Salicylic acid functionalized chitosan nanocomposite increases bioactive components and insect resistance of Agastache rugosa.

The abundance of monoterpenoids and phenolic compounds determines the medicinal quality and anti-insect properties of Agastache rugosa, which can be compromised by biotic stress such as herbivore attacks. The traditional use of chemical pesticides to mitigate herbivore interference is increasingly incompatible with sustainable agriculture. In response, nanotechnology-based biostimulants, which can activate metabolic processes to enhance plant growth and stress resistance, offer a more cost-effective and environmentally-friendly alternative. However, to date, it remains unknown how nano-biostimulants improve the therapeutic value and insect resistance of medicinal plants simultaneously. This study investigates the effect of 0-1000 mg/L of a nano-biostimulant salicylic acid functionalized chitosan nanocomposite (SCN) on the pharmacological and anti-herbivore properties of medicinal plant A. rugosa. Results showed that 100 mg/L SCN significantly inhibited Spodoptera litura growth by 62.9 %, and increased plant shoot and root biomass by 107.2 % and 77.6 %, respectively. Moreover, 100 mg/L SCN significantly upregulated the expression of the key genes (e.g., LS, L3OH, and CHS) involved in monoterpene and phenolic compounds biosynthesis by 1.4-10.1 folds, thus boosting the production of active compounds such as pulegone, ß-myrcene, and chlorogenic acid by 1.5-24.4 folds. These enhancements were superior to salicylic acid or chitosan alone. Altogether, our findings promote the sustainable and eco-friendly application of nano-biostimulant in improving the quality of medicinal plants and green pest control in agroecosystems.

Overexpression of PsMYB62 from Potentilla sericea confers cadmium tolerance in tobacco.

Excessive cadmium (Cd) content in soil poses serious hazard to the survival and development of various organisms. Potentilla sericea, characterized by strong resistance and high utility value, is an excellent choice for urban ecological greening. Plant MYB transcription factors can participate in respondind to a variety of abiotic stresses such as heavy metals and salinity. In this study, PsMYB62 was transformed into tobacco by leaf disc infestation to obtain PsMYB62 overexpressing tobacco lines, and its mechanism in response to Cd stress was further investigated. The results showed that with Cd treatment, PsMYB62 overexpressing tobacco exhibited significantly higher net photosynthetic rate, stomatal conductance, transpiration rate, intercellular CO2 concentration, chlorophyll content, as well as enhanced activities of superoxide dismutase, peroxidase, catalase, and glutathione reductase enzymes, along with increased levels of reduced glutathione, proline, and soluble protein compared to the control. Conversely, levels of O2- and H2O2, and malondialdehyde were markedly lower than those in the control(P<0.05). Moreover, the aboveground Cd content was notably higher in the control than in the transgenic lines, whereas the control was much lower than the transgenic lines in the belowground fraction, with Cd subcellular distribution ratios ranking as follows: cell wall fraction > soluble fraction > organelle fraction (P<0.05). The expression of NtHMA3, NtYSL, NtPDR4 and NtPDR5B were much lower in transgenic lines compared to the control, while NtNAS3, NtSOD, and NtGSH2 exhibited significantly higher expression. Consequently, this study provides genetic resources for molecular breeding of Cd-tolerant plants through genetic engineering and lays a theoretical foundation for the remediation of heavy metal-contaminated soil.

Bay-117082 treats sepsis by inhibiting neutrophil extracellular traps (NETs) formation through down-regulating NLRP3/N-GSDMD.

During the inflammatory storm of sepsis, a significant quantity of neutrophil extracellular traps (NETs) are generated, which act as a double-edged sword and not only impede the invasion of foreign microorganisms but also exacerbate organ damage. This study provides evidence that NETs can cause damage to alveolar epithelial cells in vitro. The sepsis model developed in this study showed a significant increase in NETs in the bronchoalveolar lavage fluid (BALF). The development of NETs has been shown to increase the lung inflammatory response and aggravate injury to alveolar epithelial cells. Bay-117082, a well-known NF-κB suppressor, is used to modulate inflammation. This analysis revealed that Bay-117082 efficiently reduced total protein concentration, myeloperoxidase activity, and inflammatory cytokines in BALF. Moreover, Bay-117082 inhibited the formation of NETs, which in turn prevented the activation of the pore-forming protein gasdermin D (GSDMD). In summary, these results indicated that excessive NET production during sepsis exacerbated the onset and progression of acute lung injury (ALI). Therefore, Bay-117082 could serve as a novel therapeutic approach for ameliorating sepsis-associated ALI.

A phase 1 proof-of-concept study evaluating safety, tolerability, and biological marker responses with combination therapy of CTLA4-Ig and interleukin-2 in amyotrophic lateral sclerosis.

Objective: To determine whether a combination therapy with abatacept (CTLA4-Ig) and interleukin-2 (IL-2) is safe and suppresses markers of oxidative stress, inflammation, and degeneration in ALS. Methods: In this open-label study, four participants with ALS received subcutaneous injections of low dose IL-2 (1 × 106 IU/injection/day) for 5 consecutive days every 2 weeks and one subcutaneous injection of CTLA4-Ig (125 mg/mL/injection) every 2 weeks coinciding with the first IL-2 injection of each treatment cycle. Participants received a total of 24 treatment cycles during the first 48 weeks in this 56-week study. They were closely monitored for treatment-emergent adverse events (TEAEs) and disease progression with the ALSFRS-R. Phenotypic changes within T cell populations and serum biological markers of oxidative stress [4-hydroxynonenal (4-HNE) and oxidized-LDL (ox-LDL)], inflammation (IL-18), and structural neuronal degeneration [neurofilament light chain (Nf-L)] were assessed longitudinally. Results: CTLA4-Ig/IL-2 therapy was safe and well-tolerated in all four participants over the 56-week study. During the first 24 weeks, the average rate of change in the ALSFRS-R was +0.04 points/month. Over the 48-week treatment period, the average rate of change was -0.13 points/month with one participant improving by 0.9 points/month while the other three participants experienced an average decrease of -0.47 points/month, which is slower than the average - 1.1 points/month prior to initiation of therapy. Treg suppressive function and numbers increased during treatment. Responses in the biological markers during the first 16 weeks coincided with minimal clinical progression. Mean levels of 4-HNE decreased by 30%, ox-LDL decreased by 19%, IL-18 decreased by 23%, and Nf-L remained the same, on average, in all four participants. Oxidized-LDL levels decreased in all four participants, 4-HNE and IL-18 levels decreased in three out of four participants, and Nf-L decreased in two out of four participants. Conclusion: The combination therapy of CTLA4-Ig and IL-2 in ALS is safe and well-tolerated with promising results of clinical efficacy and suppression of biomarkers of oxidative stress, neuroinflammation and neuronal degeneration. In this open-label study, the efficacy as measured by the ALSFRS-R and corresponding biomarkers suggests the therapeutic potential of this treatment and warrants further study in a phase 2 double-blind, placebo-controlled trial. Clinical trial registration: ClinicalTrials.gov, NCT06307301.

Synergistic analysis of lignin degrading bacterial consortium and its application in rice straw fiber film.

Fiber film have received widespread attention due to its green friendliness. We can use microorganisms to degrade lignin in straw to obtain cellulose and make fiber films. Herein, a group of high-temperature (50 °C) lignin degrading bacterial consortium (LDH) was enriched and culture conditions for lignin degradation were optimized. Combined with high-throughput sequencing technology, the synergistic effect of LDH-composited bacteria was analyzed. Then LDH was used to treat rice straw for the bio-pulping experiment. The results showed that the lignin of rice straw was degraded 32.4 % by LDH at 50 °C for 10 d, and after the optimization of culture conditions, lignin degradation rate increased by 9.05 % (P < 0.001). The bacteria that compose in LDH can synergistically degrade lignin. Paenibacillus can encode all lignin-degrading enzymes present in the LDH. Preliminary tests of LDH in the pulping industry have been completed. This study is the first to use high temperature lignin degrading bacteria to fabricate fiber film.

Synergistic effect of two bacterial strains promoting anaerobic digestion of rice straw to produce methane.

A large amount of agricultural waste causes global environmental pollution. Biogas production by microbial pretreatment is an important way to utilize agricultural waste resources. In this study, Sporocytophaga CG-1 (A, cellulolytic strain) was co-cultured with Bacillus clausii HP-1 (B, non-cellulolytic strain) to analyze the effect of pretreatment of rice straw on methanogenic capacity of anaerobic digestion (AD). The results showed that weight loss rate of filter paper of co-culture combination is 53.38%, which is 29.37% higher than that of A. The synergistic effect of B on A can promote its degradation of cellulose. The cumulative methane production rate of the co-culture combination was the highest (93.04 mL/g VS substrate), which was significantly higher than that of A, B and the control group (82.38, 67.28 and 67.70 mL/g VS substrate). Auxiliary bacteria can improve cellulose degradation rate by promoting secondary product metabolism. These results provide data support for the application of co-culture strategies in the field of anaerobic digestion practices.

Impacts of nano-acetamiprid pesticide on faba bean root metabolic response and soil health.

The associated benefits and potential environmental risks of nanopesticides on plant and soil health, particularly in comparison with traditional pesticides, have not been systematically elucidated. Herein, we investigated the impacts of the as-synthesized nano-acetamiprid (Nano-Ace, 20 nm) at low (10 mg/L), medium (50 mg/L), high (100 mg/L) doses and the corresponding high commercial acetamiprid (Ace, 100 mg/L) on the physiological and metabolic response of faba bean (Vicia faba L.) plants, as well as on rhizosphere bacterial communities and functions over short-, medium- and long-term exposures. Overall, Nano-Ace exposure contributed to basic metabolic pathways (e.g., flavonoids, amino acids, TCA cycle intermediate, etc.) in faba bean roots across the whole exposure period. Moreover, Nano-Ace exposure enriched rhizosphere beneficial bacteria (e.g., Streptomyces (420.7%), Pseudomonas (33.8%), Flavobacterium (23.3%)) and suppressed pathogenic bacteria (e.g., Acidovorax (44.5%)). Additionally, Nano-Ace exposure showed a trend of low promotion and high inhibition of soil enzyme activities (e.g., invertase, urease, arylsulfatase, alkaline phosphatase) involved in soil C, N, S, and P cycling, while the inhibition was generally weaker than that of conventional Ace. Altogether, this study indicated that the redox-responsive nano-acetamiprid pesticide possessed high safety for host plants and soil health.

Determining dense velocity fields for fluid images based on affine motion.

In this article, we address the problem of estimating fluid flows between two adjacent images containing fluid and non-fluid objects. Typically, traditional optical flow estimation methods lack accuracy, because of the highly deformable nature of fluid, the lack of definitive features, and the motion differences between fluid and non-fluid objects. Our approach captures fluid motions using an affine motion model for each small patch of an image. To obtain robust patch matches, we propose a best-buddies similarity-based method to address the lack of definitive features but many similar features in fluid phenomena. A dense set of affine motion models was then obtained by performing nearest-neighbor interpolation. Finally, dense fluid flow was recovered by applying the affine transformation to each patch and was improved by minimizing a variational energy function. Our method was validated using different types of fluid images. Experimental results show that the proposed method achieves the best performance.

Key Modulation of ROS and HSP for Effective Therapy Against Hypoxic Tumor with Multifunctional Nanosystem.

Background: Though nanomedicine-based photothermal therapy (PTT) has demonstrated promising prospect in tumor treatment due to its high therapeutic efficiency and controllable range, the overexpression of heat shock proteins (HSPs) during PTT can lead to intracellular thermal resistance and reduce its effectiveness. Reactive oxygen species (ROS), followed by the application of chemodynamic therapy (CDT) and photodynamic therapy (PDT), can eliminate HSPs and overcome thermal resistance. However, the tumor microenvironment, including hypoxia and glutathione (GSH) overexpression, impedes the production of ROS and therapeutic efficacy of CDT and PDT. Therefore, we proposed a multifunctional nanoplatform (HMPB@TCPP-Cu) driving PTT/ PDT/ CDT synergistic therapy for tumor treatment via modulating ROS and HSPs. Methods and Results: In this work, a novel nanoplatform (HMPB@TCPP-Cu) composed of O2/PTT supplier HMPB (hollow mesoporous Prussian blue) and the loaded PDT/CDT agent (TCPP-Cu2+) was prepared. HMPB acts as an photothermal converter, effectively raising the tumor temperature and inducing apoptosis. HMPB is also a potent catalase-like nanozyme, which can catalyze hydrogen peroxide into oxygen and reduce tumor hypoxia, thus elevating the efficiency of ROS production and the effectiveness of PDT with the wing of sonosensitizer-TCPP. The intracellular glutathione(GSH) was depleted by Cu2+ and •OH was generated along with the Cu2+/Cu+ converting and Cu+-mediated Fenton-like reaction. Subsequently, the increased levels of ROS effectively eliminate intratumoral thermal resistance. The HMPB@TCPP-Cu has achieved synergistic PTT/PDT/CDT for hepatoblastoma treatment and significant inhibition of tumor growth was detected both in vitro and in vivo. Conclusion: This study presents a multifunctional nanoplatform that combines photothermal/ chemodynamic/ photodynamic therapy for efficient hepatoblastoma treatment via modulating ROS and HSPs. Collectively, this study provides an appealing strategy in the cleavage of thermal resistance and a novel assistance and enhancement on thermal-related therapies.

The role of neutrophil extracellular traps in sepsis and sepsis-related acute lung injury.

Neutrophils release neutrophil extracellular traps (NETs) to trap pathogenic microorganisms. NETs are involved in the inflammatory response and bacterial killing and clearance. However, their excessive activation can lead to an inflammatory storm in the body, which may damage tissues and cause organ dysfunction. Organ dysfunction is the main pathophysiological cause of sepsis and also a cause of the high mortality rate in sepsis. Acute lung injury caused by sepsis accounts for the highest proportion of organ damage in sepsis. NET formation can lead to the development of sepsis because by promoting the release of interleukin-1 beta, interleukin-8, and tumor necrosis factor-alpha, thereby accelerating acute lung injury. In this review, we describe the critical role of NETs in sepsis-associated acute lung injury and review the current knowledge and novel therapeutic approaches.

Potentilla sericea stress-responsive spermine synthase PsSPMS enhances cadmium tolerance in Arabidopsis thaliana.

Potentilla sericea is resistant and tolerates rough management. It is an excellent garden groundcover for ecological restoration and soil consolidation for slope protection. Polyamines have functions such as promoting tissue growth and physiological resistance, while spermine synthase catalyzes the production of spermine. The PsSPMS gene from Potentilla sericea was cloned and transformed into Arabidopsis thaliana to study the response of transgenic Arabidopsis thaliana to cadmium stress. The results showed that the contents of spermidine, spermine as well as glutathione were higher in PsSPMS overexpressing Arabidopsis thaliana than the control, while the contents of putrescine were less than the control. Net photosynthetic rate, stomatal conductance, chlorophyll content, water use efficiency, electron transfer rate, PSII-related parameters, proline content, superoxide dismutase, and glutathione reductase activities were higher in PsSPMS overexpressing Arabidopsis thaliana than the control, while malondialdehyde, superoxide anion, and hydrogen peroxide contents were lower than the control. Correlation analysis showed significant differences between the indicators (P < 0.05 and P < 0.01). Expression of AtSPMS, AtSPD3, AtGSH2 and AtGR in transgenic Arabidopsis thaliana was higher than that of the control. Therefore, this study provides a genetic reference for the cultivation of cadmium-tolerant plants through genetic engineering and lays the foundation for further research on cadmium-tolerant Potentilla sericea.

SERS with Flexible ß-CD@AuNP/PTFE Substrates for In Situ Detection and Identification of PAH Residues on Fruit and Vegetable Surfaces Combined with Lightweight Network.

The detection of polycyclic aromatic hydrocarbons (PAHs) on fruit and vegetable surfaces is important for protecting human health and ensuring food safety. In this study, a method for the in situ detection and identification of PAH residues on fruit and vegetable surfaces was developed using surface-enhanced Raman spectroscopy (SERS) based on a flexible substrate and lightweight deep learning network. The flexible SERS substrate was fabricated by assembling ß-cyclodextrin-modified gold nanoparticles (ß-CD@AuNPs) on polytetrafluoroethylene (PTFE) film coated with perfluorinated liquid (ß-CD@AuNP/PTFE). The concentrations of benzo(a)pyrene (BaP), naphthalene (Nap), and pyrene (Pyr) residues on fruit and vegetable surfaces could be detected at 0.25, 0.5, and 0.25 µg/cm2, respectively, and all the relative standard deviations (RSD) were less than 10%, indicating that the ß-CD@AuNP/PTFE exhibited high sensitivity and stability. The lightweight network was then used to construct a classification model for identifying various PAH residues. ShuffleNet obtained the best results with accuracies of 100%, 96.61%, and 97.63% for the training, validation, and prediction datasets, respectively. The proposed method realised the in situ detection and identification of various PAH residues on fruit and vegetables with simplicity, celerity, and sensitivity, demonstrating great potential for the rapid, nondestructive analysis of surface contaminant residues in the food-safety field.

Multistage Anticoagulant Surfaces: A Synergistic Combination of Protein Resistance, Fibrinolysis, and Endothelialization.

Anticoagulant surface modification of blood-contacting materials has been shown to be effective in preventing thrombosis and reducing the dose of anticoagulant drugs that patients take. However, commercially available anticoagulant coatings, that is, both bioinert and bioactive coatings, are typically based on a single anticoagulation strategy. This puts the anticoagulation function of the coating at risk of failure during long-term use. Considering the several pathways of the human coagulation system, the synergy of multiple anticoagulation theories may provide separate, targeted effects at different stages of thrombosis. Based on this presumption, in this work, negatively charged poly(sodium p-styrenesulfonate-co-oligo(ethylene glycol) methyl ether methacrylate) and positively charged poly(lysine-co-1-adamantan-1-ylmethyl methacrylate) were synthesized to construct matrix layers on the substrate by electrostatic layer-by-layer self-assembly (LBL). Amino-functionalized ß-cyclodextrin (ß-CD-PEI) was subsequently immobilized on the surface by host-guest interactions, and heparin was grafted. By adjusting the content of poly(oligo(ethylene glycol) methyl ether methacrylate) (POEGMA), the interactions between modified surfaces and plasma proteins/cells were regulated. This multistage anticoagulant surface exhibits inertness at the initial stage of implantation, resisting nonspecific protein adsorption (POEGMA). When coagulation reactions occur, heparin exerts its active anticoagulant function in a timely manner, blocking the pathway of thrombosis. If thrombus formation is inevitable, lysine can play a fibrinolytic role in dissolving fibrin clots. Finally, during implantation, endothelial cells continue to adhere and proliferate on the surface, forming an endothelial layer, which meets the blood compatibility requirements. This method provides a new approach to construct a multistage anticoagulant surface for blood-contacting materials.

Biocompatible cationic polypeptoids with antibacterial selectivity depending on hydrophobic carbon chain length.

The overuse of antibiotics has triggered a new infection crisis and natural antimicrobial peptides (AMPs) have been extensively studied as an alternative to fight microorganisms. Polypeptoids, or polypeptide-biomimetics, offer similar properties to polypeptides and a highly tunable structure that has been synthesized by various methods such as ring opening polymerization (ROP) using N-carboxyanhydride monomers. Simultaneous high antibacterial activity and biocompatibility of a structure by efficient synthesis is desired in the application of those materials. Herein, a series of cationic polypeptoids (PNBs) with variable side chain lengths was obtained by introducing positive charges to the main chain in one step and preserving the backbone structure, namely polypeptoids (PNBM, PNBE, PNBB) with different end groups (methyl (M), ethyl (E), butyl (B)). To address the issue of infection in interventional biomedical implants, we report cost-effective modified polyurethane (PU) films (PU-PNBM, PU-PNBE, PU-PNBB) as physical-biological synergistic antibacterial surfaces that overcome problems such as steric hindrance and the solubility of the materials. Antibacterial selectivity was achieved by regulating the different side chain lengths. When methyl and ethyl were used as hydrophobic side chains, they can only selectively kill Gram-positive Staphylococcus aureus. PNBB, the most hydrophobic and with a butyl side chain can kill both Gram-negative Escherichia coli and Gram-positive Staphylococcus aureus and inhibit the growth of bacterial biofilms. Effective in both solution and modified substrate, its biocompatibility is not compromised while the antibacterial properties are substantially improved. Furthermore, PU-PNBB films demonstrated their potential in vivo antimicrobial efficiency in a model of S. aureus infection established on mouse skin. The synthesis route and the surface modification strategies are convenient, providing a solution to the problem of poor biocompatibility in antimicrobial surface applications and a strategy for the use of peptide polymers for targeted therapy after specific infections in the biomedical field.

Surface-enhanced Raman spectroscopy charged probes under inverted superhydrophobic platform for detection of agricultural chemicals residues in rice combined with lightweight deep learning network.

In this study, surface-enhanced Raman spectroscopy (SERS) charged probes and an inverted superhydrophobic platform were used to develop a detection method for agricultural chemicals residues (ACRs) in rice combined with lightweight deep learning network. First, positively and negatively charged probes were prepared to adsorb ACRs molecules to SERS substrate. An inverted superhydrophobic platform was prepared to alleviate the coffee ring effect and induce tight self-assembly of nanoparticles for high sensitivity. Chlormequat chloride of 15.5-0.05 mg/L and acephate of 100.2-0.2 mg/L in rice were measured with the relative standard deviation of 4.15% and 6.25%. SqueezeNet were used to develop regression models for the analysis of chlormequat chloride and acephate. And the excellent performances were obtained with the coefficients of determination of prediction of 0.9836 and 0.9826 and root-mean-square errors of prediction of 0.49 and 4.08. Therefore, the proposed method can realize sensitive and accurate detection of ACRs in rice.

Detection of apple fruit damages through Raman spectroscopy with cascade forest.

Apple fruit damages seriously cause product and economic losses, infringe consumer rights and interests, and have harmful effects on human and livestock health. In this study, Raman spectroscopy (RS) and cascade forest (CForest) were adopted to determine apple fruit damages. First, the RS spectra of healthy, bruised, Rhizopus-infected, and Botrytis-infected apples were measured. Spectral changes and band attribution were analyzed. Different modeling methods were combined with various pre-processing and dimension reduction methods to construct recognition models. Among all models, CForest constructed with full spectra processed by Savitsky-Golay smoothing obtained the best performance with accuracies of 100%, 91.96%, and 92.80% in the training, validation, and test sets (ACCTE). And the modeling time is reduced to 1/3 of the full-spectra model with a similar ACCTE of 91.56% after principal component analysis. Overall, RS and CForest provided a non-destructive, rapid, and accurate identification of apple fruit damages and could be used in disease recognition and safety assurance of other fruits.

Changes of Plasma Blood Ammonia Levels of Chinese Healthy People and the Establishment of Reference Intervals.

BACKGROUND: Blood ammonia detection is used for the diagnosis or differential diagnosis of various hepatitis virus infections, severe liver cirrhosis, and hepatic encephalopathy. It is also one of the important indexes reflecting liver coma, Reyes syndrome, and other diseases. However, blood ammonia changes rapidly with time. If samples are not sent and detected in time, the results will be wrong, resulting in clinical misdiagnosis and life danger to patients. The purpose of this paper is to explore the change of blood ammonia with time and establish its reference interval. METHODS: For this study, 228 healthy patients (111 males and 117 females) were selected who underwent physical examination at the Health Management Center of the Second Xiangya Hospital of Central South University from April to May 2021. The blood ammonia detection kit (colorimetric method) produced by Roche Diagnostics GmbH of Germany was used for detection on the Roche cobas c702 automatic biochemical analyzer. After eliminating outliers from the obtained test results, they were grouped according to gender and age, and SPSS 26.0 software was employed to statistically analyze the blood ammonia test results. RESULTS: The differences in blood ammonia levels at each detection time were statistically significant (p < 0.05). The differences in blood ammonia levels between male and female subjects at 1 hour, 2 hours, and 3 hours were statistically significant (p < 0.05), but all ages saw no statistically significant difference in blood ammonia levels between segments (p > 0.05). The blood ammonia levels of each detection time and different genders showed a normal distribution. Therefore, it is necessary to take the 95% (X ± 1.96S) results of both sides as the reference interval according to the detection time and gender, and establish the reference intervals. The 1-hour blood ammonia reference interval for healthy men in Changsha is 15.8 - 47.5 µmol/L, for healthy women it is 12.4 - 39.6 µmol/L; the 2-hour blood ammonia reference interval for healthy men is 22.3 - 56.5 µmol/L, and for healthy women it is 19.1 - 48.0 µmol/L; the reference interval of 3-hours blood ammonia for healthy men is 27.9 - 65.7 µmol/L, and for healthy women it is 24.6 - 56.7 µmol/L. CONCLUSIONS: There are differences in blood ammonia levels between men and women at different detection times in Changsha. A reference interval suitable for blood ammonia in healthy individuals in the region should be established according to the detection time and gender, so as to provide better relevant evidence for clinical diagnosis.

Detection of amylase activity and moisture content in rice by reflectance spectroscopy combined with spectral data transformation.

In this study, reflectance spectroscopy was used to achieve rapid and non-destructive detection of amylase activity and moisture content in rice. Since rice husk can interfere with spectral measurements, spectral data transformation was used to remove the husk interference. Reflectance spectra of rice were transformed by direct standardization, convolutional autoencoder network, and kernel regression (KR). Then, random frog and elliptical envelope were adopted to select effective wavelengths, and partial least squares regression (PLSR) and support vector regression were used to establish analysis models. The optimal transformation was from KR, and PLSR and effective wavelengths of the transformed spectra obtained excellent performance with coefficient of determination of test of 0.6987 and 0.8317 and root-mean-square error of test of 0.3359 and 2.2239, respectively. The result was better than that of the rice spectra and was close to that of the husked rice spectra. When the moisture content was integrated into the regression model of amylase activity, a better result was obtained. Thus, the proposed method can detect amylase activity and moisture content in rice accurately.

Titin-truncating variants in hiPSC cardiomyocytes induce pathogenic proteinopathy and sarcomere defects with preserved core contractile machinery.

Titin-truncating variants (TTNtv) are the single largest genetic cause of dilated cardiomyopathy (DCM). In this study we modeled disease phenotypes of A-band TTNtv-induced DCM in human induced pluripotent stem cell-derived cardiomyocytes (hiPSC-CMs) using genome editing and tissue engineering technologies. Transcriptomic, cellular, and micro-tissue studies revealed that A-band TTNtv hiPSC-CMs exhibit pathogenic proteinopathy, sarcomere defects, aberrant Na+ channel activities, and contractile dysfunction. These phenotypes establish a dual mechanism of poison peptide effect and haploinsufficiency that collectively contribute to DCM pathogenesis. However, TTNtv cellular defects did not interfere with the function of the core contractile machinery, the actin-myosin-troponin-Ca2+ complex, and preserved the therapeutic mechanism of sarcomere modulators. Treatment of TTNtv cardiac micro-tissues with investigational sarcomere modulators augmented contractility and resulted in sustained transcriptomic changes that promote reversal of DCM disease signatures. Together, our findings elucidate the underlying pathogenic mechanisms of A-band TTNtv-induced DCM and demonstrate the validity of sarcomere modulators as potential therapeutics.

Distinct Mechanisms for Increased Cardiac Contraction Through Selective Alteration of Either Myosin or Troponin Activity.

Modulation of sarcomere contractility represents a new therapeutic opportunity for the treatment of heart failure by directly targeting the thick and thin filament proteins of the sarcomere to increase cardiac muscle contraction. This study compared the effect of 2 small molecules (M and T) that selectively alter myosin thick filament (M) or troponin thin filament (T) activity on overall cardiac muscle mechanics. This study revealed key differences related to the mechanism utilized by M and T to increase contractile force generation and suggests that targeting different proteins within the sarcomere may result in differentiating therapeutic profiles.