A review of advancements in chitosan-essential oil composite films: Better and sustainable food preservation with biodegradable packaging.

In response to the environmental pollution caused by non-degradable and non-recyclable plastic packaging films (PPFs) and the resulting health concerns due to the migration of microplastics into food, the development of biodegradable food packaging films has gained great attention. Chitosan has been extensively utilized in the food industry owing to its abundant availability, exceptional biocompatibility, degradability, and antimicrobial properties. Chitosan-essential oil composite films (CEOs) represent a promising avenue to replace conventional PPFs. This review provides an overview of the advancements in CEOs over the past decade, focusing on the effects of essential oils (EOs) on CEOs in terms of antimicrobial activity, antioxidant effect, gas barrier, light barrier, and mechanical properties. It also offers insights into the controlled release of EOs in CEOs and summarizes the application of CEOs in fresh food preservation.

Structural Optimization of Marine Natural Product Pretrichodermamide B for the Treatment of Colon Cancer by Targeting the JAK/STAT3 Signaling Pathway.

Marine natural product (MNP) pretrichodermamide B (Pre B, 9) was identified as a novel STAT3 inhibitor in our previous work, while its metabolic instability hindered its further development. To address this drawback, ligand structure-based drug design was adopted leading to a series of Pre B derivatives. Among them, MNP trichodermamide B (tri B, 24) obtained by skeletal rearrangement exhibited more potent antiproliferative activity with an IC50 value of 0.12 µM against HCT116. Notably, 24 stood out with improved metabolic stability (T1/2 = 31 min) and more favorable oral bioavailability (F = 37.5%). Further studies indicated that 24 blocked JAK/STAT3 signaling in dose- and time-dependent manner. In vivo, 24 suppressed tumor growth (TGI = 65%) at a dose of 20 mg/kg in a HCT116-derived xenograft mouse model. Overall, 24 might be a promising lead compound for colon cancer and is worthy of further investigation.

Magnetic properties of CrMnGen (n = 3-20) clusters.

Due to the potential applications in next-generation micro/nano electronic devices and functional materials, magnetic germanium (Ge)-based clusters are receiving increasing attention. In this work, we reported the structures, electronic and magnetic properties of CrMnGen with sizes n = 3-20. Transition metals (TMs) of Cr and Mn tend to stay together and be surrounded by Ge atoms. Small sized clusters with n ≤ 8 prefer to adopt bipyramid-based structures as the motifs with the excess Ge atoms absorbed on the surface. Starting from n = 9, the structure with one TM atom interior appears and persists until n = 16, and for larger sizes n = 17-20, the two TM atoms are full-encapsulated by Ge atoms to form endohedral structures. The Hirshfeld population analyses show that Cr atom always acts as the electron donor, while Mn atom is always the acceptor except for sizes 3 and 6. The average binding energies of these clusters increase with cluster size n, sharing a very similar trend as that of CrMnSin (n = 4-20) clusters, which indicates that it is favorable to form large-sized clusters. CrMnGen (n = 6, 13, 16, 19, and 20) clusters prefer to exhibit ferromagnetic Cr-Mn coupling, while the remaining clusters are ferrimagnetic.

Data-Driven Robust Finite-Iteration Learning Control for MIMO Nonrepetitive Uncertain Systems.

This work considers three main problems related to fast finite-iteration convergence (FIC), nonrepetitive uncertainty, and data-driven design. A data-driven robust finite-iteration learning control (DDRFILC) is proposed for a multiple-input-multiple-output (MIMO) nonrepetitive uncertain system. The proposed learning control has a tunable learning gain computed through the solution of a set of linear matrix inequalities (LMIs). It warrants a bounded convergence within the predesignated finite iterations. In the proposed DDRFILC, not only can the tracking error bound be determined in advance but also the convergence iteration number can be designated beforehand. To deal with nonrepetitive uncertainty, the MIMO uncertain system is reformulated as an iterative incremental linear model by defining a pseudo partitioned Jacobian matrix (PPJM), which is estimated iteratively by using a projection algorithm. Further, both the PPJM estimation and its estimation error bound are included in the LMIs to restrain their effects on the control performance. The proposed DDRFILC can guarantee both the iterative asymptotic convergence with increasing iterations and the FIC within the prespecified iteration number. Simulation results verify the proposed algorithm.

Antiferromagnetic Chromium-Doped Tin Clusters.

The trend toward further miniaturization of micronano antiferromagnetic (AFM) spintronic devices has led to a strong demand for low-dimensional materials. The assembly of AFM clusters to produce such materials is a potential pathway that promotes studies on such clusters. In this work, we report on the discovery of the AFM Cr2Snx (x = 3-20) clusters with a stepwise growth at the density functional theory (DFT) level. In comparison, the two Cr atoms tend to stay together and be buried by Sn atoms, forming endohedral structures with one Cr atom encapsulated at size 9 and finally forming a full-encapsulated structure at size 17. Each successive cluster size is composed of its predecessor with an extra Sn atom adsorbed onto the face, giving evidence of stepwise growth. All these Cr2Snx (x = 3-20) clusters are antiferromagnets, except for the triplet-state ferrimagnetic Cr2Sn11, and all their singly negatively and positively charged ions are ferromagnets. The found stable Cr2Sn17 cluster can dimerize, yielding dimers and trimers without noticeably distorting the geometrical structure and magnetic properties of each of its constituent cluster monomers, making it possible as a building block for AFM materials.

Extending the Grading of Recommendations Assessment, Development and Evaluation (GRADE) in Traditional Chinese Medicine (TCM): The GRADE-TCM.

AIM: To extend and form the "Grading of Recommendations Assessment, Development and Evaluation in Traditional Chinese Medicine" (GRADE-TCM). METHODS: Methodologies were systematically reviewed and analyzed concerning evidence-based TCM guidelines worldwide. A survey questionnaire was developed based on the literature review and open-end expert interviews. Then, we performed expert consensus, discussion meeting, opinion collection, external examination, and the GRADE-TCM was formed eventually. RESULTS: 265 Chinese and English TCM guidelines were included and analyzed. Five experts completed the open-end interviews. Ten methodological entries were summarized, screened and selected. One round of consensus was conducted, including a total of 22 experts and 220 valid questionnaire entries, concerning 1) selection of the GRADE, 2) GRADE-TCM upgrading criteria, 3) GRADE-TCM evaluation standard, 4) principles of consensus and recommendation, and 5) presentation of the GRADE-TCM and recommendation. Finally, consensus was reached on the above 10 entries, and the results were of high importance (with voting percentages ranging from 50 % to 81.82 % for "very important" rating) and strong reliability (with the Cr ranging from 0.93 to 0.99). Expert discussion meeting (with 40 experts), opinion collection (in two online platforms) and external examination (with 14 third-party experts) were conducted, and the GRADE-TCM was established eventually. CONCLUSION: GRADE-TCM provides a new extended evidence-based evaluation standard for TCM guidelines. In GRADE-TCM, international evidence-based norms, characteristics of TCM intervention, and inheritance of TCM culture were combined organically and followed. This is helpful for localization of the GRADE in TCM and internationalization of TCM guidelines.

Metal-Phenolic Networks-Reinforced Extracellular Matrix Scaffold for Bone Regeneration via Combining Radical-Scavenging and Photo-Responsive Regulation of Microenvironment.

The limited regulation strategies of the regeneration microenvironment significantly hinder bone defect repair effectiveness. One potential solution is using biomaterials capable of releasing bioactive ions and biomolecules. However, most existing biomaterials lack real-time control features, failing to meet high regulation requirements. Herein, a new Strontium (Sr) and epigallocatechin-3-gallate (EGCG) based metal-phenolic network with polydopamine (PMPNs) modification is prepared. This material reinforces a biomimetic scaffold made of extracellular matrix (ECM) and hydroxyapatite nanowires (nHAW). The PMPNs@ECM/nHAW scaffold demonstrates exceptional scavenging of free radicals and reactive oxygen species (ROS), promoting HUVECs cell migration and angiogenesis, inducing stem cell osteogenic differentiation, and displaying high biocompatibility. Additionally, the PMPNs exhibit excellent photothermal properties, further enhancing the scaffold's bioactivities. In vivo studies confirm that PMPNs@ECM/nHAW with near-infrared (NIR) stimulation significantly promotes angiogenesis and osteogenesis, effectively regulating the microenvironment and facilitating bone tissue repair. This research not only provides a biomimetic scaffold for bone regeneration but also introduces a novel strategy for designing advanced biomaterials. The combination of real-time photothermal intervention and long-term chemical intervention, achieved through the release of bioactive molecules/ions, represents a promising direction for future biomaterial development.

Rehabilitation exercise-driven symbiotic electrical stimulation system accelerating bone regeneration.

Electrical stimulation can effectively accelerate bone healing. However, the substantial size and weight of electrical stimulation devices result in reduced patient benefits and compliance. It remains a challenge to establish a flexible and lightweight implantable microelectronic stimulator for bone regeneration. Here, we use self-powered technology to develop an electric pulse stimulator without circuits and batteries, which removes the problems of weight, volume, and necessary rigid packaging. The fully implantable bone defect electrical stimulation (BD-ES) system combines a hybrid tribo/piezoelectric nanogenerator to provide biphasic electric pulses in response to rehabilitation exercise with a conductive bioactive hydrogel. BD-ES can enhance multiple osteogenesis-related biological processes, including calcium ion import and osteogenic differentiation. In a rat model of critical-sized femoral defects, the bone defect was reversed by electrical stimulation therapy with BD-ES and subsequent bone mineralization, and the femur completely healed within 6 weeks. This work is expected to advance the development of symbiotic electrical stimulation therapy devices without batteries and circuits.

Determination of Ground State Structures of Snx - (x=21-35) Clusters.

In this work, an unbiased global search with a homemade genetic algorithm was performed to investigate the structural evolution and electronic properties of Snx - (x=21-35) clusters with density functional theory (DFT) calculations. All the ground-state structures for all these Snx - (x=21-35) clusters have been confirmed by the comparison of the experimental and simulated photoelectron spectra (PESs). It has been revealed that all Snx - (x=21-35) clusters are tricapped trigonal prism (TTP)-based structures consisting of two (for sizes x=21-28) or three (for x=29-35) TTP units, with the remaining atoms adsorbed on the surface or inserted between TTP units. The gradually decreasing HOMO-LUMO gaps indicate that these clusters are undergoing semiconductor-to-metal transformation. The average binding energies show that the structural stabilities of Snx - clusters are not as good as that of silicon and germanium clusters. It found that sizes x=23, 25, 29, 33 show high relative stability.

Roles of temperature and ventilation in oxygen consumption: A chemical kinetics view from the van't Hoff-based formulation.

In this study, we successfully estimated the apparent activation energy of a microbially driven oxygen-consuming reaction (microbial-driven) based on tracer data. The concept of the apparent chemical reaction rate constant was employed to estimate various thermodynamic parameters associated with the oxygen consumption rate in conjunction with Arrhenius/Eyring equations. Normal Ea values of 80-90 kJ mol-1 were found in the upper layers of the South China Sea and Sulu Sea, while higher Ea values (300-1000 kJ mol-1) were observed in the rapidly ventilated Mediterranean Sea, the Sea of Japan, and the Bering Sea with lower temperatures. We classified the characteristics of typical sea basins into four categories. The temperature-dependent oxygen consumption rate relationship in each marine region was systematically calculated to derive the respective thermodynamic characteristic values. This allowed us to parameterize the rate-temperature relationship into thermodynamic quantities, enabling more effective integration of distinct basin characteristics within different sea areas into the marine biochemical model. Parameterization facilitates relatively accurate prediction of changes such as temperature, oxygen consumption rate.

Effects of Twin-Block with an expanding device on the upper airway in growing children with skeletal class II malocclusion-a retrospective study based on the consistency of three-dimensional and two-dimensional data.

OBJECTIVES: Skeletal class II malocclusion is one of the most common malocclusions. Among the functional appliances for skeletal class II malocclusion, the Twin-Block appliance with a maxillary expander is effective in repositioning the mandible forward. In this study, we focused our efforts on investigating the effects of Twin-Block appliances with maxillary expanders on the upper airway in growing children with skeletal class II malocclusion by tracing and measuring lateral cephalograms after evaluating the consistency of three-dimensional CBCT data and two-dimensional lateral cephalogram data. MATERIALS AND METHODS: A total of 102 patients ranging from 9 to 15 years old (11.37 ± 2.80, male/female ratio = 1:1) with skeletal class II malocclusion were selected to evaluate the consistency of CBCT data and lateral cephalogram data. The strongly and moderately correlated segments were then selected to study the effects of Twin-Block with a maxillary expander on the upper airway in 66 growing children with skeletal class II malocclusion (11.31 ± 1.23 years old, male/female ratio = 1:1) by lateral cephalograms. RESULTS: The results showed a strong significant correlation in the nasopharynx (r = 0.708) and moderate significant correlations in the overall upper airway (r = 0.641), palatopharynx (r = 0.553), and glossopharynx (r = 0.575) but a weak correlation in the hypopharynx (r = 0.323). The corresponding determination coefficient (R2) was also determined by scatter plot analysis. Moreover, compared with the pretreatment data (T1), the total area of the upper airway and the areas of the nasopharynx, palatopharynx, and glossopharynx after functional treatment (T2) increased statistically and significantly. CONCLUSIONS: Lateral cephalograms can reflect the volume of the nasopharynx and oropharynx in skeletal class II children to a certain extent, while Twin-Block appliances with maxillary expanders can widen the volume of the nasopharynx and oropharynx significantly. CLINICAL RELEVANCE: The lateral cephalogram is reliable for analyzing the nasopharynx, palatopharynx, and glossopharynx in orthodontic clinical practice. Twin-Block appliances with maxillary expanders have a positive effect on skeletal class II patients with airway stenosis.

Accessory navicular in children.

Accessory navicular (AN) is a developmental variation of the secondary ossification center of the navicular tuberosity. Ten percent of patients with AN will have pain symptoms that affect walking and life. As the AN changes the position of the posterior tibial tendon insertion, children with AN often have posterior tibial tendon function insufficiency and flexible flat foot. Surgical treatment is often required after failure of conservative treatment. This article reviewed the etiology, clinical manifestations, complications, and treatment methods of AN.

GLP-1 Receptor Agonist Improves Mitochondrial Energy Status and Attenuates Nephrotoxicity In Vivo and In Vitro.

High-sugar and high-fat diets cause significant harm to health, especially via metabolic diseases. In this study, the protective effects of the antidiabetic drug exenatide (synthetic exendin-4), a glucagon-like peptide 1 (GLP-1) receptor agonist, on high-fat and high-glucose (HFHG)-induced renal injuries were investigated in vivo and in vitro. In vivo and in vitro renal injury models were established. Metabolomic analysis based on 1H-nuclear magnetic resonance was performed to examine whether exenatide treatment exerts a protective effect against kidney injury in diabetic rats and to explore its potential molecular mechanism. In vivo, 8 weeks of exenatide treatment resulted in the regulation of most metabolites in the diabetes mellitus group. In vitro results showed that exendin-4 restored the mitochondrial functions of mesangial cells, which were perturbed by HFHG. The effects of exendin-4 included the improved antioxidant capacity of mesangial cells, increased the Bcl-2/Bax ratio, and reduced protein expression of cyt-c and caspase-3 activation. In addition, exendin-4 restored mesangial cell energy metabolism by increasing succinate dehydrogenase and phosphofructokinase activities and glucose consumption while inhibiting pyruvate dehydrogenase E1 activity. In conclusion, GLP-1 agonists improve renal injury in diabetic rats by ameliorating metabolic disorders. This mechanism could be partially related to mitochondrial functions and energy metabolism.

Chitosan-based edible film incorporated with wampee (Clausena lansium) seed essential oil: Preparation, characterization and biological activities.

Chitosan (Ch)-based edible composite films were prepared by incorporating blending wampee seed essential oil (WSEO) into a Ch matrix, using the incorporation ratio as a variable. The physical, mechanical properties, structure morphology and rheological properties were determined using tensile strength (TS), elongation at break (EB), water vapor permeability (WVP) tests together with Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM) observations and apparent viscosity and shear rate. In addition, the antimicrobial, antioxidant activities were investigated by the DPPH & ABTS radicals scavenging and inhibition zone assays, respectively. Compared with Ch, the incorporation of WSEO significantly decreased (P < 0.05) the TS, EB, and WVP values, especially when the WSEO ratio reached 1.0 % or higher. Meanwhile, the films exhibited greatly improved visible light barrier performance after WSEO incorporation. Both FTIR spectroscopy and SEM observations reflected the crosslinking between WSEO and Ch. Meanwhile, the composite films demonstrated smaller particle size and weaker rheological viscosities, which enhanced the antimicrobial and antioxidant capabilities when compared with those of Ch. Therefore, this study suggested that WSEO incorporated with Ch is an effective ingredient for the preparation of edible films with enhanced physicochemical and biological properties.

Educating the next generation of cancer researchers: Evaluation of a cancer research partnership training program.

African American, American Indian and Alaska Native, Hispanic (or Latinx), Native Hawaiian, and other Pacific Islander groups are underrepresented in the biomedical workforce, which is one of the barriers to addressing cancer disparities among minority populations. The creation of a more inclusive biomedical workforce dedicated to reducing the burden of cancer health disparities requires structured, mentored research and cancer-related research exposure during the earlier stages of training. The Summer Cancer Research Institute (SCRI) is a multicomponent 8-week intensive summer program funded under the Partnership between a Minority Serving Institute and a National Institutes of Health-designated Comprehensive Cancer Center. In this survey study, we found that students who participated in the SCRI Program reported greater knowledge and interest in pursuing careers in cancer-related fields than their counterparts who did not participate in SCRI. Successes, challenges, and solutions in providing training in cancer and cancer health disparities research to improve diversity in the biomedical fields were also discussed.

Flexible Fabrication and Hybridization of Bioactive Hydrogels with Robust Osteogenic Potency.

Osteogenic scaffolds reproducing the natural bone composition, structures, and properties have represented the possible frontier of artificially orthopedic implants with the great potential to revolutionize surgical strategies against the bone-related diseases. However, it is difficult to achieve an all-in-one formula with the simultaneous requirement of favorable biocompatibility, flexible adhesion, high mechanical strength, and osteogenic effects. Here in this work, an osteogenic hydrogel scaffold fabricated by inorganic-in-organic integration between amine-modified bioactive glass (ABG) nanoparticles and poly(ethylene glycol) succinimidyl glutarate-polyethyleneimine (TSG-PEI) network was introduced as an all-in-one tool to flexibly adhere onto the defective tissue and subsequently accelerate the bone formation. Since the N-hydroxysuccinimide (NHS)-ester of tetra-PEG-SG polymer could quickly react with the NH2-abundant polyethyleneimine (PEI) polymer and ABG moieties, the TSG-PEI@ABG hydrogel was rapidly formed with tailorable structures and properties. Relying on the dense integration between the TSG-PEI network and ABG moieties on a nano-scale level, this hydrogel expressed powerful adhesion to tissue as well as durable stability for the engineered scaffolds. Therefore, its self-endowed biocompatibility, high adhesive strength, compressive modulus, and osteogenic potency enabled the prominent capacities on modulation of bone marrow mesenchymal stem cell (BMSCs) proliferation and differentiation, which may propose a potential strategy on the simultaneous scaffold fixation and bone regeneration promotion for the tissue engineering fields.

A type I-F CRISPRi system unveils the novel role of CzcR in modulating multidrug resistance of Pseudomonas aeruginosa.

Pseudomonas aeruginosa has abundant signaling systems that exquisitely control its antibiotic resistance in response to different environmental cues. Understanding the regulation of antibiotic resistance will provide important implications for precise antimicrobial interventions. However, efficient genetic tools for functional gene characterizations are sometimes not available, particularly, in clinically isolated strains. Here, we established a type I-F CRISPRi (CSYi) system for programmable gene silencing. By incorporating anti-CRISPR proteins, this system was even applicable to bacterial hosts encoding a native type I-F CRISPR-Cas system. With the newly developed gene-silencing system, we revealed that the response regulator CzcR from the zinc (Zn2+)-responsive two-component system CzcS/CzcR is a repressor of efflux pumps MexAB-OprM and MexGHI-OpmD, which inhibits the expression of both operons by directly interacting with their promoters. Repression of MexAB-OprM consequently increases the susceptibility of P. aeruginosa to multiple antibiotics such as levofloxacin and amikacin. Together, this study provided a simple approach to study gene functions, which enabled us to unveil the novel role of CzcR in modulating efflux pump genes and multidrug resistance in P. aeruginosa. IMPORTANCE P. aeruginosa is a ubiquitous opportunistic pathogen frequently causing chronic infections. In addition to being an important model organism for antibiotic-resistant research, this species is also important for understanding and exploiting CRISPR-Cas systems. In this study, we established a gene-silencing system based on the most abundant type I-F CRISPR-Cas system in this species, which can be readily employed to achieve targeted gene repression in multiple bacterial species. Using this gene-silencing system, the physiological role of Zn2+ and its responsive regulator CzcR in modulating multidrug resistance was unveiled with great convenience. This study not only displayed a new framework to expand the abundant CRISPR-Cas and anti-CRISPR systems for functional gene characterizations but also provided new insights into the regulation of multidrug resistance in P. aeruginosa and important clues for precise anti-pseudomonal therapies.

Arteriolosclerosis CSVD: a common cause of dementia and stroke and its association with cognitive function and total MRI burden.

Objective: Arteriolosclerosis cerebral small vessel disease (CSVD) is a common type of CSVD. This study aimed to explore the factors associated with cognitive function and total MRI burden related to the disease. Methods: The demographic characteristics, clinical manifestations, cognitive function score, Barthel Index (BI), blood test index, and follow-up results of arteriolosclerosis CSVD patients treated for the first time in our hospital from January 2014 to August 2022 were collected. White matter hyperintensity (WMH) Fazekas score, total MRI burden, and cerebral atrophy grade were evaluated according to brain MRI findings. Factors associated with CSVD cognitive function were analyzed by binary logistic regression. The correlative factors related to the total MRI burden of CSVD were analyzed by ordered multiple logistic regression. Results: A total of 146 patients were included in this study, of which 132 cases (90.4%) had hypertension. There were 108 patients (74.0%) with cognitive dysfunction, 97 patients (66.4%) with balance and gait disorders, and 83 patients (56.8%) with moderate-to-severe dependence in daily life (BI ≤ 60 points). Of 146 patients, 79 (54.1%) completed clinical and imaging follow-ups for a median of 3 years. The number of patients with cognitive impairment and BI ≤ 60 points after follow-up significantly increased compared with the first admission (P < 0.001). There were also significant differences in total MRI burden (P = 0.001), WMH Fazekas score, and cerebral atrophy grade (P < 0.001). Mean age (P = 0.012), median deep WMH Fazekas score (P = 0.028), and median deep (P < 0.001) and superficial (P =0.002) cerebral atrophy grade of patients with cognitive impairment at first admission were all higher than those with non-cognitive impairment. Multivariate analysis showed that deep cerebral atrophy was independently and significantly associated with cognitive impairment of CSVD (P = 0.024), and hypertension was significantly and independently associated with total MRI burden (P = 0.001). Conclusion: The disease course of arteriolosclerosis CSVD may be related to cognitive function and total MRI burden. Deep cerebral atrophy was an independent risk factor for cognitive dysfunction in arteriolosclerosis CSVD, and hypertension was an independent risk factor for total MRI burden.

Structure-Based Design and Characterization of the Highly Potent and Selective Covalent Inhibitors Targeting the Lysine Methyltransferases G9a/GLP.

Protein lysine methyltransferases G9a and GLP, which catalyze mono- and di-methylation of histone H3K9 and nonhistone proteins, play important roles in diverse cellular processes. Overexpression or dysregulation of G9a and GLP has been identified in various types of cancer. Here, we report the discovery of a highly potent and selective covalent inhibitor 27 of G9a/GLP via the structure-based drug design approach following structure-activity relationship exploration and cellular potency optimization. Mass spectrometry assays and washout experiments confirmed its covalent inhibition mechanism. Compound 27 displayed improved potency in inhibiting the proliferation and colony formation of PANC-1 and MDA-MB-231 cell lines and exhibited enhanced potency in reducing the levels of H3K9me2 in cells compared to noncovalent inhibitor 26. In vivo, 27 showed significant antitumor efficacy in the PANC-1 xenograft model with good safety. These results clearly indicate that 27 is a highly potent and selective covalent inhibitor of G9a/GLP.