activity; 18 extracts of 15 species stimulated glucose uptake in 3T3-L1 adipocytes. Among them, Mansonia gagei J.R. Drumm., Mesua ferrea L., and Centella asiatica (L.) Urb. exhibited both activities. The extracts of Caladium lindenii (André) Madison rhizomes and Azadirachta indica A. Juss. leaves presented the utmost lipase inhibitory activity with IC50 of 6.86 ± 0.25 and 11.46 ± 0.06 µg/mL, respectively. The extracts of Coptis teeta Wall. rhizomes and Croton tiglium L. seeds stimulated the maximum glucose uptake. Ten species are reported to have antidiabetic activity for the first time. Flavonoids and triterpenoids are the dominant antidiabetic compounds in selected medicinal plants from Myanmar. CONCLUSIONS: P. zeylanica, L. cubeba, H. crenulate, M. gagei, C. teeta, and M. ferrea are worthy to advance further study according to their strong antidiabetic activities and limited research on effects in in vivo animal studies, unclear chemical constitutes, and safety.

Genome-Wide Identification of OSC Gene Family and Potential Function in the Synthesis of Ursane- and Oleanane-Type Triterpene in Momordica charantia.

The triterpenes in bitter gourd (Momordica charantia) show a variety of medicinal activities. Oxidosqualene cyclase (OSC) plays an indispensable role in the formation of triterpene skeletons during triterpene biosynthesis. In this study, we identified nine genes encoding OSCs from bitter gourd (McOSC1-9). Analyses of their expression patterns in different tissues suggested that characteristic triterpenoids may be biosynthesized in different tissues and then transported. We constructed a hairy root system in which McOSC7 overexpression led to an increased accumulation of camaldulenic acid, enoxolone, and quinovic acid. Thus, the overexpression of McOSC7 increased the active components content in bitter gourd. Our data provide an important foundation for understanding the roles of McOSCs in triterpenoid synthesis.

Strategic white matter injury associated with long-term information processing speed deficits in mild traumatic brain injury.

Deficits in information processing speed (IPS) are among the earliest and most prominent cognitive manifestations in mild traumatic brain injury (mTBI). We investigated the impact of white matter fiber location on IPS outcome in an individual basis assessment. A total of 112 acute mild TBI with all CT negative underwent brain DTI and blood sampling for inflammation cytokines within 7 days postinjury and 72 age- and sex matched healthy controls with same assessments were enrolled. IPS outcome was assessed by the trail making test at 6-12 month postinjury in mild TBI. Fractional anisotropy (FA) features were extracted using a novel lesion-load analytical strategy to capture spatially heterogeneous white matter injuries and minimize implicit assumptions of uniform injury across diverse clinical presentations. Acute mild TBI exhibited a general pattern of increased and decreased FA in specific white matter tracts. The power of acute FA measures to identify patients developing IPS deficits with 92% accuracy and further improved to 96% accuracy by adding inflammation cytokines. The classifiers predicted individual's IPS and working memory ratings (r = .74 and .80, respectively, p < .001). The thalamo-cortical circuits and commissural tracts projecting or connecting frontal regions became important predictors. This prognostic model was also verified by an independent replicate sample. Our findings highlighted damage to frontal interhemispheric and thalamic projection fiber tracts harboring frontal-subcortical neuronal circuits as a predictor for processing speed performance in mild TBI.

Transcriptomic and biochemical analyses of the accumulation of sucrose in mungbean (Vigna radiata (L.) Wilczek) leaves after pod removal.

KEY MESSAGE: Synchronous pod maturity is critical for increasing grain yield. The candidate genes involved in synchronous pod maturity were identified through RNA-seq and HPLC. Mungbean (Vigna radiata [L.] Wilczek), an important source of carbohydrate and protein in Asia, is characterized by nonsynchronous pod maturity; consequently, harvesting is labor intensive. Because pod maturity is associated with synthesis and remobilization of sucrose, we examined changes in sucrose levels and transcriptome in leaf (source) tissues after pod (sink) removal using two genotypes, VC1973A and V2984; VC1973A had higher synchronicity in pod maturity than V2984. After pod removal, much higher number of pods were produced in V2984 than VC1973A. The sucrose content of leaf tissues significantly decreased in V2984 because it continued to utilize assimilates from leaves for producing new pods, but significantly increased in VC1973A because of the loss of sink. Transcriptome analysis revealed that the number of differentially expressed genes was approximately fourfold higher in VC1973A than in those of V2984 after pod removal. The expression of two paralogous genes (Vradi01g05010 and Vradi10g08240), encoding beta-glucosidase enzymes, significantly decreased in VC1973A after pod removal and was significantly lower in depodded VC1973A than depodded V2984, indicating these two genes may participate in sucrose utilization for seed development by regulating the level of glucose. The results of this study will help elucidate the genetic basis of synchronous pod maturity in mungbean and facilitate the development of new cultivars with synchronous pod maturity.

microRNA-26a-5p affects myocardial injury induced by coronary microembolization by modulating HMGA1.

Coronary microembolization (CME) occurs when atherosclerotic plaque debris is detached during the treatment of acute coronary syndrome with Percutaneous Coronary Intervention (PCI). The complications of distal microvascular embolism, including local myocardial inflammation, are the main causes of myocardial damage and are a strong predictor of poor long-term prognosis and major cardiac adverse events. microRNAs (miRNAs) are involved in the pathophysiological processes of cardiovascular inflammatory diseases. Dysregulation of microRNA (miR)-26a-5p, in particular, is associated with a variety of cardiovascular diseases. However, the role of miR-26a-5p in CME-induced myocardial injury is unclear. In this study, we developed an animal model of CME by injecting microembolic balls into the left ventricle of rats and found that miR-26a-5p expression decreased in myocardial tissue in response. Using a miR-26a-5p mimic, echocardiography, hematoxylin-eosin staining, and Western blot analysis we found that the diminished cardiac function and myocardial inflammation induced by CME is alleviated by miR-26a-5p overexpression. Furthermore, our results show that inhibitors of miR-26a-5p have the opposite effect. In addition, in vitro experiments using real-time PCR, Western blot analysis, and a dual luciferase reporter gene show that HMGA1 is a target gene of miR-26a-5p. Thus, overexpression of miR-26a-5p could be a novel therapy to improve CME-induced myocardial damage.

PMS1T, producing phased small-interfering RNAs, regulates photoperiod-sensitive male sterility in rice.

Phased small-interfering RNAs (phasiRNAs) are a special class of small RNAs, which are generated in 21- or 24-nt intervals from transcripts of precursor RNAs. Although phasiRNAs have been found in a range of organisms, their biological functions in plants have yet to be uncovered. Here we show that phasiRNAs generated by the photopheriod-sensetive genic male sterility 1 (Pms1) locus were associated with photoperiod-sensitive male sterility (PSMS) in rice, a germplasm that started the two-line hybrid rice breeding. The Pms1 locus encodes a long-noncoding RNA PMS1T that was preferentially expressed in young panicles. PMS1T was targeted by miR2118 to produce 21-nt phasiRNAs that preferentially accumulated in the PSMS line under long-day conditions. A single nucleotide polymorphism in PMS1T nearby the miR2118 recognition site was critical for fertility change, likely leading to differential accumulation of the phasiRNAs. This result suggested possible roles of phasiRNAs in reproductive development of rice, demonstrating the potential importance of this RNA class as regulators in biological processes.

Triterpenoids and Their Glycosides from Glinus Oppositifolius with Antifungal Activities against Microsporum Gypseum and Trichophyton Rubrum.

Four new triterpenoids, 3ß,12ß,16ß,21ß,22-pentahydroxyhopane (1), 12ß,16ß,21ß,22-tetrahydroxyhopan-3-one (2), 3-oxo-olean-12-ene-28,30-dioic acid (3), and 3ß-hydroxyoleana-11,13(18)-diene-28,30-dioic acid 30-methyl ester (4); 21 new triterpenoid saponins, glinusopposides A-U (5-25); and 12 known compounds (26-37) were isolated from the whole plants of Glinus oppositifolius. The structures of the new compounds were elucidated based on the analysis of one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR) and mass spectrometry (MS) data. All compounds from the plants were measured for antifungal activities against Microsporum gypseum and Trichophyton rubrum. Glinusopposide B (6), glinusopposide Q (21), glinusopposide T (24), and glinusopposide U (25) showed strong inhibitory activities against M. gypseum (MIC50 7.1, 6.7, 6.8, and 11.1 µM, respectively) and T. rubrum (MIC50 14.3, 13.4, 11.9, and 13.0 µM, respectively). For those active compounds with an oleanane skeleton, glycosylation (21-26) or oxidation (3) of 3-OH was helpful in increasing the activity; replacement of the 30-methyl group (29) by a carboxymethyl group (26) enhanced the activity; the presence of 11,13(18) double bonds (20) decreased the activity.

Efficacy of prophylactic probiotics in combination with antibiotics versus antibiotics alone for colorectal surgery: A meta-analysis of randomized controlled trials.

This meta-analysis aimed to determine whether prophylactic probiotics in combination with antibiotics are superior to antibiotics alone in the prevention of surgical site infection (SSI) after colorectal surgery. Fourteen trials involving 1524 participants were included. Compared with antibiotics alone, prophylactic probiotics in combination with antibiotics reduced the risk of SSI as well as other complications, shortened the cumulative duration of antibiotic therapy. Current evidence suggested that probiotics in combination with antibiotics could be recommended.

Coordinated regulation of vegetative and reproductive branching in rice.

Grasses produce tiller and panicle branching at vegetative and reproductive stages; the branching patterns largely define the diversity of grasses and constitute a major determinant for grain yield of many cereals. Here we show that a spatiotemporally coordinated gene network consisting of the MicroRNA 156 (miR156/)miR529/SQUAMOSA PROMOTER BINDING PROTEIN LIKE (SPL) and miR172/APETALA2 (AP2) pathways regulates tiller and panicle branching in rice. SPL genes negatively control tillering, but positively regulate inflorescence meristem and spikelet transition. Underproduction or overproduction of SPLs reduces panicle branching, but by distinct mechanisms: miR156 and miR529 fine-tune the SPL levels for optimal panicle size. miR172 regulates spikelet transition by targeting AP2-like genes, which does not affect tillering, and the AP2-like proteins play the roles by interacting with TOPLESS-related proteins (TPRs). SPLs modulate panicle branching by directly regulating the miR172/AP2 and PANICLE PHYTOMER2 (PAP2)/Rice TFL1/CEN homolog 1 (RCN1) pathways and also by integrating other regulators, most of which are not involved in tillering regulation. These findings may also have significant implications for understanding branching regulation of other grasses and for application in rice genetic improvement.

Licoflavonol is an inhibitor of the type three secretion system of Salmonella enterica serovar Typhimurium.

As an important food-borne human pathogen, Salmonella enterica serovar Typhimurium depends on its type III secretion system (T3SS) as a major virulence factor to cause disease all over the world. The T3SS secretes effector proteins to facilitate invasion into host cells. In this study, twenty prenylated flavonoids (1-20) were screened for their anti-T3SS activity, revealing that several analogs exhibited strong inhibitory effects on the secretion of Salmonella pathogenicity island 1 (SPI-1)-associated effector proteins without affecting the growth of bacteria and the secretion of the flagellar protein FliC. Among the flavonoids 1-20, licoflavonol (20) exhibited a strong inhibitory effect on the secretion of the SPI-1 effector proteins via regulating the transcription of the SicA/InvF genes, and the transportation of the effector protein SipC. In summary, licoflavonol, a novel natural inhibitor of Salmonella T3SS, could be a promising candidate for novel type of anti-virulence drugs.

[Diagnostic value of hepatobiliary phase imaging with GD-EOB-DTPA for hepatocellular carcinomas in cirrhosis].

OBJECTIVE: To assess the diagnostic value of hepatobiliary phase imaging with GD-EOB-DTPA for hepatocellular carcinomas (HCC) in cirrhosis. METHODS: A total of 43 cirrhotic patients with 45 HCC lesions underwent the examinations of T2WI, DWI, T1WI in-phase and opposed-phase and dynamic contrast enhancement and hepatobiliary phase. Two separate analyses of imaging set with and without hepatobiliary phase images were performed. The confidence scores for HCC diagnosis, consistency, area under the receiver operating characteristic (ROC) curve and sensitivity and positive predictive values of two observers were compared. RESULTS: After adding hepatobiliary phase, there was a significant increase of confidence scores in diagnosing HCC by both observers (P < 0.05) and the consistency of two observers also increased. The area under the ROC curve improved by both observers, but no significant differences were detected (P > 0.05). The sensitivity increased significantly (P < 0.05) and no significant differences were observed for the positive predictive values by both observers (P > 0.05). CONCLUSION: Hepatobiliary phase imaging may improve the diagnostic confidence and sensitivity of GD-EOB-DTPA for HCC in cirrhosis.

Diagnosis and management of acute complications in patients with colon cancer: bleeding, obstruction, and perforation.

Among the colorectal cancers, the incidence of colon cancer has obviously increased. As a result, the actual incidence of colon cancer has exceeded that of rectal cancer, which dramatically changed the long-existing epidemiological profile. The acute complications of colon cancer include bleeding, obstruction, and perforation, which were among the common acute abdominal surgical conditions. The rapid and accurate diagnosis of these acute complications was very important, and laparoscopic techniques can be applied in abdominal surgery for management of the complications.

Effects of charge state of nano-chitin on the properties of polyvinyl alcohol composite hydrogel.

The present work investigates the effects of nano-chitin with different charge, obtained by acid hydrolysis and TEMPO oxidation, on the structure and properties of borax crosslinked polyvinyl alcohol (PVA) hydrogels. In detail, nano-chitin prepared by acid hydrolysis (ACh) is positively charged (+28.8 mV). The electrostatic attraction between ACh and borax ions leads to a maximum tensile stress of composite hydrogel (ACh/PB), 54.25 KPa, 17 times of the borax crosslinked PVA (PB). In contrast, nano-chitin prepared by TEMPO-oxidation (TCh) shows negative charge (-59.0 mV). Due to the electrostatic repulsion with borax ions, the maximum tensile stress of composite hydrogel (TCh/PB) is only 9.25 KPa, a very limit reinforcing effect. However, TCh/PB showed better self-healing efficiency (96.0 %) as well as ionic conductivity (1.25 × 10-5 S/m). The present work shows that the charge state of the nano-chitin exerts great influence on the interaction with the crosslinking agent borax, therefore, affects the structure and properties of the final PVA composite hydrogels. The results could provide important information about making full use of nano-chitin as a reinforcement by adjusting its surface charge state.