Crosstalk between brassinosteroids and other phytohormones during plant development and stress adaption.

Brassinosteroids (BRs) are a group of polyhydroxylated phytosterols that play essential roles in regulating plant growth and development as well as stress adaptation. It is worth noting that BRs do not function alone, but rather they crosstalk with other endogenous signaling molecules, including the phytohormones auxin, cytokinins (CKs), gibberellins (GAs), abscisic acid (ABA), ethylene (ET), jasmonates (JAs), salicylic acid (SA), and strigolactones (SLs), forming elaborate signaling networks to modulate plant growth and development. BRs interact with other phytohormones mainly by regulating each others' homeostasis, transport, or signaling pathway at the transcriptional and posttranslational levels. In this review, we focus our attention on current research progress in BR signal transduction and the crosstalk between BRs and other phytohormones.

Jasmonates regulate apical hook development by repressing brassinosteroid biosynthesis and signaling.

An apical hook is a special structure formed during skotomorphogenesis in dicotyledonous plant species. It is critical for protecting the shoot apical meristem from mechanical damage during seed germination and hypocotyl elongation in soil. Brassinosteroid (BR) and jasmonate (JA) phytohormones antagonistically regulate apical hook formation. However, the interrelationship between BRs and JAs in this process has not been well elucidated. Here, we reveal that JAs repress BRs to regulate apical hook development in Arabidopsis (Arabidopsis thaliana). Exogenous application of methyl jasmonate (MeJA) repressed the expression of the rate-limiting BR biosynthetic gene DWARF4 (DWF4) in a process relying on 3 key JA-dependent transcription factors, MYC2, MYC3, and MYC4. We demonstrated that MYC2 interacts with the critical BR-activated transcription factor BRASSINAZOLE RESISTANT 1 (BZR1), disrupting the association of BZR1 with its partner transcription factors, such as those of the PHYTOCHROME INTERACTING FACTOR (PIF) family and downregulating the expression of their target genes, such as WAVY ROOT GROWTH 2 (WAG2), encoding a protein kinase essential for apical hook development. Our results indicate that JAs not only repress the expression of BR biosynthetic gene DWF4 but, more importantly, attenuate BR signaling by inhibiting the transcriptional activation of BZR1 by MYC2 during apical hook development.

Gastroesophageal Reflux Disease and Rhinosinusitis: A Bidirectional Mendelian Randomization Study.

INTRODUCTION: Comorbidities, such as gastroesophageal reflux disease (GERD), are common in patients with rhinosinusitis (RS). However, the link between RS and GERD has not been fully understood. This study aimed to investigate the causal relationship between GERD and acute (ARS) or chronic RS (CRS), providing references for the pathogenesis and management of RS. METHODS: The data were obtained from the Integrative Epidemiology Unit Open GWAS project and FinnGen. A total of 972,838 individuals were included. The inverse variance-weighted (IVW) method was applied to obtain the primary results of the study. Weighted median, MR-Egger, and mode-based methods were used to determine the robustness of the results. Cochran's Q statistic and MR-Egger method were applied to detect heterogeneity and pleiotrophy in instrumental variables (IVs). Other sensitivity analyses included MR-PRESSO and leave-one-out analysis. RESULTS: The MR study showed that GERD was associated with an increased risk of CRS (OR: 1.36, 95% CI: 1.18-1.57, p < 0.001). The results of other analysis methods were broadly consistent with the IVW estimate. No heterogeneity was detected by Cochran's Q test (p = 0.061) and MR-PRESSO (p = 0.074). No horizontal pleiotropy was shown in IVs (p = 0.700). GERD was also associated with an increased risk of ARS (OR: 1.31, 95% CI: 1.17-1.48, p < 0.001). Some analytical results were inconsistent with the IVW estimate. No heterogeneity and pleiotropy were observed. There was no sufficient evidence for a reverse causal effect of RS on GERD. CONCLUSION: Our study supported that GERD promoted the risk of CRS and may be a potential risk factor for ARS. This provides additional support for further investigation into the mechanisms of GERD on RS.

Precisely Engineering Asymmetric Atomic CoN4 by Electron Donating and Extracting for Oxygen Reduction Reaction.

The development of nonpyrolytic catalysts featuring precisely defined active sites represents an effective strategy for investigating the fundamental relationship between the catalytic activity of oxygen reduction reaction (ORR) catalysts and their local coordination environments. In this study, we have synthesized a series of model electrocatalysts with well-defined CoN4 centers and nonplanar symmetric coordination structures. These catalysts were prepared by a sequential process involving the chelation of cobalt salts and 1,10-phenanthroline-based ligands with various substituent groups (phen(X), where X=OH, CH3, H, Br, Cl) onto covalent triazine frameworks (CTFs). By modulating the electron-donating or electron-withdrawing properties of the substituent groups on the phen-based ligands, the electron density surrounding the CoN4 centers was effectively controlled. Our results demonstrated a direct correlation between the catalytic activity of the CoN4 centers and the electron-donating ability of the substituent group on the phenanthroline ligands. Notably, the catalyst denoted as BCTF-Co-phen(OH), featuring the electron-donating OH group, exhibited the highest ORR catalytic activity. This custom-crafted catalyst achieved a remarkable half-wave potential of up to 0.80 V vs. RHE and an impressive turnover frequency (TOF) value of 47.4×10-3 Hz at 0.80 V vs. RHE in an alkaline environment.

The EPFL-ERf-SERK signaling controls integument development in Arabidopsis.

As the seed precursor, the ovule produces the female gametophyte (or embryo sac), and the subsequent double fertilization occurs in it. The integuments emerge sequentially from the integument primordia at the early stages of ovule development and finally enwrap the embryo sac gradually during gametogenesis, protecting and nursing the embryo sac. However, the mechanisms regulating integument development are still obscure. In this study, we show that SOMATIC EMBRYOGENESIS RECEPTOR-LIKE KINASES (SERKs) play essential roles during integument development in Arabidopsis thaliana. The serk1/2/3 triple mutant shows arrested integuments and abnormal embryo sacs, similar defects also found in the triple loss-of-function mutants of ERECTA family (ERf) genes. Ovules of serk1/2/3 er erl1/2 show defects similar to er erl1/2 and serk1/2/3. Results of yeast two-hybrid analyses, bimolecular fluorescence complementation (BiFC) analyses, and co-immunoprecipitation assays demonstrated that SERKs interact with ERf, which depends on EPIDERMAL PATTERNING FACTOR-LIKE (EPFL) family small peptides. The sextuple mutant epfl1/2/3/4/5/6 shows integument defects similar to both of er erl1/2 and serk1/2/3. Our results demonstrate that ERf-SERK-mediated EPFL signaling orchestrates the development of the female gametophyte and the surrounding sporophytic integuments.

BES1/BZR1 Family Transcription Factors Regulate Plant Development via Brassinosteroid-Dependent and Independent Pathways.

The BES1/BZR1 family is a plant-specific small group of transcription factors possessing a non-canonical bHLH domain. Genetic and biochemical analyses within the last two decades have demonstrated that members of this family are key transcription factors in regulating the expression of brassinosteroid (BR) response genes. Several recent genetic and evolutionary studies, however, have clearly indicated that the BES1/BZR1 family transcription factors also function in regulating several aspects of plant development via BR-independent pathways, suggesting they are not BR specific. In this review, we summarize our current understanding of this family of transcription factors, the mechanisms regulating their activities, DNA binding motifs, and target genes. We selectively discuss a number of their biological functions via BR-dependent and particularly independent pathways, which were recently revealed by loss-of-function genetic analyses. We also highlight a few possible future directions.

SAUR15 Promotes Lateral and Adventitious Root Development via Activating H+-ATPases and Auxin Biosynthesis.

SMALL AUXIN-UP RNAs (SAURs) comprise the largest family of early auxin response genes. Some SAURs have been reported to play important roles in plant growth and development, but their functional relationships with auxin signaling remain unestablished. Here, we report Arabidopsis (Arabidopsis thaliana) SAUR15 acts downstream of the auxin response factors ARF6,8 and ARF7,19 to regulate auxin signaling-mediated lateral root (LR) and adventitious root (AR) formation. The loss-of-function mutant saur15-1 exhibits fewer LRs and ARs. By contrast, plants overexpressing SAUR15 exhibit more LRs and ARs. We find that the SAUR15 promoter contains four tandem auxin-responsive elements, which are directly bound by ARF6 and ARF7 and are essential for SAUR15 expression. LR and AR impairment in arf6 and arf7 mutants is partially reduced by ectopic expression of SAUR15 Additionally, we demonstrate that the ARF6,7-upregulated SAUR15 promotes LR and AR development using two mechanisms. On the one hand, SAUR15 interacts with PP2C-D subfamily type 2C protein phosphatases to inhibit their activities, thereby stimulating plasma membrane H+-ATPases, which drives cell expansion and facilitates LR and AR formation. On the other hand, SAUR15 promotes auxin accumulation, potentially by inducing the expression of auxin biosynthesis genes. A resulting increase in free auxin concentration likely triggers LR and AR formation, forming a feedback loop. Our study provides insights and a better understanding of how SAURs function at the molecular level in regulating auxin-mediated LR and AR development.

Protein farnesylation negatively regulates brassinosteroid signaling via reducing BES1 stability in Arabidopsis thaliana.

Brassinosteroids (BRs) are a group of steroidal phytohormones, playing critical roles in almost all physiological aspects during the life span of a plant. In Arabidopsis, BRs are perceived at the cell surface, triggering a reversible phosphorylation-based signaling cascade that leads to the activation and nuclear accumulation of a family of transcription factors, represented by BES1 and BZR1. Protein farnesylation is a type of post-translational modification, functioning in many important cellular processes. Previous studies demonstrated a role of farnesylation in BR biosynthesis via regulating the endoplasmic reticulum localization of a key bassinolide (BL) biosynthetic enzyme BR6ox2. Whether such a process is also involved in BR signaling is not understood. Here, we demonstrate that protein farnesylation is involved in mediating BR signaling in Arabidopsis. A loss-of-function mutant of ENHANCED RESPONSE TO ABA 1 (ERA1), encoding a ß subunit of the protein farnesyl transferase holoenzyme, can alter the BL sensitivity of bak1-4 from a reduced to a hypersensitive level. era1 can partially rescue the BR defective phenotype of a heterozygous mutant of bin2-1, a gain-of-function mutant of BIN2 which encodes a negative regulator in the BR signaling. Our genetic and biochemical analyses revealed that ERA1 plays a significant role in regulating the protein stability of BES1.

Molecular Mechanisms of Brassinosteroid-Mediated Responses to Changing Environments in Arabidopsis.

Plant adaptations to changing environments rely on integrating external stimuli into internal responses. Brassinosteroids (BRs), a group of growth-promoting phytohormones, have been reported to act as signal molecules mediating these processes. BRs are perceived by cell surface receptor complex including receptor BRI1 and coreceptor BAK1, which subsequently triggers a signaling cascade that leads to inhibition of BIN2 and activation of BES1/BZR1 transcription factors. BES1/BZR1 can directly regulate the expression of thousands of downstream responsive genes. Recent studies in the model plant Arabidopsis demonstrated that BR biosynthesis and signal transduction, especially the regulatory components BIN2 and BES1/BZR1, are finely tuned by various environmental cues. Here, we summarize these research updates and give a comprehensive review of how BR biosynthesis and signaling are modulated by changing environments and how these changes regulate plant adaptive growth or stress tolerance.

Groundwater hydrogeochemical formation and evolution in a karst aquifer system affected by anthropogenic impacts.

Karst groundwater, an important water source, is often highly influenced by human impacts, causing environmental damage and threats to human health. However, studies on the anthropogenic influences on the hydrogeochemical evolution of karst groundwater are relatively rare. To assess hydrogeochemical formation and evolution, we focused on a typical karst groundwater system (Jinan, China) which is composed of cold groundwater (av. temperature 13-17 °C), springs and geothermal water (av. temperature > 30 °C) and is significantly affected by human activities. The study was performed by means of water samples collecting and analyzing and isotope analysis (2H, 18O and 14C). The statistical analysis and inverse models were also applied to further understand geochemical processes and anthropogenic influences. The 2H, 18O and 14C results indicate that the cold karst groundwater is easily influenced and contaminated by the local environment, while geothermal water is relatively old with a slow rate of recharge. The hydrochemical types of cold karst groundwater are mainly HCO3-Ca and HCO3·SO4-Ca, while geothermal water hydrochemical types are SO4-Ca·Na and SO4-Ca. Groundwater Ca2+, Mg2+, HCO3- and SO42- are mainly controlled by carbonate equilibrium, gypsum dissolution and dedolomitization. Groundwater Na+, K+ and Cl- are mainly derived from halite dissolution, and in geothermal water, they are also affected by incongruent dissolution of albite and K-feldspar. Anthropogenic nitrogen produces ammonium resulting in nitrification and reduction in CO2(g) consumption and HCO3- release from carbonate dissolution. Principal component analysis and inverse models also indicate that nitrification and denitrification have significantly affected water-rock interactions. Our study suggests that karst groundwater quality is dominated by water-rock interactions and elucidates the influence of anthropogenic nitrogen. We believe that this paper will be a good reference point to study anthropogenic influences on the groundwater environment and to protect karst groundwater globally.

Scanning for New BRI1 Mutations via TILLING Analysis.

The identification and characterization of a mutational spectrum for a specific protein can help to elucidate its detailed cellular functions. BRASSINOSTEROID INSENSITIVE1 (BRI1), a multidomain transmembrane receptor-like kinase, is a major receptor of brassinosteroids in Arabidopsis (Arabidopsis thaliana). Within the last two decades, over 20 different bri1 mutant alleles have been identified, which helped to determine the significance of each domain within BRI1. To further understand the molecular mechanisms of BRI1, we tried to identify additional alleles via targeted induced local lesions in genomes. Here, we report our identification of 83 new point mutations in BRI1, including nine mutations that exhibit an allelic series of typical bri1 phenotypes, from subtle to severe morphological alterations. We carried out biochemical analyses to investigate possible mechanisms of these mutations in affecting brassinosteroid signaling. A number of interesting mutations have been isolated via this study. For example, bri1-702, the only weak allele identified so far with a mutation in the activation loop, showed reduced autophosphorylation activity. bri1-705, a subtle allele with a mutation in the extracellular portion, disrupts the interaction of BRI1 with its ligand brassinolide and coreceptor BRI1-ASSOCIATED RECEPTOR KINASE1. bri1-706, with a mutation in the extracellular portion, is a subtle defective mutant. Surprisingly, root inhibition analysis indicated that it is largely insensitive to exogenous brassinolide treatment. In this study, we found that bri1-301 possesses kinase activity in vivo, clarifying a previous report arguing that kinase activity may not be necessary for the function of BRI1. These data provide additional insights into our understanding of the early events in the brassinosteroid signaling pathway.

Detection of GSK-3ß activation index in pediatric chronic tonsillitis is an indicator for chronic recurrent inflammation.

PURPOSE: Chronic tonsillitis (TC) is among the most common bacterial diseases in pediatric otolaryngology. We aimed to evaluate the expression of glycogen synthase kinase 3ß (GSK-3ß) in a cohort of children with chronic tonsillitis (TC), and the correlation between GSK-3ß activity index and inflammatory profiles of TC. MATERIALS AND METHODS: The expression of GSK-3ß was comparably evaluated between children with TC (n = 26) and tonsillar hypertrophy (TH, n = 26). GSK-3ß expression was detected by immunohistochemistry, RT-qPCR, and Western blot. The inflammatory profiles between the TC and TH groups were also evaluated. RESULTS: We found that while GSK-3ß was highly expressed in both TC and TH groups, no significant difference were detected at mRNA and protein levels between groups. The protein level of p-GSK-3ß was significantly lower in the TC group as compared to the TH group. Additionally, the inflammatory markers, including NF-κB, T-bet, and IFN-γ were higher in the TC group compared to TH group. The GSK-3ß activation index was positively correlated with the levels of NF-κB, T-bet, and IFN-γ in the TC group. CONCLUSIONS: Our findings suggested that GSK-3ß activation index was demonstrated to be a clinically applicable indicator for chronic recurrent inflammation in pediatric TC.

[Effect of different concentrations of calcitonin gene-related peptide on the long-term potentiation in hippocampus of mice].

The purpose of this study was to explore the effects of different concentrations of calcitonin gene-related peptide (CGRP) on long-term potentiation (LTP) in the hippocampus of mice. C57BL/6J mice (30 days old) were randomly divided into control group, three CGRP groups, and CGRP + CGRP8-37 group (10 mice for each group). Different concentrations of CGRP (50, 100 and 200 nmol/L) were given to the hippocampal slices of mice. The presynaptic release of neurotransmitters and the induction of LTP were measured by extracellular field recording techniques. The result showed that different concentrations of CGRP did not affect the presynaptic release of neurotransmitters, but 100 and 200 nmol/L CGRP increased the amplitude of LTP induced in the hippocampus of mice. This facilitation effect of CGRP was blocked by its specific antagonist CGRP8-37. These results suggest that CGRP dose-dependently facilitates the induction of LTP in the hippocampus of mice through its specific receptor.

[Effect of bilateral injection of calcitonin gene-related peptide into amygdala on learning and memory of mice].

The aim of the present study was to explore the effects of different doses of calcitonin gene-related peptide (CGRP) injected into the central nucleus of amygdala on cognitive function, learning and memory of mice. C57BL/6J mice (30 days old) were randomly divided into control, sham, and three CGRP groups (10 mice for each group). Three doses of CGRP (200, 400 and 800 ng) were bilaterally administered into the central nucleus of the amygdala. Open field test was used to assess cognitive function. Novel object recognition and Morris water maze test were used to evaluate learning and memory of the mice. The results of open field test showed that 800 ng CGRP significantly increased the locomotive score. The results of novel objective recognition test showed that 400 ng CGRP significantly increased the recognition index. Compared with control group, 400 and 800 ng CGRP groups showed significantly shortened latency period and increased crossing times. Simultaneously, the latency periods of 400 and 800 ng CGRP groups were shorter than that of 200 ng CGRP group. These results suggest that bilateral injection of CGRP into amygdala dose-dependently enhances the learning and memory function of mice.

Preparation of Phosphorylated Auricularia cornea var. Li. Polysaccharide Liposome Gel and Analysis of Its In Vitro Antioxidant Activity.

In this study, Auricularia cornea var. Li. polysaccharides (ACP) were used as the research object to prepare liposome gel and determine its antioxidant activity in vitro. Phosphorylated Auricularia cornea var. Li. polysaccharides (P-ACP) were prepared via the phosphorylation of ACP by the phosphate method. Additionally, phosphorylated Auricularia cornea var. Li. polysaccharide liposomes (P-ACPL) were prepared using a reverse evaporation method. Finally, phosphorylated Auricularia cornea var. Li. polysaccharide liposome gel (P-ACPLG) was prepared by dispersing the P-ACPL in the gel matrix. The results show that the phosphorylation of the P-ACP was 15.51%, the containment rate of the P-ACPL was 84.50%, the average particle size was (192.2 ± 3.3) nm, and the particle size distribution map had a homogeneous peak, resulting in the particle dispersion being uniform and the polydispersion index (PDI) being 0.134 ± 0.021. The average Zeta potential was (-33.4 ± 0.57) mV. In addition, the in vitro antioxidant activity of the P-ACPL was slightly higher than that of the ACP and P-ACP. After the P-ACPL was emulsified into P-ACPLG, the DPPH, hydroxyl radical clearance, and reducing the ability of P-ACPL remained unchanged. In general, the P-ACPLG prepared in this study has good antioxidant activity in vitro and can retain the antioxidant activity of P-ACPL in vitro well.

Low-molecular-weight aromatic acids mediated the adsorption of Cd2+ onto biochars: effects and mechanisms.

Low-molecular-weight aromatic acids (LWMAAs), a ubiquitous organic substance in natural systems, are important in controlling the environmental fate of potentially toxic metals. However, little is known about the effects of LWMAAs on the interactions between biochars and potentially toxic metals. Herein, the influences of three aromatic acids, including benzoic acid (BA), p-hydroxy benzoic acid (PHBA), and syringic acid (SA), on the adsorption of Cd2+ onto biochars generated at three different pyrolysis temperatures under acidic and neutral conditions were examined. Generally, the adsorption ability of biochars for Cd2+ improved with the increase of pyrolysis temperature, which was ascribed to the increased inorganic element contents (e.g., P, S, and Si) and aromaticity, increasing the complexation between mineral anions and metal ions, and the enhanced cation-π interaction. Interestingly, aromatic acids considerably inhibited the adsorption of Cd2+ onto biochars, which was mainly ascribed to multi-mechanisms, including competition of LWMAA molecules and metal ions for adsorption sites, the pore blocking effect, the weakened interaction between mineral anions and Cd2+ induced by the adsorbed aromatic acids, and the formation of water-soluble metal-aromatic acid complexes. Furthermore, the inhibitory effects of LWMAAs on Cd2+ adsorption intensively depended on the aromatic acid type and followed the order of SA > PHBA > BA. This trend was related to the differences in the physicochemical features (e.g., the octanol/water partition coefficient (log Kow) and molecular size) of diverse LMWAAs. The results of this study demonstrate that the effects of coexisting LMWAAs should not be ignored when biochars are applied in soil remediation and wastewater treatment.

Bimetallic-Coordinated Covalent Triazine Framework-Derived FeNi Alloy Nanoparticle-Decorated Coral-Like Nanocarbons for Oxygen Electrocatalysis.

It is highly desirable to fabricate transition bimetallic alloy-embedded porous nanocarbons with a unique nanoarchitecture for the oxygen evolution reaction (OER) and oxygen reduction reaction (ORR) in rechargeable zinc-air batteries. In this work, we introduce a template-assisted in situ alloying synthesis of FeNi alloy nanoparticle-decorated coral-like nanocarbons (FeNi-CNCs) as efficient OER/ORR dual-functional electrocatalysts. The present materials are produced through polycondensation of a covalent triazine framework (CTF), the coordination of Ni and Fe ions, and sequential pyrolytic treatment. Through the pyrolysis process, the nanolamellar FeNi-CTF precursors can be facilely converted into FeNi alloy nanoparticle-decorated nanocarbons. These nanocarbons possess a distinctive three-dimensional (3D) coral-like nanostructure, which is favorable for the transport of oxygen and the diffusion of electrolyte. As a result, FeNi-CNC-800 with the highest efficiency exhibited remarkable electrocatalytic performance and great durability. Additionally, it also can be assembled into rechargeable zinc-air batteries that can be assembled in both liquid and solid forms, offering a superior peak power density, large specific capacity, and outstanding reusability during charging/discharging cycles (e.g., 5160 charging-and-discharging cycles at 10 mA cm-2 for the liquid forms). These traits make it a highly promising option in the burgeoning field of wearable energy conversion.

Amorphous MnO2 Lamellae Encapsulated Covalent Triazine Polymer-Derived Multi-Heteroatoms-Doped Carbon for ORR/OER Bifunctional Electrocatalysis.

The intelligent construction of non-noble metal materials that exhibit reversible oxygen reduction reaction (ORR) and oxygen evolution reaction (OER) with bifunctional electrocatalytic performance is greatly coveted in the realm of zinc-air batteries (ZABs). Herein, a crafted structure-amorphous MnO2 lamellae encapsulated covalent triazine polymer-derived N, S, P co-doped carbon sphere (A-MnO2/NSPC) is designed using a self-doped pyrolysis coupled with an in situ encapsulation strategy. The customized A-MnO2/NSPC-2 demonstrates a superior bifunctional electrocatalytic performance, confirmed by a small ΔE index of 0.64 V for ORR/OER. Experimental investigations, along with density functional theory calculations validate that predesigned amorphous MnO2 surface defects and abundant heteroatom catalytic active sites collectively enhance the oxygen electrocatalytic performance. Impressively, the A-MnO2/NSPC-based rechargeable liquid ZABs show a large open-circuit potential of 1.54 V, an ultrahigh peak power density of 181 mW cm-2, an enormous capacity of 816 mAh g-1, and a remarkable stability for more than 1720 discharging/charging cycles. Additionally, the assembled flexible all-solid-state ZABs also demonstrate outstanding cycle stability, surpassing 140 discharging/charging cycles. Therefore, this highly operable synthetic strategy offers substantial understanding in the development of magnificent bifunctional electrocatalysts for various sustainable energy conversions and beyond.

Anti-inflammatory phytochemicals for the treatment of diabetes and its complications: Lessons learned and future promise.

Diabetes mellitus (type 1 and type 2) and its various complications continue to place a huge burden on global medical resources, despite the availability of numerous drugs that successfully lower blood glucose levels. The major challenging issue in diabetes management is the prevention of various complications that remain the leading cause of diabetes-related mortality. Moreover, the limited long-term durability of monotherapy and undesirable side effects of currently used anti-diabetic drugs underlie the urgent need for novel therapeutic approaches. Phytochemicals represent a rich source of plant-derived molecules that are of pivotal importance to the identification of compounds with therapeutic potential. In this review, we aim to discuss recent advances in the identification of a large array of phytochemicals with immense potential in the management of diabetes and its complications. Given that metabolic inflammation has been established as a key pathophysiological event that drives the progression of diabetes, we focus on the protective effects of representative phytochemicals in metabolic inflammation. This paper also discusses the potential of phytochemicals in the development of new drugs that target the inflammation in the management of diabetes and its complications.

Health risk assessment of groundwater nitrate contamination: a case study of a typical karst hydrogeological unit in East China.

Nitrate pollution in rivers, lakes, shallow groundwater, and even deep groundwater occurs in many parts of the world. And, it's essential to assessing the relationship between nitrate pollution and human health, which is called human health risk assessment (HHRA). In this paper, groundwater samples were collected for their nitrate content in a typical karst hydrogeological unit in East China during the wet and dry seasons. Then, a human health risk assessment was conducted using the four-step risk assessment process developed by the US Environmental Protection Agency (USEPA), which aimed to determine the potential risk posed to human health by nitrate in the groundwater. To make the assessment more authentic and objective, the drinking water and dermal contact exposure pathways were considered, and the people were divided into four groups, including infants (0~6 months), children (7 months~17 years old), females (18 years and older), and males (18 years and older), in the wet and dry seasons to determine the impacts of the exposure pathway, age, sex, and precipitation period. The results indicated that more than half of the groundwater samples exceeded 10 mg/L (measured as nitrogen), which is the drinking water standard of China. The children and infants had greater health risks than the adults at the same groundwater nitrate concentration, and those two groups need to be paid more attention; the adult females had a greater health risk than the adult males in the two precipitation periods, which shows that the order of the health risk was infants ˃ children ˃ adult females ˃ adult males. In addition, the value of the hazard quotient (HQ) and the area of the adverse effects were both higher in the wet season than in the dry season, which explains that precipitation can affect the human health risk as well. The HQ caused by the drinking water exposure pathway was much higher than that caused by the dermal contact exposure pathway. This study can provide information for more effective and reasonable decisions to city managers for groundwater nitrate pollution prevention.