Solar CO2 Reduction Enabled by Cascade Hole Migration.

Solar-powered photocatalytic conversion of CO2 to hydrocarbon fuels represents an emerging approach to solving the greenhouse effect. However, low charge separation efficiency, deficiency of surface catalytic active sites, and sluggish charge-transfer kinetics, together with the complicated reaction pathway, concurrently hinder the CO2 reduction. Herein, we show the rational construction of transition metal chalcogenides (TMCs) heterostructure CO2 reduction photosystems, wherein the TMC substrate is tightly integrated with amorphous oxygen-containing cobalt sulfide (CoSOH) by a solid non-conjugated polymer, i.e., poly(vinyl alcohol) (PVA), to customize the unidirectional charge-transfer pathway. In this well-defined multilayered nanoarchitecture, the PVA interim layer intercalated between TMCs and CoSOH acts as a hole-relaying mediator and meanwhile boosts CO2 adsorption capacity, while CoSOH functions as a terminal hole-collecting reservoir, stimulating the charge transport kinetics and boosting the charge separation over TMCs. This peculiar interface configuration and charge transport characteristics endow TMC/PVA/CoSOH heterostructures with significantly enhanced visible-light-driven photoactivity and CO2 conversion. Based on the intermediates probed during the photocatalytic CO2 reduction reaction, the photocatalytic mechanism was determined. Our work would inspire sparkling ideas to mediate the charge transfer over semiconductor for solar carbon neutral conversion.

Self-Transformation of Atomically Precise Alloy Nanoclusters to Plasmonic Alloy Nanocrystals: Evaluating Photosensitization in Solar Water Oxidation.

Atomically precise alloy nanoclusters (NCs) inherit the advantages of homometal NC counterparts such as atomic stacking fashion, quantum confinement effect, and enriched catalytic active sites and simultaneously possess the advantageous physicochemical properties such as significantly enhanced photostability, ideal photosensitization efficiency, and favorable energy band structure. Nevertheless, elucidation of the roles of alloy NCs and alloy nanocrystals (NYs) in boosting solar water oxidation has so far not yet been reported owing to the deficiency of applicable alloy NC photosystems. Herein, utilizing the generic thermal-induced self-transformation of alloy NCs to alloy NYs, we comprehensively explore the photosensitization properties of glutathione (GSH)-capped alloy NCs (AgxAu1-x@GSH and CuxAu1-x@GSH) and the corresponding alloy NY (AgAu and CuAu) counterparts in solar water oxidation reaction. The results imply that photoelectrons of alloy NCs surpass the hot electrons over plasmonic alloy NYs in stimulating the PEC water oxidation reaction. The photoelectrons of alloy NCs demonstrate lower interfacial charge-transfer resistance, longer carrier lifetime, and a more enhanced photosensitization effect with respect to the plasmonic alloy NYs, contributing to the significantly boosted photoelectrochemical water oxidation activities. Moreover, we found that our result is universal.

Maneuvering the Directional Charge Flow for Photoredox Organic Conversion.

Transition-metal chalcogenide quantum dots (TMC QDs) show great promise in artificial photosynthesis for excellent light-harvesting capability. Nonetheless, TMC QDs have limitations of ultrafast charge recombination rate, sluggish carrier migration kinetics, and generic photocorrosion, retarding their widespread applications. To solve these obstacles, herein, we demonstrate the stimulation of charge migration over TMC QDs with the aid of nonconjugated insulating polymer and graphene (GR) for a versatile photoredox selective organic transformation. To this end, an ultrathin insulating polymer layer, i.e., poly(allylamine hydrochloride) (PAH), grafted on the GR framework, is electrostatically intercalated at the interface of TMCs QDs and the GR framework via a self-assembly for constructing TMC QDs/PAH/GR three-dimensional spatially multilayered heterostructures. In this well-defined nanoarchitecture, TMC QDs function as a light-harvesting antenna, GR as a terminal electron reservoir, and PAH as an intermediate interfacial charge relay mediator. We ascertain that the ultrathin PAH interim layer unexpectedly fosters the photoelectron migration from TMCs QDs to the GR framework in a tunable fashion, boosting the charge separation of TMCs QDs and resulting in significantly improved photoactivities toward anaerobic reduction of aromatic nitro compounds to amino derivatives and oxidation of alcohols to aldehydes under visible light. Photoredox catalysis mechanisms of such TMC QDs/PAH/GR photosystems are elucidated, and the active species in these photoredox organic conversion reactions are comprehensively determined. Our work would open new frontiers to finely modulate the charge transport of TMCs QDs via nonconjugated insulating polymers for solar energy conversion.

A single-center, randomized, controlled study on the efficacy of niacinamide-containing body emollients combined with cleansing gel in the treatment of mild atopic dermatitis.

OBJECTIVE: To observe the effect of niacinamide-containing body emollients combined with a cleansing gel on the clinical symptoms of mild atopic dermatitis (AD) in adults. METHODS: From July 2022 to January 2023, adults with mild AD were enrolled at Huashan Hospital Affiliated to Fudan University using single-center, randomized and placebo-controlled methods. They were divided into three groups: the control group, treatment group 1 (T1) receiving niacinamide-containing body emollients alone, and treatment group 2 (T2) receiving emollients plus niacinamide-containing cleansing gel. All patients were orally administered 10 mg of ebastine tablets daily. AD severity (SCORAD score), peak pruritus numeric rating scale (PP-NRS), patient-oriented measure of eczema (POEM), dermatological quality of life index (DLQI) score, transepidermal water loss (TEWL), and stratum corneum water content (SCWC) were measured by the same dermatologist at days 0, 7, 14, and 28. RESULTS: A total of 122 patients were enrolled, including 38 in the control group, 42 in the T1 group and 42 in the T2 group. There were no obvious adverse reactions at the end of the study and the clinical scores and stratum corneum barrier of all the groups improved significantly relative to baseline. The SCORAD, PP-NRS, DLQI, TEWL and SCWC scores in T1 group (12.43 ± 3, 3.3 ± 0.9, 7.1 ± 2.33, 17.1 ± 9.12, 67.2 ± 21.46, seperately) and T2 group (11.17 ± 3.26, 3 ± 1.3, 6.5 ± 2.11, 16.3 ± 9.12, 69.4 ± 24.52, seperately) were significantly improved than the control group(15.1 ± 3.64, 4.3 ± 1.7, 9.5 ± 2.46, 21.2 ± 9.47, 52.7 ± 22.43, seperately) at the endpoint of the study, while compared the POEM scores, only T2 group showed the difference with control group (5.2 ± 1.4 vs. 6 ± 1.6). The epidermal barrier parameters of TEWL and SCWC in the T2 group (17.57 ± 5.24, 66.46 ± 21.38, seperately) were significantly better than that of the T1 (19.96 ± 4.45, 56.45 ± 20.48, seperately) and control group(21.89 ± 7.03, 51.56 ± 16.58, seperately) on the 14th day of follow-up. CONCLUSION: The use of niacinamide-containing body emollients can significantly improve the clinical symptoms, quality of life, and skin barrier function in patients with mild AD. The addition of niacinamide-containing cleansing gel can also affect the clinical efficacy at certain time points.

Salvianolic acid B ameliorates retinal deficits in an early-stage Alzheimer's disease mouse model through downregulating BACE1 and Aß generation.

Alzheimer's disease (AD) is a neurodegenerative disease with subtle onset, early diagnosis remains challenging. Accumulating evidence suggests that the emergence of retinal damage in AD precedes cognitive impairment, and may serve as a critical indicator for early diagnosis and disease progression. Salvianolic acid B (Sal B), a bioactive compound isolated from the traditional Chinese medicinal herb Salvia miltiorrhiza, has been shown promise in treating neurodegenerative diseases, such as AD and Parkinson's disease. In this study we investigated the therapeutic effects of Sal B on retinopathy in early-stage AD. One-month-old transgenic mice carrying five familial AD mutations (5×FAD) were treated with Sal B (20 mg·kg-1·d-1, i.g.) for 3 months. At the end of treatment, retinal function and structure were assessed, cognitive function was evaluated in Morris water maze test. We showed that 4-month-old 5×FAD mice displayed distinct structural and functional deficits in the retinas, which were significantly ameliorated by Sal B treatment. In contrast, untreated, 4-month-old 5×FAD mice did not exhibit cognitive impairment compared to wild-type mice. In SH-SY5Y-APP751 cells, we demonstrated that Sal B (10 µM) significantly decreased BACE1 expression and sorting into the Golgi apparatus, thereby reducing Aß generation by inhibiting the ß-cleavage of APP. Moreover, we found that Sal B effectively attenuated microglial activation and the associated inflammatory cytokine release induced by Aß plaque deposition in the retinas of 5×FAD mice. Taken together, our results demonstrate that functional impairments in the retina occur before cognitive decline, suggesting that the retina is a valuable reference for early diagnosis of AD. Sal B ameliorates retinal deficits by regulating APP processing and Aß generation in early AD, which is a potential therapeutic intervention for early AD treatment.

Amelioration of olfactory dysfunction in a mouse model of Parkinson's disease via enhancing GABAergic signaling.

BACKGROUND: Olfactory dysfunction is among the earliest non-motor symptoms of Parkinson's disease (PD). As the foremost pathological hallmark, α-synuclein initiates the pathology in the olfactory pathway at the early stage of PD, particularly in the olfactory epithelium (OE) and olfactory bulb (OB). However, the local neural microcircuit mechanisms underlying olfactory dysfunction between OE and OB in early PD remain unknown. RESULTS: We observed that odor detection and discrimination were impaired in 6-month-old SNCA-A53T mice, while their motor ability remained unaffected. It was confirmed that α-synuclein increased and accumulated in OB but not in OE. Notably, the hyperactivity of mitral/tufted cells and the excitation/inhibition imbalance in OB were found in 6-month-old SNCA-A53T mice, which was attributed to the impaired GABAergic transmission and aberrant expression of GABA transporter 1 and vesicular GABA transporter in OB. We further showed that tiagabine, a potent and selective GABA reuptake inhibitor, could reverse the impaired olfactory function and GABAergic signaling in OB of SNCA-A53T mice. CONCLUSIONS: Taken together, our findings demonstrate potential synaptic mechanisms of local neural microcircuit underlying olfactory dysfunction at the early stage of PD. These results highlight the critical role of aberrant GABAergic signaling of OB in early diagnosis and provide a potential therapeutic strategy for early-stage PD.

Effect of Several Naja atra Antivenom Injection Methods on the Rabbit Model of Naja naja atra Bite Poisoning.

Snakebite is a global public health concern, which often occurs in tropical and subtropical underdeveloped areas, but it is often neglected. In the southern China, Naja naja atra (Chinese cobra) is a common venomous snake that causes swelling and necrosis of local tissues, even amputation and death. Currently, the main therapy is the administration of Naja atra antivenom, which greatly reduces mortality. However, the antivenom is not particularly effective in the improvement of local tissue necrosis. Clinically, antivenom is mainly administered intravenously. We speculated that the method of injection influences the efficacy of antivenom. In this study, the rabbit model was used to explore the effects of different antivenom injection methods on systemic and local poisoning symptoms. If topical injection of antivenom contributes to ameliorate tissue necrosis, then we need to reconsider the use of Naja atra antivenom.

The lncRNA Malat1 functions as a ceRNA to contribute to berberine-mediated inhibition of HMGB1 by sponging miR-181c-5p in poststroke inflammation.

Long non-coding RNAs (lncRNAs) have been identified as essential mediators in neurological dysfunction. Our previous study shows that berberine (BBR) hampers the nuclear-to-cytosolic translocation of high-mobility group box 1 (HMGB1) in the process of poststroke inflammation. In this study, we explored the role of lncRNA metastasis-associated lung adenocarcinoma transcript 1 (Malat1) in the process of BBR-induced inhibition of HMGB1 in ischemic brain. Before the 60-min MCAO surgery, the mice were pretreated with BBR (50 mg· kg-1 per day, ig) for 14 days or ICV injected with specific lentiviral vector or shRNA. We showed that MCAO caused marked increase in the expression Malat1 and HMGB1 in the ipsilateral cortex, which was significantly attenuated by pretreatment with BBR. Knockdown of Malat1 attenuated the inflammatory injury after brain ischemia, whereas overexpression of Malat1 exacerbated ischemic brain inflammation. Overexpression of Malat1 also reversed BBR-induced reduction of HMGB1 and proinflammatory cytokines. The above results suggested a potential correlation between Malat1 and stroke inflammation. Based on informatics analysis we predicted that HMGB1 was a direct downstream target of miR-181c-5p, whereas Malat1 acted as a competitive endogenous RNA (ceRNA) for miR-181c-5p targeted the 3'-UTR of HMGB1 to promote inflammation after ischemic stroke. Knockdown of Malat1 significantly decreased HMGB1 level, which could be abrogated by transfection with miR-181c-5p inhibitors. Taken together, our results demonstrate for the first time that Malat1/miR-181c-5p/HMGB1 axis may be a key pathway of BBR-induced antiinflammation effects in stroke, and they may provide a novel avenue for targeted therapy.

Berberine attenuates ischemia-reperfusion injury through inhibiting HMGB1 release and NF-κB nuclear translocation.

Inflammatory damage plays an important role in cerebral ischemic pathogenesis and represents a new target for treatment of stroke. Berberine is a natural medicine with multiple beneficial biological activities. In this study, we explored the mechanisms underlying the neuroprotective action of berberine in mice subjected transient middle cerebral artery occlusion (tMCAO). Male mice were administered berberine (25, 50 mg/kg/d, intragastric; i.g.), glycyrrhizin (50 mg/kg/d, intraperitoneal), or berberine (50 mg/kg/d, i.g.) plus glycyrrhizin (50 mg/kg/d, intraperitoneal) for 14 consecutive days before tMCAO. The neurological deficit scores were evaluated at 24 h after tMCAO, and then the mice were killed to obtain the brain samples. We showed that pretreatment with berberine dose-dependently decreased the infarct size, neurological deficits, hispathological changes, brain edema, and inflammatory mediators in serum and ischemic cortical tissue. We revealed that pretreatment with berberine significantly enhanced uptake of 18F-fluorodeoxyglucose of ischemic hemisphere comparing with the vehicle group at 24 h after stroke. Furthermore, pretreatment with berberine dose-dependently suppressed the nuclear-to cytosolic translocation of high-mobility group box1 (HMGB1) protein, the cytosolic-to nuclear translocation of nuclear factor kappa B (NF-κB) and decreased the expression of TLR4 in ischemic cortical tissue. Moreover, co-administration of glycyrrhizin and berberine exerted more potent suppression on the HMGB1/TLR4/NF-κB pathway than berberine or glycyrrhizin administered alone. These results demonstrate that berberine protects the brain from ischemia-reperfusion injury and the mechanism may rely on its anti-inflammatory effects mediated by suppressing the activation of HMGB1/TLR4/NF-κB signaling.

Development of a novel individualized warfarin dose algorithm based on a population pharmacokinetic model with improved prediction accuracy for Chinese patients after heart valve replacement.

The gene-guided dosing strategy of warfarin generally leads to over-dose in patients at doses lower than 2 mg/kg, and only 50% of individual variability in daily stable doses can be explained. In this study, we developed a novel population pharmacokinetic (PK) model based on a warfarin dose algorithm for Han Chinese patients with valve replacement for improving the dose prediction accuracy, especially in patients with low doses. The individual pharmacokinetic (PK) parameter - apparent clearance of S- and R-warfarin (CLs) was obtained after establishing and validating the population PK model from 296 recruited patients with valve replacement. Then, the individual estimation of CLs, VKORC1 genotypes, the steady-state international normalized ratio (INR) values and age were used to describe the maintenance doses by multiple linear regression for 144 steady-state patients. The newly established dosing algorithm was then validated in an independent group of 42 patients and was compared with other dosing algorithms for the accuracy and precision of prediction. The final regression model developed was as follows: Dose=-0.023×AGE+1.834×VKORC1+0.952×INR+2.156×CLs (the target INR value ranges from 1.8 to 2.5). The validation of the algorithm in another group of 42 patients showed that the individual variation rate (71.6%) was higher than in the gene-guided dosing models. The over-estimation rate in patients with low doses (<2 mg/kg) was lower than the other dosing methods. This novel dosing algorithm based on a population PK model improves the predictive performance of the maintenance dose of warfarin, especially for low dose (<2 mg/d) patients.

Self-assembled structures and excellent surface properties of a novel anionic phosphate diester surfactant derived from natural rosin acids.

A novel anionic rosin-based phosphate diester sodium (DDPDS) was successfully synthesized from raw dehydroabietic acid, a natural raw material, via four-step reactions: acylation, esterification, phosphorylation and neutralization. Nuclear magnetic resonance (13C NMR) and Fourier transform infrared spectroscopy (FT-IR) were used to characterize the structure of target products. The aggregation behaviors in aqueous-ethanol solution and surface properties of DDPDS and its mixed systems were investigated by transmission electron microscopy (TEM), automatic tensiometer and contact angle measuring instrument. The results showed that DDPDS had high surface activity, unexpected emulsification and excellent wettability. The critical micelle concentration (CMC) of 1.35g∗L-1, the minimum surface tension (γcmc) of 31.75mN∗m-1, emulsifying power of 153s and the minimum contact angle of 13.4° were determined for DDPDS. Spherical vesicles with diameter about 50nm and 5µm were self-assembled respectively in aqueous-ethanol solution when DDPDS concentration is about 1 CMC and 5 CMC. Two surfactant ionic self-assembly systems were constructed by mixing DDPDS with sodium dodecylbenzenesulfonate (SDBS) and cetyltrimethylammonium bromide (CTAB), which forms 40nm and 20nm spherical micelles in 1 CMC aqueous-ethanol solution. Possible formation mechanisms of surfactant ionic self-assembly systems on a combination of ionic interactions between DDPDS and SDBS or CTAB are discussed. It was found that there were an obvious synergistic effect of foam stability in DDPDS/SDBS mixed system and an obvious synergistic effect of foam capability in DDPDS/CTAB mixed system.

Effects of the multidrug resistance modulator HZ08 on the apoptosis pathway in human chronic leukaemia cell line K562/A02.

oancer falls to respond to chemotherapy by acquiring multidrug resistance in over 90% of patients. A previous study revealed that multidrug resistance modulator HZ08 had great multidrug resistance reversal effect in vitro and in vivo. It could enhance adriamycin (doxorubicin) induced intrinsic apoptosis pathway and rectify cell cycle and some apoptosis related proteins in human breast resistant cancer MCF-7/ADM cells. This study detected Rh123 accumulation to assess the effect of HZ08 on P-glycoprotein function in human chronic leukaemia cell line K562/A02. Moreover, mitochondria membrane potential, cytochrome c release and caspase-3 activity were analyzed for HZ08 treatment with or without vincristine. Since pretreatment with HZ08 could also reverse the multidrug resistance to vincristine in K562/A02 cells, the individual influence of HZ08 was further detected on apoptotic regulator like Bcl-2, Bax, p53, cell cycle checkpoints and proliferation regulatory factors like survivin, hTERT, c-Myc, c-Fos, c-Jun. Finally, it revealed that HZ08 increased vincristine induced activation in intrinsic apoptosis pathway by inhibition of P-gp mediated efflux. In addition, the outstanding reversal effect of HZ08 should also attribute to its individual effect on apoptosis and proliferation related regulatory factors. It renders HZ08 possibility of application in pretreatment to reverse multidrug resistance while avoiding unexpected drug interactions and accumulative toxicity.

Protective effects of ginsenoside Rb(3) on oxygen and glucose deprivation-induced ischemic injury in PC12 cells.

AIM: To investigate the protective effects of ginsenoside Rb(3), a triterpenoid saponin isolated from the leaves of Panax notoginseng, on ischemic and reperfusion injury model of PC12 cells and elucidate the related mechanisms. METHODS: PC12 cells exposed to oxygen and glucose deprivation (OGD) and restoration (OGD-Rep) were used as an in vitro model of ischemia and reperfusion. 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay and lactate dehydrogenase (LDH) leakage were used to evaluate the protective effects of ginsenoside Rb(3). Cellular apoptosis and mitochondrial membrane potential (MMP) were analyzed using flow cytometry. Intracellular calcium ion concentration ([Ca(2+)](i)) was detected using fluorophotometer system. Caspase-3, -8, and -9 activities were measured using assay kits with an ELISA reader. Western blotting assay was used to evaluate the release of cytochrome c and expression of caspase-3, Bcl-2 and Bax proteins. RESULTS: It was shown that ginsenoside Rb(3) (0.1-10 micromol/L) significantly increased cell viability and inhibited LDH release in a dose-dependent manner on the ischemic model. In addition, ginsenoside Rb(3) also significantly inhibited ischemic injury-induced apoptosis, [Ca(2+)](i) elevation, and decrease of MMP. Meanwhile, pretreatment with ginsenoside Rb(3) significantly induced an increase of Bcl-2 protein expression and a decrease of cytosolic cytochrome c, cleaved-caspase 3 and Bax protein expression, the caspase-3, -8, and -9 activity were also inhibited. CONCLUSION: The results indicated that ginsenoside Rb(3) could markedly protected OGD-Rep induced ischemic injury and the mechanisms maybe related to its suppression of the intracellular Ca(2+) elevation and inhibition of apoptosis and caspase activity. Ginsenoside Rb(3) could be a promising candidate in the development of a novel class of anti-ischemic agent.