Tauroursodeoxycholic acid ameliorates renal injury induced by COL4A3 mutation.

COL4A3/A4/A5 mutations have been identified as critical causes of Alport syndrome and other genetic chronic kidney diseases. However, the underlying pathogenesis remains unclear, and specific treatments are lacking. Here, we constructed a transgenic Alport syndrome mouse model by generating a mutation (Col4a3 p.G799R) identified previously from one large Alport syndrome family into mice. We observed that the mutation caused a pathological decrease in intracellular and secreted collagen IV α3α4α5 heterotrimers. The mutant collagen IV α3 chains abnormally accumulated in the endoplasmic reticulum and exhibited defective secretion, leading to persistent endoplasmic reticulum stress in vivo and in vitro. RNA-seq analysis revealed that the MyD88/p38 MAPK pathway plays key roles in mediating subsequent inflammation and apoptosis signaling activation. Treatment with tauroursodeoxycholic acid, a chemical chaperone drug that functions as an endoplasmic reticulum stress inhibitor, effectively suppressed endoplasmic reticulum stress, promoted secretion of the α3 chains, and inhibited the activation of the MyD88/p38 MAPK pathway. Tauroursodeoxycholic acid treatment significantly improved kidney function in vivo. These results partly clarified the pathogenesis of kidney injuries associated with Alport syndrome, especially in glomeruli, and suggested that tauroursodeoxycholic acid might be useful for the early clinical treatment of Alport syndrome.

Purinergic P2X7 receptor involves in anti-retinal photodamage effects of berberine.

Berberine (BBR) is a Chinese herb with antioxidant and anti-inflammatory properties. In a previous study, we found that BBR had a protective effect against light-induced retinal degeneration in BALB/c mice. The purinergic P2X7 receptor (P2X7R) plays a key role in retinal degeneration via inducing oxidative stress, inflammatory changes, and cell death. The aim of this study was to investigate whether BBR can induce protective effects in light damage experiments and whether P2X7R can get involved in these effects. C57BL/6 J mice and P2X7 knockout (KO) mice on the C57BL/6 J background were used. We found that BBR preserved the outer nuclear layer (ONL) thickness and retinal ganglion cells following light stimulation. Furthermore, BBR significantly suppressed photoreceptor apoptosis, pro-apoptotic c-fos expression, pro-inflammatory responses of Mϋller cells, and inflammatory factors (TNF-α, IL-1ß). In addition, protein levels of P2X7R were downregulated in BBR-treated mice. Double immunofluorescence showed that BBR reduced overexpression of P2X7R in retinal ganglion cells and Mϋller cells. Furthermore, BBR combined with the P2X7R agonist BzATP blocked the effects of BBR on retinal morphology and photoreceptor apoptosis. However, in P2X7 KO mice, BBR had an additive effect resulting in thicker ONL and more photoreceptors. The data suggest that the P2X7 receptor is involved in retinal light damage, and BBR inhibits this process by reducing histological impairment, cell death, and inflammatory responses.

Insights into the Enhanced Photogeneration of Hydroxyl Radicals from Chlorinated Dissolved Organic Matter.

Free available chlorine has been and is being applied in global water treatment and readily reacts with dissolved organic matter (DOM) in aquatic environments, leading to the formation of chlorinated products. Chlorination enhances the photoreactivity of DOM, but the influence of chlorinated compounds on the photogeneration of hydroxyl radicals (•OH) has remained unexplored. In this study, a range of chlorinated carboxylate-substituted phenolic model compounds were employed to assess their •OH photogeneration capabilities. These compounds demonstrated a substantial capacity for •OH production, exhibiting quantum yields of 0.1-5.9 × 10-3 through direct photolysis under 305 nm and 0.2-9.5 × 10-3 through a triplet sensitizer (4-benzoylbenzoic acid)-inducing reaction under 365 nm LED irradiation. Moreover, the chlorinated compounds exhibited higher light absorption and •OH quantum yields compared to those of their unchlorinated counterparts. The •OH photogeneration capacity of these compounds exhibited a positive correlation with their triplet state one-electron oxidation potentials. Molecular-level compositional analysis revealed that aromatic structures rich in hydroxyl and carboxyl groups (e.g., O/C > 0.5 with H/C < 1.5) within DOM serve as crucial sources of •OH, and chlorination of these compounds significantly enhances their capacity to generate •OH upon irradiation. This study provides novel insights into the enhanced photogeneration of •OH from chlorinated DOM, which is helpful for understanding the fate of trace pollutants in chlorinated waters.

P2X7 receptor-mediated depression-like reactions arising in the mouse medial prefrontal cortex.

Major depressive disorder is a frequent and debilitating psychiatric disease. We have shown in some of the acute animal models of major depressive disorder (tail suspension test and forced swim test) that depression-like behavior can be aggravated in mice by the microinjection into the medial prefrontal cortex of the P2X7R agonistic adenosine 5'-triphosphate or its structural analog dibenzoyl-ATP, and these effects can be reversed by the P2X7R antagonistic JNJ-47965567. When measuring tail suspension test, the prolongation of immobility time by the P2YR agonist adenosine 5'-[ß-thio]diphosphate and the reduction of the adenosine 5'-(γ-thio)triphosphate effect by P2Y1R (MRS 2179) or P2Y12R (PSB 0739) antagonists, but not by JNJ-47965567, all suggest the involvement of P2YRs. In order to elucidate the localization of the modulatory P2X7Rs in the brain, we recorded current responses to dibenzoyl-ATP in layer V astrocytes and pyramidal neurons of medial prefrontal cortex brain slices by the whole-cell patch-clamp procedure; the current amplitudes were not altered in preparations taken from tail suspension test or foot shock-treated mice. The release of adenosine 5'-triphosphate was decreased by foot shock, although not by tail suspension test both in the hippocampus and PFC. In conclusion, we suggest, that in the medial prefrontal cortex, acute stressful stimuli cause supersensitivity of P2X7Rs facilitating the learned helplessness reaction.

Molecular detection of Cryptosporidium in Alpine musk deer (Moschus chrysogaster) in Gansu Province, Northwest China.

Cryptosporidium spp. are protozoa commonly found in domestic and wild animals. Limited information is available on Cryptosporidium in deer worldwide. In this study, 201 fecal samples were collected from Alpine musk deer on three farms in Gansu Province, China. Detection and subtyping of Cryptosporidium were performed by PCR and sequence analysis of the SSU rRNA and gp60 genes. The prevalence of Cryptosporidium infection in Alpine musk deer was 3.9% (8/201), with infection rates of 1.0% (1/100), 2.8% (1/36), and 9.2% (6/65) in three different farms. All positive samples for Cryptosporidium were from adult deer. Two Cryptosporidium species were identified, including C. parvum (n = 2) and C. xiaoi (n = 6). The C. parvum isolates were subtyped as IIdA15G1, while the C. xiaoi isolates were subtyped as XXIIIa (n = 2) and XXIIIg (n = 4). The IIdA15G1 subtype of C. parvum was found for the first time in deer. These results provide important insights into the identity and human infectious potential of Cryptosporidium in farmed Alpine musk deer.

Study on the clinical effect of percutaneous transforaminal endoscopic discectomy combined with annulus fibrosus repair in the treatment of single-segment lumbar disc herniation in young and middle-aged patients.

Objective: To explore the clinical effect of percutaneous transforaminal endoscopic discectomy (PTED) combined with annulus fibrosus repair in the treatment of single-segment lumber disc herniation (LDH) in young and middle-aged patients. Methods: Ninty-six patients with single-segment LDH admitted to Baoding First Central Hospital from March 2021 to November 2022 were selected in the retrospective study. The patients were divided into endoscopic group and combined group according to different surgical methods. The surgical conditions, VAS score and ODI score the two groups of patients were compared, as well as the postoperative review results. Results: There were 50 patients in the endoscopic group the average operation time was 43.68 ± 10.77 minutes, the average intraoperative blood loss was 35.38 ± 10.02 ml, there were seven cases of surgical segment recurrence and 10 cases of postoperative intervertebral instability at the surgical segment. There were 46 patients in the combined group, the average operation time was 52.26 ± 8.39 minutes, the average intraoperative blood loss was 39.23 ± 9.02ml, there was one case of surgical segment recurrence and two cases of surgical segment intervertebral instability. The operation time (t=-4.328, P<0.01), postoperative recurrence cases (χ2=4.386, P<0.05) and intervertebral instability cases (χ2=5.366, P<0.05) of the two groups of patients). The difference was statistically significant. There was no significant difference in intraoperative blood loss between the two groups (t=-1.965, P>0.05). For six months after surgery, the differences in VAS and ODI scores between the two groups were statistically significant. In addition, there were statistically significant differences in the VAS scores and ODI scores of the two groups of patients at each time point after surgery compared with those before surgery (P<0.05). Conclusion: The clinical efficacy of PTED combined with annulus fibrosus repair showed better clinical efficacy than PTED alone, and it can reduce the occurrence of surgical segment recurrence and intervertebral instability, suggesting that PTED combined with annulus fibrosus repair may be worthy of promotion in clinical practice.

Plasma soluble tumor necrosis factor receptor I as a biomarker of lupus nephritis and disease activity in systemic lupus erythematosus patients.

OBJECTIVES: The goal of our study was to evaluate the potential role of sTNF-RI as a biomarker of renal involvement in SLE patients and active SLE. METHODS: The study sample consisted of two cohorts. The discovery cohort included 16 SLE patients without renal involvement (non-LN), 60 lupus nephritis (LN) patients and 21 healthy controls (HCs) and the replication cohort included 18 SLE non-LN patients, 116 LN patients and 36 HCs. RESULTS: The sTNF-RI levels differed significantly in the discovery cohort. The plasma sTNF-RI levels were higher in LN patients than in non-LN patients (p = .009) and HCs (p = 4 × 10-6). Plasma sTNF-RI levels were significantly higher in non-LN patients than in HCs (p = .03). The finding was confirmed in independent replication cohort (LNs vs. non-LN, p = 4.053 × 10-7; LNs vs. HCs, p = 2.395 × 10-18; non-LN vs. HCs, p = 2.51 × 10-4). The plasma sTNF-RI levels were associated with disease activity, renal function in SLE patients and urine protein in LN patients. The multivariate analysis revealed that high sTNF-RI was an independent risk factor for renal involvement. The multivariate logistic regression results suggested that high TNF-RI, high systolic blood pressure, high serum creatinine, low C4 and positive anti-dsDNA were independent risks of active SLE patients. A nomogram was constructed based on the results of multivariate logistic regression analysis and it was practical in predicting the risk of the active SLE patients. Immunohistochemistry suggested that the expression of TNF-RI in the kidney was increased. CONCLUSIONS: Plasma sTNF-RI might be a good biomarker of renal involvement and disease activity in SLE patients.

CD73: Friend or Foe in Lung Injury.

Ecto-5'-nucleotidase (CD73) plays a strategic role in calibrating the magnitude and chemical nature of purinergic signals that are delivered to immune cells. Its primary function is to convert extracellular ATP to adenosine in concert with ectonucleoside triphosphate diphosphohydrolase-1 (CD39) in normal tissues to limit an excessive immune response in many pathophysiological events, such as lung injury induced by a variety of contributing factors. Multiple lines of evidence suggest that the location of CD73, in proximity to adenosine receptor subtypes, indirectly determines its positive or negative effect in a variety of organs and tissues and that its action is affected by the transfer of nucleoside to subtype-specific adenosine receptors. Nonetheless, the bidirectional nature of CD73 as an emerging immune checkpoint in the pathogenesis of lung injury is still unknown. In this review, we explore the relationship between CD73 and the onset and progression of lung injury, highlighting the potential value of this molecule as a drug target for the treatment of pulmonary disease.

Evaluation of the efficacy and safety of percutaneous transforaminal endoscopic discectomy for multi-segmental lumbar disc herniation.

Objective: To investigate the clinical efficacy and safety of percutaneous transforaminal endoscopic discectomy (PTED) in the treatment of multi-segmental lumbar disc herniation (msLDH). Methods: From January 2021 to December 2021, 75 patients with msLDH admitted to Baoding No.1 Hospital of Traditional Chinese Medicine were selected and divided into PTED group (n=40) and posterior lumbar interbody fusion (PLIF) group (n=35) according to different surgical methods. The operative time, intraoperative blood loss, surgical complications, Oswestry disability index (ODI) and Japanese Orthopedic Association score (JOA) scores were compared between the two groups. Results: In the PTED group, the average operation time was 57.45±12.01minutes, and the average intraoperative blood loss was 50.57±16.69ml. There were three patients with surgical complications, including one case of hematoma, one case of aggravation of neurological symptoms and one case of new onset of neurological symptoms. In the PLIF group, there were 12 cases undergoing single-segment operation, 15 cases undergoing double-segment operation and 8 cases undergoing three-segment operation, the average operation time was 137.26±34.64minutes, and the average intraoperative blood loss was 456.06±33.06ml, there were four cases of wound fat liquefaction or delayed healing, two cases of hematoma, and three cases of exacerbation of original neurological symptoms or new neurological symptoms. At one month, six months, and one year of postoperative, the ODI and JOA scores of the two groups were significantly improved compared with those preoperative, and the ODI scores of the PTED group were better than those of the PLIF group (t=3.131, 2.263, 3.768, all P<0.05). Conclusion: The surgical effect of PTED in the treatment of LDH is similar to that of PLIF. However, PTED has the advantages of short operation time, less blood loss, fewer surgical complications, and high surgical safety. It is worthy of clinical promotion.

Research Progress in the Medical Application of Heavy Water, Especially in the Field of D2O-Raman Spectroscopy.

Heavy water is an ideal contrast agent for metabolic activity and can be adapted to a wide range of biological systems owing to its non-invasiveness, universal applicability, and cost-effectiveness. As a new type of probe, the heavy isotope of water has been widely used in the study of cell development, metabolism, tissue homeostasis, aging, and tumor heterogeneity. Herein, we review findings supporting the applications of and research on heavy water in monitoring of bacterial metabolism, rapid detection of drug sensitivity, identification of tumor cells, precision medicine, and evaluation of skin barrier function and promote the use of heavy water as a suitable marker for the development of detection and treatment methodologies.

The comprehensive analysis of clinical trials registration for IgA nephropathy therapy on ClinicalTrials.gov.

OBJECTIVES: IgA Nephropathy (IgAN) is common chronic kidney disease with a high incidence. This study aims to analyze comprehensively therapeutic clinical trials for IgAN registered on ClinicalTrials.gov. METHODS: Therapeutic trials for IgAN registered on ClinicalTrials.gov. up to 15 August 2021 were obtained. The general characteristics, features of experimental design, treatment strategies, and some main inclusion criteria and outcome measures were accessed. RESULTS: A total of 104 therapeutic clinical trials for IgAN were extracted on ClinicalTrials.gov up to 15 August 2021. Most of these trials explored the treatment for primary IgAN confirmed by renal biopsy in adults. Only 9% of all selected trials had results. Forty-five percent of trials recruited 50 or fewer participants, and 73% were adults or older adults. 99% of trials were interventional studies, and of all the interventional trials, 70% of trials were randomized, and 68% exercised a parallel assignment of intervention model. Immunosuppression was the most studied for the treatment of IgAN. Moreover, many novel agents had been increasingly studied in recent years. Furthermore, the inclusion criteria and primary outcome measures in these trials were diverse, and the level of proteinuria and change of proteinuria levels were the most used as inclusion criteria and primary outcome, respectively. CONCLUSIONS: The majority of therapeutic trials for IgAN were randomized, none masking and parallel-assignment interventional studies, primarily recruiting adult patients as research subjects. These trials had relatively small sample sizes and short observation. Thus, more large-scale, multicenter, and randomized controlled trials are still needed to improve the management for IgAN.

High, in Contrast to Low Levels of Acute Stress Induce Depressive-like Behavior by Involving Astrocytic, in Addition to Microglial P2X7 Receptors in the Rodent Hippocampus.

Extracellular adenosine 5'-triphosphate (ATP) in the brain is suggested to be an etiological factor of major depressive disorder (MDD). It has been assumed that stress-released ATP stimulates P2X7 receptors (Rs) at the microglia, thereby causing neuroinflammation; however, other central nervous system (CNS) cell types such as astrocytes also possess P2X7Rs. In order to elucidate the possible involvement of the MDD-relevant hippocampal astrocytes in the development of a depressive-like state, we used various behavioral tests (tail suspension test [TST], forced swim test [FST], restraint stress, inescapable foot shock, unpredictable chronic mild stress [UCMS]), as well as fluorescence immunohistochemistry, and patch-clamp electrophysiology in wild-type (WT) and genetically manipulated rodents. The TST and FST resulted in learned helplessness manifested as a prolongation of the immobility time, while inescapable foot shock caused lower sucrose consumption as a sign of anhedonia. We confirmed the participation of P2X7Rs in the development of the depressive-like behaviors in all forms of acute (TST, FST, foot shock) and chronic stress (UCMS) in the rodent models used. Further, pharmacological agonists and antagonists acted in a different manner in rats and mice due to their diverse potencies at the respective receptor orthologs. In hippocampal slices of mice and rats, only foot shock increased the current responses to locally applied dibenzoyl-ATP (Bz-ATP) in CA1 astrocytes; in contrast, TST and restraint depressed these responses. Following stressful stimuli, immunohistochemistry demonstrated an increased co-localization of P2X7Rs with a microglial marker, but no change in co-localization with an astroglial marker. Pharmacological damage to the microglia and astroglia has proven the significance of the microglia for mediating all types of depression-like behavioral reactions, while the astroglia participated only in reactions induced by strong stressors, such as foot shock. Because, in addition to acute stressors, their chronic counterparts induce a depressive-like state in rodents via P2X7R activation, we suggest that our data may have relevance for the etiology of MDD in humans.

[Identification of GeERF transcription factors in Gelsmium elegans and their expression under low temperature stress].

With prominent medicinal value, Gelsemium elegans has been overexploited, resulting in the reduction of the wild resource. As a result, artificial cultivation turns out to be a solution. However, this medicinal species is intolerant to low temperature, and thus genes responding to the low temperature are important for the cultivation of this species. Based on the transcriptome database of G. elegans at 4 ℃, 29 differentially expressed GeERF genes were identified. Bioinformatics analysis of 21 GeERF gene sequences with intact open reading frames showed that 12 and 9 of the GeERF proteins respectively clustered in DREB subgroup and ERF subgroup. GeDREB1 A-1-GeERF6 B-1, with molecular weight of 23.78-50.96 kDa and length of 212-459 aa, were all predicted to be hydrophilic and in nucleus. Furthermore, the full-length cDNA sequence of GeERF2B-1 was cloned from the leaves of G. elegans. Subcellular localization suggested that GeERF2B-1 was located in the nucleus. According to the quantitative reverse-transcription PCR(qRT-PCR), GeERF2B-1 showed constitutive expression in roots, stems, and leaves of G. elegans, and the expression was the highest in roots. In terms of the response to 4 ℃ treatment, the expression of GeERF2B-1 was significantly higher than that in the control and peaked at 12 h, suggesting a positive response to low temperature. This study lays a scientific basis for the functional study of GeERF transcription factors and provides gene resources for the improvement of stress resistance of G. elegans.

Surface-Exposed Single-Ni Atoms with Potential-Driven Dynamic Behaviors for Highly Efficient Electrocatalytic Oxygen Evolution.

Trapping the active sites on the exterior surface of hollow supports can reduce mass transfer resistance and enhance atomic utilization. Herein, we report a facile chemical vapor deposition strategy to synthesize single-Ni atoms decorated hollow S/N-doped football-like carbon spheres (Ni SAs@S/N-FCS). Specifically, the CdS@3-aminophenol/formaldehyde is carbonized into S/N-FCS. The gas-migrated Ni species are anchored on the surface of S/N-FCS simultaneously, yielding Ni SAs@S/N-FCS. The obtained catalyst exhibits outstanding performance for alkaline oxygen evolution reaction (OER) with an overpotential of 249 mV at 10 mA cm-2 , a small Tafel slope of 56.5 mV dec-1 , and ultra-long stability up to 166 hours without obvious fading. Moreover, the potential-driven dynamic behaviors of Ni-N4 sites and the contribution of the S dopant at different locations in the matrix to the OER activity are revealed by the operando X-ray absorption spectroscopy and theoretical calculations, respectively.

TCP and MADS-Box Transcription Factor Networks Regulate Heteromorphic Flower Type Identity in Gerbera hybrida.

The large sunflower family, Asteraceae, is characterized by compressed, flower-like inflorescences that may bear phenotypically distinct flower types. The CYCLOIDEA (CYC)/TEOSINTE BRANCHED1-like transcription factors (TFs) belonging to the TEOSINTE BRANCHED1/CYCLOIDEA/PROLIFERATING CELL FACTOR (TCP) protein family are known to regulate bilateral symmetry in single flowers. In Asteraceae, they function at the inflorescence level, and were recruited to define differential flower type identities. Here, we identified upstream regulators of GhCYC3, a gene that specifies ray flower identity at the flower head margin in the model plant Gerbera hybrida We discovered a previously unidentified expression domain and functional role for the paralogous CINCINNATA-like TCP proteins. They function upstream of GhCYC3 and affect the developmental delay of marginal ray primordia during their early ontogeny. At the level of single flowers, the Asteraceae CYC genes show a unique function in regulating the elongation of showy ventral ligules that play a major role in pollinator attraction. We discovered that during ligule development, the E class MADS-box TF GRCD5 activates GhCYC3 expression. We propose that the C class MADS-box TF GAGA1 contributes to stamen development upstream of GhCYC3 Our data demonstrate how interactions among and between the conserved floral regulators, TCP and MADS-box TFs, contribute to the evolution of the elaborate inflorescence architecture of Asteraceae.

Albumin-to-globulin ratio (AGR) as a potential marker of predicting lupus nephritis in Chinese patients with systemic lupus erythematosus.

OBJECTIVES: To evaluate a potential role of albumin-to-globulin ratio (AGR) in the development of lupus nephritis (LN) and determine the potential to use AGR as a marker for future LN in systemic lupus erythematosus (SLE) patients. METHODS: 194 newly diagnosed SLE patients without renal impairment were followed. The clinical data were collected and analyzed at the time of initial diagnosis of SLE and the end of follow-up. We compared baseline characteristics between those who did or did not develop LN on follow-up. Univariate and multivariate Cox hazard analysis were used to identify predictors of lupus nephritis. RESULTS: Among the 194 newly diagnosed SLE patients without renal impairment, 26 (13.40%) patients were diagnosed with LN during a median follow-up of 53.87 months. On univariate Cox analysis, patients with the history of alopecia, higher SBP, lower AGR, lower CRP, lower C3, lower C4, higher anti-dsDNA Ab, presence of ANA homogeneous patterns or higher SLEDAI had an increased probability of developing LN. In a multivariate model, the history of alopecia (adjust hazard ratio, aHR = 3.614, 95%CI 1.365-9.571 P = 0.010), lower AGR (aHR = 6.968, 95%CI 1.873-25.919, P = 0.004), lower CRP (aHR = 4.230, 95%CI 1.591-11.247, P = 0.004) and higher level of anti-dsDNA (aHR = 2.675, 95%CI 1.008-7.093, P = 0.048) were independently associated with an increased risk of developing LN after adjusting for covariates. CONCLUSION: Our findings indicated that SLE patients with low AGR, low CRP, high anti-dsDNA and the history of alopecia were more likely to develop LN in the course of SLE. AGR shown the greatest hazard for developing LN among them, it may be a strong predictor.

Influence of hydrotrope on solubility and bioavailability of curcumin: its complex formation and solid-state characterization.

In this study, meglumine (Meg) and arginine (Arg), acting as the hydrotrope, were used to form the stable curcumin (Cur)-hydrotrope complexes, respectively. Based on the single factor experiment optimization, the Cur-Meg/or Cur-Arg complex was prepared and then characterized by Fourier transform infrared spectroscopy (FTIR), X-ray powder diffraction (XRD), and differential scanning calorimetry (DSC). The results showed that Cur-Meg/Arg complexes bound together by hydrogen bonds/or ionic bonds were successfully prepared and the amorphous state of Cur appeared in their complexes. Compared with the Cur-Meg complex, Cur-Arg had better stability in stress testing. Cur-Meg/Arg complexes had a faster drug release rate in vitro and the area-under-curve (AUC) of Cur-Meg/Arg solutions in rats were at least 6.3-fold larger than that of the Cur suspensions. These findings suggest that hydrotropy combined with solid dispersion technique is a simple and effective way to improve the bioavailability of Cur.HIGHLIGHTSThe optimal Cur-Meg/or Cur-Arg complex powder was prepared and characterized.The Cur release rate in vitro was significantly improved.The bioavailability can be improved when using Cur-Meg/or Cur-Arg complex.A simple and effective way to improve the bioavailability of Cur.

Cation-Exchange Induced Precise Regulation of Single Copper Site Triggers Room-Temperature Oxidation of Benzene.

The controllable synthesis of stable single-metal site catalysts with an expected coordination environment for high catalytic activity and selectivity is still challenging. Here, we propose a cation-exchange strategy for precise production of an edge-rich sulfur (S) and nitrogen (N) dual-decorated single-metal (M) site catalysts (M = Cu, Pt, Pd, etc.) library. Our strategy relies on the anionic frameworks of sulfides and N-rich polymer shell to generate abundant S and N defects during high-temperature annealing, further facilitating the stabilization of exchanged metal species with atomic dispersion and excellent accessibility. This process was traced by in situ transmission electron microscopy, during which no metal aggregates were observed. Both experiments and theoretical results reveal the precisely obtained S, N dual-decorated Cu sites exhibit a high activity and low reaction energy barrier in catalytic hydroxylation of benzene at room temperature. These findings provide a route to controllably produce stable single-metal site catalysts and an engineering approach for regulating the central metal to improve catalytic performance.

Single Iron Site Nanozyme for Ultrasensitive Glucose Detection.

Nanomaterials with enzyme-mimicking characteristics have engaged great awareness in various fields owing to their comparative low cost, high stability, and large-scale preparation. However, the wide application of nanozymes is seriously restricted by the relatively low catalytic activity and poor specificity, primarily because of the inhomogeneous catalytic sites and unclear catalytic mechanisms. Herein, a support-sacrificed strategy is demonstrated to prepare a single iron site nanozyme (Fe SSN) dispersed on the porous N-doped carbon. With well-defined coordination structure and high density of active sites, the Fe SSN performs prominent peroxidase-like activity by efficiently activating H2 O2 into hydroxyl radical (•OH) species. Furthermore, the Fe SSN is applied in colorimetric detection of glucose through a multienzyme biocatalytic cascade platform. Moreover, a low-cost integrated agarose-based hydrogel colorimetric biosensor is designed and successfully achieves the visualization evaluation and quantitative detection of glucose. This work expands the application of single-site catalysts in the fields of nanozyme-based biosensors and personal biomedical diagnosis.

Transcription Factor bHLH2 Represses CYSTEINE PROTEASE77 to Negatively Regulate Nodule Senescence.

Legume-rhizobia symbiosis is a time-limited process due to the onset of senescence, which results in the degradation of host plant cells and symbiosomes. A number of transcription factors, proteases, and functional genes have been associated with nodule senescence; however, whether other proteases or transcription factors are involved in nodule senescence remains poorly understood. In this study, we identified an early nodule senescence mutant in Medicago truncatula, denoted basic helix-loop-helix transcription factor2 (bhlh2), that exhibits decreased nitrogenase activity, acceleration of plant programmed cell death (PCD), and accumulation of reactive oxygen species (ROS). The results suggest that MtbHLH2 plays a negative role in nodule senescence. Nodules of wild-type and bhlh2-TALEN mutant plants at 28 d postinoculation were used for transcriptome sequencing. The transcriptome data analysis identified a papain-like Cys protease gene, denoted MtCP77, that could serve as a potential target of MtbHLH2. Electrophoretic mobility shift assays and chromatin immunoprecipitation analysis demonstrated that MtbHLH2 directly binds to the promoter of MtCP77 to inhibit its expression. MtCP77 positively regulates nodule senescence by accelerating plant PCD and ROS accumulation. In addition, the expression of MtbHLH2 in the nodules gradually decreased from the meristematic zone to the nitrogen fixation zone, whereas the expression of MtCP77 showed enhancement. These results indicate that MtbHLH2 and MtCP77 have opposite functions in the regulation of nodule senescence. These results reveal significant roles for MtbHLH2 and MtCP77 in plant PCD, ROS accumulation, and nodule senescence, and improve our understanding of the regulation of the nodule senescence process.