-
1.
Advances in peptide-based drug delivery systems.
Guo, S, Wang, J, Wang, Q, Wang, J, Qin, S, Li, W
Heliyon. 2024;(4):e26009
Abstract
Drug delivery systems (DDSs) are designed to deliver drugs to their specific targets to minimize their toxic effects and improve their susceptibility to clearance during targeted transport. Peptides have high affinity, low immunogenicity, simple amino acid composition, and adjustable molecular size; therefore, most peptides can be coupled to drugs via linkers to form peptide-drug conjugates (PDCs) and act as active pro-drugs. PDCs are widely thought to be promising DDSs, given their ability to improve drug bio-compatibility and physiological stability. Peptide-based DDSs are often used to deliver therapeutic substances such as anti-cancer drugs and nucleic acid-based drugs, which not only slow the degradation rate of drugs in vivo but also ensure the drug concentration at the targeted site and prolong the half-life of drugs in vivo. This article provides an profile of the advancements and future development in functional peptide-based DDSs both domestically and internationally in recent years, in the expectation of achieving targeted drug delivery incorporating functional peptides and taking full advantage of synergistic effects.
-
2.
Effect of Controlling Nb Content and Cooling Rate on the Microstructure, Precipitation Phases, and Mechanical Properties of Rebar.
Shen, B, Gu, S, Wang, J, Wei, F, Li, Z, Zeng, Z, Zhang, J, Li, C
Materials (Basel, Switzerland). 2024;(7)
Abstract
Seismic anti-seismic rebar, as materials for supporting structures in large buildings, need to have excellent mechanical properties. By increasing the Nb content and controlling the cooling rate, the microstructure and precipitation behavior of the steel are adjusted to develop seismic anti-seismic rebar with excellent mechanical properties. Scanning electron microscopy (SEM), electron backscatter diffraction (EBSD), transmission electron microscopy (TEM), and a universal tensile testing machine were used to characterize the microstructure, precipitation phases, and mechanical properties of the experimental steels. The results show that the ferrite grain size, pearlite lamellae layer (ILS), and small-angle grain boundaries (LAGB) content of the high-Nb steels decreased to 6.39 μm, 0.12 μm, and 48.7%, respectively, as the Nb content was increased from 0.017 to 0.023 wt.% and the cooling rate was increased from 1 to 3 °C·s-1. The strength of the {332}<113>α texture is the highest in the high-Nb steels. The precipitated phase is (Nb, Ti, V)C with a diameter of ~50 nm, distributed on ferrite, and the matrix/precipitated phase mismatch is 8.16%, forming a semicommon-lattice interface between the two. The carbon diffusion coefficient model shows that increasing the Nb content can inhibit the diffusion of carbon atoms and reduce the ILS. The yield strength of the high-Nb steel is 556 MPa, and the tensile strength is 764 MPa.
-
3.
Metalloestrogens exposure and risk of gestational diabetes mellitus: Evidence emerging from the systematic review and meta-analysis.
Wu, W, Ren, J, Wang, J, Wang, J, Yu, D, Zhang, Y, Zeng, F, Huang, B
Environmental research. 2024;:118321
Abstract
BACKGROUND Metalloestrogens are metals and metalloid elements with estrogenic activity found everywhere. Their impact on human health is becoming more apparent as human activities increase. OBJECTIVE Our aim is to conduct a comprehensive systematic review and meta-analysis of observational studies exploring the correlation between metalloestrogens (specifically As, Sb, Cr, Cd, Cu, Se, Hg) and Gestational Diabetes Mellitus (GDM). METHODS PubMed, Web of Science, and Embase were searched to examine the link between metalloestrogens (As, Sb, Cr, Cd, Cu, Se, and Hg) and GDM until December 2023. Risk estimates were derived using random effects models. Subgroup analyses were conducted based on study countries, exposure sample, exposure assessment method, and detection methods. Sensitivity analyses and adjustments for publication bias were carried out to assess the strength of the findings. RESULTS Out of the 389 articles identified initially, 350 met our criteria and 33 were included in the meta-analysis, involving 141,175 subjects (9450 cases, 131,725 controls). Arsenic, antimony, and copper exposure exhibited a potential increase in GDM risk to some extent (As: OR = 1.28, 95 % CI [1.08, 1.52]; Sb: OR = 1.73, 95 % CI [1.13, 2.65]; Cu: OR = 1.29, 95 % CI [1.02, 1.63]), although there is a high degree of heterogeneity (As: Q = 52.93, p < 0.05, I2 = 64.1 %; Sb: Q = 31.40, p < 0.05, I2 = 80.9 %; Cu: Q = 21.14, p < 0.05, I2 = 71.6 %). Conversely, selenium, cadmium, chromium, and mercury exposure did not exhibit any association with the risk of GDM in our study. DISCUSSION Our research indicates that the existence of harmful metalloestrogens in the surroundings has a notable effect on the likelihood of GDM. Hence, we stress the significance of environmental elements in the development of GDM and the pressing need for relevant policies and measures.
-
4.
Decoding the gene regulatory network of endosperm differentiation in maize.
Yuan, Y, Huo, Q, Zhang, Z, Wang, Q, Wang, J, Chang, S, Cai, P, Song, KM, Galbraith, DW, Zhang, W, et al
Nature communications. 2024;(1):34
Abstract
The persistent cereal endosperm constitutes the majority of the grain volume. Dissecting the gene regulatory network underlying cereal endosperm development will facilitate yield and quality improvement of cereal crops. Here, we use single-cell transcriptomics to analyze the developing maize (Zea mays) endosperm during cell differentiation. After obtaining transcriptomic data from 17,022 single cells, we identify 12 cell clusters corresponding to five endosperm cell types and revealing complex transcriptional heterogeneity. We delineate the temporal gene-expression pattern from 6 to 7 days after pollination. We profile the genomic DNA-binding sites of 161 transcription factors differentially expressed between cell clusters and constructed a gene regulatory network by combining the single-cell transcriptomic data with the direct DNA-binding profiles, identifying 181 regulons containing genes encoding transcription factors along with their high-confidence targets, Furthermore, we map the regulons to endosperm cell clusters, identify cell-cluster-specific essential regulators, and experimentally validated three predicted key regulators. This study provides a framework for understanding cereal endosperm development and function at single-cell resolution.
-
5.
Natural products and derivatives in renal, urothelial and testicular cancers: Targeting signaling pathways and therapeutic potential.
Li, D, Wang, J, Tuo, Z, Yoo, KH, Yu, Q, Miyamoto, A, Zhang, C, Ye, X, Wei, W, Wu, R, et al
Phytomedicine : international journal of phytotherapy and phytopharmacology. 2024;:155503
Abstract
BACKGROUND Natural products have demonstrated significant potential in cancer drug discovery, particularly in renal cancer (RCa), urothelial carcinoma (UC), and testicular cancer (TC). PURPOSE This review aims to examine the effects of natural products on RCa, UC and TC. STUDY DESIGN systematic review METHODS PubMed and Web of Science databases were retrieved to search studies about the effects of natural products and derivatives on these cancers. Relevant publications in the reference list of enrolled studies were also checked. RESULTS This review highlighted their diverse impacts on key aspects such as cell growth, apoptosis, metastasis, therapy response, and the immune microenvironment. Natural products not only hold promise for novel drug development but also enhance the efficacy of existing chemotherapy and immunotherapy. Importantly, we exert their effects through modulation of critical pathways and target genes, including the PI3K/AKT pathway, NF-κB pathway, STAT pathway and MAPK pathway, among others in RCa, UC, and TC. CONCLUSION These mechanistic insights provide valuable guidance for researchers, facilitating the selection of promising natural products for cancer management and offering potential avenues for further gene regulation studies in the context of cancer treatment.
-
6.
Safety and efficacy of melatonin supplementation as an add-on treatment for infantile epileptic spasms syndrome: A randomized, placebo-controlled, double-blind trial.
Sun, Y, Chen, J, Shi, X, Li, Z, Wan, L, Yan, H, Chen, Y, Wang, J, Wang, J, Zou, L, et al
Journal of pineal research. 2024;(1):e12922
Abstract
This was a prospective, randomized, double-blind, single-center placebo-controlled trial to assess the efficacy and safety of melatonin as an add-on treatment for infantile epileptic spasms syndrome (IESS). Participants aged 3 months to 2 years with a primary diagnosis of IESS were recruited and assigned to two groups in a 1:1 ratio. Both treatment groups received a combination of adrenocorticotrophic hormone (ACTH) and magnesium sulfate (MgSO4 ) for 2 weeks, and the treatment group also received melatonin (3 mg) between 20:00 and 21:00 daily, 0.5-1 h before bedtime. The study's primary endpoint was the average reduction rate in spasm frequency assessed by seizure diaries. Secondary endpoints included assessment of the response rate, EEG hypsarrhythmia (Kramer score), and psychomotor development (Denver Developmental Screening Test, DDST). Sleep quality was assessed by using the Brief Infant Sleep Questionnaire (BISQ), the Infant Sleep Assessment Scale (ISAS), and actigraphy. Safety parameters were also evaluated. Statistical analyses were conducted on intention-to-treat and per-protocol populations. The trial is registered at Clinicaltrials.gov (ChiCTR2000036208). Out of 119 screened patients, 70 were randomized and 66 completed treatments. In the intention-to-treat population, there were no significant differences in the average percentage reduction of spasm frequency (median [interquartile range, IQR: Q3-Q1], 100% [46.7%] vs. 66.7% [55.3%], p = .288), the 3-day response rate (51.4% vs. 37.1%, p = .229), the 28-day response rate (42.9% vs. 28.6%, p = .212), EEG Kramer scores (2 [3.5] vs. 2 [3], p = .853), or DDST comprehensive months (5 [2.5] vs. 6 [6], p = .239) between the melatonin (n = 35) and placebo (n = 35) groups. However, caregivers reported improved sleep quality after melatonin treatment, with 85.7% reporting regular sleep compared to 42.9% with placebo (42.9%, p < .001). The melatonin group had lower ISAS scores in 4-11-month-old patients compared to the placebo (mean ± SD, 29.3 ± 4.4 vs. 35.2 ± 5.9, p < .001). Moreover, the median (IQR) value of sleep-onset latency was shortened by 6.0 (24.5) min after melatonin treatment, while that in the placebo group was extended by 3.0 (22.0) min (p = .030). The serum melatonin (6:00 h) level (pg/mL) of the children in the melatonin group after treatment was significantly higher than in the placebo group (median [IQR], 84.8 [142] vs. 17.5 [37.6], p < .001). No adverse effects related to melatonin were observed in the study, and there were no significant differences in adverse effects between the melatonin and placebo groups. Although not statistically significant, the results of this randomized clinical trial proved that melatonin supplementation, as an add-on treatment, can improve spasm control rate in the treatment of IESS. For IESS children treated with ACTH, the addition of melatonin was found to improve sleep quality, shorten sleep onset latency, and increase blood melatonin levels. Moreover, it was observed to be a safe treatment option.
-
7.
Occupancy Analysis of Water Molecules inside Channels within 25 Å Radius of the Oxygen-Evolving Center of Photosystem II in Molecular Dynamics Simulations.
Kaur, D, Reiss, K, Wang, J, Batista, VS, Brudvig, GW, Gunner, MR
The journal of physical chemistry. B. 2024;(10):2236-2248
Abstract
At room temperature and neutral pH, the oxygen-evolving center (OEC) of photosystem II (PSII) catalyzes water oxidation. During this process, oxygen is released from the OEC, while substrate waters are delivered to the OEC and protons are passed from the OEC to the lumen through water channels known as the narrow or the O4 channel, broad or the Cl1 channel, and large or the O1 channel. Protein residues lining the surfaces of these channels play a critical role in stabilizing the hydrogen-bonding networks that assist in the process. We carried out an occupancy analysis to better understand the structural and possible substrate water dynamics in full PSII monomer molecular dynamics (MD) trajectories in both the S1 and S2 states. We find that the equilibrated positions of water molecules derived from MD-derived electron density maps largely match the experimentally observed positions in crystallography. Furthermore, the occupancy reduction in MD simulations of some water molecules inside the single-filed narrow channel also correlates well with the crystallographic data during a structural transition when the S1 state of the OEC advances to the S2 state. The overall reduced occupancies of water molecules are the source of their "vacancy-hopping" dynamic nature inside these channels, unlike water molecules inside an ice lattice where all water molecules have a fixed unit occupancy. We propose on the basis of findings in our structural and molecular dynamics analysis that the water molecule occupying a pocket formed by D1-D61, D1-S169, and O4 of the OEC could be the last steppingstone to enter into the OEC and that the broad channel may be favored for proton transfer.
-
8.
Research progress on the physiological response and molecular mechanism of cold response in plants.
Wang, Y, Wang, J, Sarwar, R, Zhang, W, Geng, R, Zhu, KM, Tan, XL
Frontiers in plant science. 2024;:1334913
Abstract
Low temperature is a critical environmental stress factor that restricts crop growth and geographical distribution, significantly impacting crop quality and yield. When plants are exposed to low temperatures, a series of changes occur in their external morphology and internal physiological and biochemical metabolism. This article comprehensively reviews the alterations and regulatory mechanisms of physiological and biochemical indices, such as membrane system stability, redox system, fatty acid content, photosynthesis, and osmoregulatory substances, in response to low-temperature stress in plants. Furthermore, we summarize recent research on signal transduction and regulatory pathways, phytohormones, epigenetic modifications, and other molecular mechanisms mediating the response to low temperatures in higher plants. In addition, we outline cultivation practices to improve plant cold resistance and highlight the cold-related genes used in molecular breeding. Last, we discuss future research directions, potential application prospects of plant cold resistance breeding, and recent significant breakthroughs in the research and application of cold resistance mechanisms.
-
9.
Leveraging molecular targeted drugs and immune checkpoint inhibitors treat advanced thyroid carcinoma to achieve thyroid carcinoma redifferentiation.
Su, JY, Huang, T, Zhang, JL, Lu, JH, Wang, ML, Yan, J, Lin, RB, Lin, SY, Wang, J
American journal of cancer research. 2024;(2):407-428
Abstract
Thyroid cancer can be classified into three different types based on the degree of differentiation: well-differentiated, poorly differentiated, and anaplastic thyroid carcinoma. Well-differentiated thyroid cancer refers to cancer cells that closely resemble normal thyroid cells, while poorly differentiated and anaplastic thyroid carcinoma are characterized by cells that have lost their resemblance to normal thyroid cells. Advanced thyroid carcinoma, regardless of its degree of differentiation, is known to have a higher likelihood of disease progression and is generally associated with a poor prognosis. However, the process through which well-differentiated thyroid carcinoma transforms into anaplastic thyroid carcinoma, also known as "dedifferentiation", has been a subject of intensive research. In recent years, there have been significant breakthroughs in the treatment of refractory advanced thyroid cancer. Clinical studies have been conducted to evaluate the efficacy and safety of molecular targeted drugs and immune checkpoint inhibitors in the treatment of dedifferentiated thyroid cancer. These drugs work by targeting specific molecules or proteins in cancer cells to inhibit their growth or by enhancing the body's immune response against the cancer cells. This article aims to explore some of the possible mechanisms behind the dedifferentiation process in well-differentiated thyroid carcinoma. It also discusses the clinical effects of molecular targeted drugs and immune checkpoint inhibitors in thyroid cancer patients with different degrees of differentiation. Furthermore, it offers insights into the future trends in the treatment of advanced thyroid cancer, highlighting the potential for improved outcomes and better patient care.
-
10.
The emerging roles of next-generation metabolomics in critical care nutrition.
Li, K, Tong, HHY, Chen, Y, Sun, Y, Wang, J
Critical reviews in food science and nutrition. 2024;(5):1213-1224
Abstract
Critical illness leads to millions of deaths worldwide each year, with a significant surge due to the COVID-19 pandemic. Patients with critical illness are frequently associated with systemic metabolic disorders and malnutrition. The idea of intervention for critically ill patients through enteral and parenteral nutrition has been paid more and more attention gradually. However, current nutritional therapies focus on evidence-based practice, and there have been lacking holistic approaches for nutritional support assessment. Metabolomics is a well-established omics technique in system biology that enables comprehensive profiling of metabolites in a biological system and thus provides the underlying information expressed and modulated by all other omics layers. In recent years, with the development of high-resolution and accurate mass spectrometry, metabolomics entered a new "generation", promoting its broader applications in critical care nutrition. In this review, we first described the technological development and milestones of next-generation metabolomics in the past 20 years. We then discussed the emerging roles of next-generation metabolomics in advancing our understanding of critical care nutrition, such as nutritional deficiency risk evaluation, metabolic mechanisms of nutritional therapies, and novel nutrition target identification.