Navigating the landscape of enzyme design: from molecular simulations to machine learning.

Global environmental issues and sustainable development call for new technologies for fine chemical synthesis and waste valorization. Biocatalysis has attracted great attention as the alternative to the traditional organic synthesis. However, it is challenging to navigate the vast sequence space to identify those proteins with admirable biocatalytic functions. The recent development of deep-learning based structure prediction methods such as AlphaFold2 reinforced by different computational simulations or multiscale calculations has largely expanded the 3D structure databases and enabled structure-based design. While structure-based approaches shed light on site-specific enzyme engineering, they are not suitable for large-scale screening of potential biocatalysts. Effective utilization of big data using machine learning techniques opens up a new era for accelerated predictions. Here, we review the approaches and applications of structure-based and machine-learning guided enzyme design. We also provide our view on the challenges and perspectives on effectively employing enzyme design approaches integrating traditional molecular simulations and machine learning, and the importance of database construction and algorithm development in attaining predictive ML models to explore the sequence fitness landscape for the design of admirable biocatalysts.

Preparation and properties of oxidized multi-walled carbon nanotube superhydrophobic composites modified by bio-fatty acids.

In this paper, a preparation method of superhydrophobic composites of oxidized multi-walled carbon nanotubes modified by stearic acid (SA) is proposed. Hydroxylated multi-walled carbon nanotubes (HMWCNTs) were obtained by oxidizing multi-walled carbon nanotubes with potassium dichromate to give them hydroxyl groups on the surface. Subsequently, the carboxyl group in the SA molecule was esterified with the hydroxyl group on the HMWCNTs. SA molecules were grafted onto the surface of multi-walled carbon nanotubes. SA modified oxidized multi-walled carbon nanotubes (SMWCNT) superhydrophobic composites were obtained. The results show that the water contact angle (WCA) of superhydrophobic composites can reach up to 174°. At the same time, the modified nanocomposites have good anti-icing and corrosion resistance. After low temperature delayed freezing test, the freezing extension time of the nanocomposite film is 30 times that of the smooth surface. Under strong acid and alkali conditions, the superhydrophobic nanocomposites still maintain good superhydrophobicity. The nanocomposites may have potential applications in the preparation of large-scale superhydrophobic coatings.

Enzyme/ROS dual-sensitive nanoplatform with on-demand Celastrol release capacity for enhanced ulcerative colitis therapy by ROS scavenging, microbiota rebalancing, inflammation alleviating.

BACKGROUND: The oral administration of drugs for treating ulcerative colitis (UC) is hindered by several factors, including inadequate gastrointestinal stability, insufficient accumulation in colonic lesions, and uncontrolled drug release. METHODS: A multiple sensitive nano-delivery system comprising ß-cyclodextrin (CD) and 4-(hydroxymethyl)phenylboronic acid (PAPE) with enzyme/reactive oxygen species (ROS) sensitivity was developed to load celastrol (Cel) as a comprehensive treatment for UC. RESULTS: Owing to the positive charge in the site of inflamed colonic mucosa, the negatively charged nanomedicine (Cel/NPs) could efficiently accumulate. Expectedly, Cel/NPs showed excellent localization ability to colon in vitro and in vivo tests. The elevated concentration of ROS and intestinal enzymes in the colon microenvironment quickly break the CD, resulting in Cel release partially to rebalance microbiota and recover the intestinal barrier. The accompanying cellular internalization of residual Cel/NPs, along with the high concentration of cellular ROS to trigger Cel burst release, could decrease the expression of inflammatory cytokines, inhibit colonic cell apoptosis, promote the macrophage polarization, scavenge ROS, and regulate the TLR4/NF-κB signaling pathway, which certified that Cel/NPs possessed a notably anti-UC therapy outcome. CONCLUSIONS: We provide a promising strategy for addressing UC symptoms via an enzyme/ROS-sensitive oral platform capable of releasing drugs on demand.

Optimal assessment of the glomerular filtration rate in older chinese patients using the equations of the Berlin Initiative Study.

AIM: To evaluate the performances of the various estimated glomerular filtration rate (eGFR) equations of the Chronic Kidney Disease Epidemiology Collaboration, the Berlin Initiative Study (BIS), and the Full Age Spectrum (FAS) in older Chinese. METHODS: This study enrolled Chinese adults aged ≥ 65 years who underwent GFR measurements (via 99Tcm-DTPA renal dynamic imaging) in our hospital from 2011 to 2022. Using the measured glomerular filtration rate (mGFR) as the reference, we derived the bias, precision, accuracy, and consistency of each equation. RESULTS: We enrolled 519 participants, comprising 155 with mGFR ≥ 60 mL/min/1.73 m2 and 364 with mGFR < 60 mL/min/1.73 m2. In the total patients, the BIS equation based on creatinine and cystatin C (BIScr-cys) exhibited the lowest bias [median (95% confidence interval): 1.61 (0.77-2.18)], highest precision [interquartile range 11.82 (10.32-13.70)], highest accuracy (P30: 81.12%), and best consistency (95% limit of agreement: 101.5 mL/min/1.73 m2). In the mGFR ≥ 60 mL/min/1.73 m2 subgroup, the BIScr-cys and FAS equation based on creatinine and cystatin C (FAScr-cys) performed better than the other equations; in the mGFR < 60 mL/min/1.73 m2 subgroup, all equations exhibited relatively large deviations from the mGFR. Of all eight equations, the BIScr-cys performed the best. CONCLUSIONS: Although no equation was fully accurate in the mGFR < 60 mL/min/1.73 m2 subgroup, the BIScr-cys (of the eight equations) assessed the eGFRs of the entire population best. A new equation is urgently required for older Chinese and even East Asians, especially those with moderate-to-severe renal insufficiency.

The percentage of controlled chronic rhinosinusitis after treatment: a systematic review and meta-analysis.

PURPOSE: Chronic rhinosinusitis (CRS) is a chronic disease with a high recurrence rate, and the aim of treating CRS is to maintain disease control. Recently, a series of CRS control instruments have been developed to assess the control levels. We pooled existing studies to evaluate the percentage of controlled CRS after treatment in patients with CRS. METHODS: A systematic literature review and meta-analysis using PubMed, Google Scholar, Scopus, and Cochrane databases was conducted to identify studies assessing CRS control. Both comprehensive assessments and self-report of CRS control were included. RESULTS: 9 studies with 1931 patients after treatment and 295 patients before treatment were included. CRS control assessments of the 2012 European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS 2012), EPOS 2020, and Sinus Control Test (SCT) were comprehensive assessments utilized in the clinic practice. The self-report assessment included patient-reported global level of CRS control. These existing disease control instruments categorized patients into three (uncontrolled, partly controlled, and controlled) or five (not at all, a little, somewhat, very, and completely) control categories. Only 8% (95% CI 0.05-0.11) of patients with CRS stayed well controlled before treatment assessed by comprehensive assessments. About 35% (95% CI 0.22-0.49) of patients achieved well controlled after treatment when assessed by the comprehensive measures. Meanwhile, 40% (95% CI 0.28-0.52) of patients reported well controlled after treatment when using self-report. CONCLUSION: About 35-40% of patients with CRS showed well controlled after treatment, which stressed the importance of identifying these undertreated patients with CRS.

Contributions of the bacterial communities to the microcystin degradation and nutrient transformations during aerobic composting of algal sludge.

Aerobic composting is a useful method for managing and disposing of salvaged algal sludge. To optimize the composting process and improve compost quality, it is necessary to understand the functions and responses of microbial communities therein. This work studied the degradation process of organic matter and the assemblage of bacterial communities in algal sludge composting via 16S rRNA amplicon sequencing. The results showed that 77.08% of the microcystin was degraded during the thermophilic stage of composting, which was the main period for microcystin degradation. Bacterial community composition and diversity changed significantly during the composting, and gradually stabilized as the compost matured. Different composting stages may be dominated by different module groups separately, as shown in the co-occurrence networks of composting bacterial communities. In the networks, all bacteria associated with microcystin degradation were identified as connectors between different module groups. The algal sludge composting process was driven primarily by deterministic processes, and the main driving forces for bacterial community assembly were temperature, dissolved organic carbon, ammonium, and microcystin. At last, by applying the structural equation modeling method, the bacterial communities under influences of physiochemical properties were proved as the main mediators for the microcystin degradation. This study provides valuable insights into the optimization of bacterial communities in composting to improve the efficiency of microcystin degradation and the quality of the compost product.

Preparation and Anti-Icing Properties of Zirconia Superhydrophobic Coating.

Zirconia (ZrO2) is a ceramic material with high-temperature resistance and good insulating properties. Herein, for the first time, the surface of ZrO2 was modified with docosanoic acid (DCA) to improve its self-cleaning and hydrophobic properties. This surface modification transformed the surface of ZrO2 from hydrophilic to superhydrophobic. A two-step spraying method was used to prepare the superhydrophobic surface of ZrO2 by sequentially applying a primer and a topcoat. The primer was a solution configured using an epoxy resin as the adhesive and polyamide as the curing agent, while the topcoat was a modified ZrO2 solution. The superhydrophobic surface of ZrO2 exhibited a contact angle of 154° and a sliding angle of 4°. Scanning electron microscopy, X-ray diffraction, energy-dispersive X-ray spectroscopy, thermogravimetric analysis, and other analytical techniques were used to characterize the prepared zirconia particles and their surfaces. Moreover, results from surface self-cleaning and droplet freezing tests showed that DCA-modified ZrO2 can be well combined, and its coatings show good self-cleaning and anti-icing properties on TA2 bases.

ALDH2 ameliorates ethanol-induced gastric ulcer through suppressing NLPR3 inflammasome activation and ferroptosis.

Gastric ulcer (GU) is a prevalent and life-threating gastrointestinal disorder. Aldehyde dehydrogenase 2 (ALDH2) is a pivotal component of alcohol metabolism which has been supported to suppress oxidative stress-elicited DNA damage in gastric mucosa cells. Nonetheless, whether ALDH2 is also involved in GU remains indistinct. Firstly, HCl/ethanol-induced experimental rat GU model was successfully established. RT-qPCR and Western blot tested ALDH2 expression in rat tissues. Following the addition of ALDH2 activator Alda-1, gastric lesion area and index were measured. H&E staining detected the histopathology of gastric tissues. ELISA examined the levels of inflammatory mediators. Alcian blue staining evaluated mucus production of gastric mucosa. Oxidative stress levels were estimated by corresponding kits and Western blot. Western blot examined the expression of NLRP3 inflammasome- and ferroptosis-related proteins. Prussian blue staining and corresponding assay kits measured ferroptosis. In ethanol-treated GES-1 cells, NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome, iron content, ferroptosis, inflammation and oxidative stress were detected as aforementioned above. In addition to that, DCFH-DA staining examined ROS generation. The experimental data corroborated that ALDH2 expression was declined in the tissues of HCl/ethanol-treated rats. Alda-1 ameliorated HCl/ethanol-stimulated gastric mucosal damage, inflammatory response, oxidative stress, NLRP3 inflammasome activation and ferroptosis in rats. Also, the suppressive role of ALDH2 in inflammatory response and oxidative stress was reversed by ferroptosis activator erastin or NLRP3 activator nigericin in HCl/ethanol-challenged GES-1 cells. To be summarized, ALDH2 might play the protective role in the process of GU.

A novel UPLC-ESI-MS assay for fifteen portal estrogens and metabolites detection and application in hepatic fibrosis.

Estrogens and their metabolites (EMs) are involved in chronic liver disease and gut microbiota regulates estrogen metabolism, whereas the role of enterogenous EMs in liver disease is still elusive. Because of the extremely low level of EMs in portal serum and the EMs contain multiple pairs of isomers, an accurate determination of portal serum EMs is urgently needed. This study established a quantitative detection method for portal serum EMs and applied to non-alcoholic fatty liver disease (NAFLD) related hepatic fibrosis mice model. The serum was derived with a novel derivatization reagent 4-acetyl aminobenzene sulfonyl chloride, and a UPLC-ESI-MS system was used for quantification of 15 EMs in 120 min. Compared with normal group, the concentrations of E1, E2 in model group were significantly decreased by 4-8 times, all the C2 and C4 substitution products (2-OHE1, 2-OHE2, 2-MeOE1, 4-OHE1, 4-MeOE1, 4-OHE2, 4-MeOE2, 2-MeOE2) were significantly decreased by 2-22 times. However, the C16 and C17 substitution products (E3, 16-epiE3, 17-epiE3, 16-ketoE2) levels were increased by 3-5 times (P < 0.01). This study elucidated the changes of enterogenous EMs which entered the liver via portal vein in NAFLD - related hepatic fibrosis and provided methodological platform for other related studies on estrogen metabolism.

IL1RAP Knockdown in LPS-Stimulated Normal Human Astrocytes Suppresses LPS-Induced Reactive Astrogliosis and Promotes Neuronal Cell Proliferation.

The reactivation of astrocytes plays a critical role in spinal cord injury (SCI) repairment. In this study, IL1RAP expression has been found to be upregulated in SCI mice spinal cord, SCI astrocytes, and LPS-stimulated NHAs. Genes correlated with IL1RAP were significantly enriched in cell proliferation relative pathways. In LPS-stimulated NHAs, IL1RAP overexpression promoted NHA cell proliferation, decreased PTEN protein levels, and increased the phosphorylation of Akt and mTOR. IL1RAP overexpression promoted LPS-induced NHA activation and NF-κB signaling activation. Conditioned medium from IL1RAP-overexpressing NHAs inhibited SH-SY5Y cells viability but promoted cell apoptosis. Conclusively, IL1RAP knockdown in LPS-stimulated NHAs could partially suppress LPS-induced reactive astrogliosis, therefore promoting neuronal cell proliferation.

Polysaccharide-Based Injectable Hydrogels with Fast Gelation and Self-Strengthening Mechanical Kinetics for Oral Tissue Regeneration.

Oral defects lead to a series of function disorders, severely threatening the patients' health. Although injectable hydrogels are widely studied in tissue regeneration, their mechanical performance is usually stationary after implant, without further self-adaption toward the microenvironment. Herein, an injectable hydrogel with programmed mechanical kinetics of instant gelation and gradual self-strengthening along with outstanding biodegradation ability is developed. The fast gelation is realized through rapid Schiff base reaction between biodegradable chitosan and aldehyde-modified sodium hyaluronate, while self-strengthening is achieved via slow reaction between redundant amino groups on chitosan and epoxy-modified hydroxyapatite. The resultant hydrogel also possesses multiple functions including (1) bio-adhesion, (2) self-healing, (3) bactericidal, (4) hemostasis, and (5) X-ray in situ imaging, which can be effectively used for oral jaw repair. We believe that the strategy illustrated here will provide new insights into dynamic mechanical regulation of injectable hydrogels and promote their application in tissue regeneration.

Origin of the enantioselectivity of alcohol dehydrogenase.

Alcohol dehydrogenases (ADH) are a family of enzymes that catalyse the interconversion between ketones/aldehydes and alcohols in the presence of NADPH cofactor. It is challenging to desymmetrise the substituted cyclopentane-1,3-dione by engineering an ADH, while the reaction mechanism of the metal independent ADH remains elusive. Here we measured the conversion of a model substrate 2-benzyl-2-methylcyclopentane-1,3-dione by LbADH and found it predominately gave the (2R,3R) product. Binding mode analysis of the substrate in LbADH from molecular dynamics simulations disclosed the origin of the enantioselectivity of the enzyme; the opening and closing of the loop 191-205 above the substrate are responsible for shaping the binding pocket to orientate the substrate, so as to give different stereoisomer products. Using QM/MM calculations, we elucidated the reaction mechanism of LbADH. Furthermore, we demonstrated the reaction profile corresponding to the production of different stereoisomers, which is in accordance with our experimental observations. This research here will shed a light on the rational engineering of ADH to achieve stereodivergent stereoisomer products.

Investigation of manganese-iron oxide nanocomposite immobilized on powdered activated carbon as an efficient activator of peroxymonosulfate for antibiotics degradation: Conjunction of adsorption, radical and nonradical processes.

Peroxymonosulfate (PMS)-based advanced oxidation processes (AOPs) have gained considerable attention for their efficient oxidation of persistent pollutants. A two-step chemical co-precipitation method was used to prepare a bimetallic nanocomposite (MnOx@Fe3O4) consisting of manganese oxides and ferroferric oxides, supported by powdered activated carbon (PAC). The synthesis of MnOx@Fe3O4-PAC (MFP) was aimed to enhance the degradation efficiency of oxytetracycline (OTC) via the simultaneous adsorption and oxidation processes on the solid-liquid interface. The OTC degradation process in the MFP/PMS system could be well described by pseudo-first-order kinetics. A wide pH range (3-6) was acceptable for MFP to degrade OTC via PMS activation with the highest removal efficiency reaching up to 85.6% (OTC0 = 150 mg/L), while a 60.8% removal efficiency of total organic carbon (TOC) was also attained simultaneously. SO4•- and 1O2, which were bound to the surface, played a crucial role as reactive oxygen species in the degradation of OTC. The combination of PAC, Fe3O4, and MnOx of MFP could enhance the degradation efficiency of OTC and fetch up their defects of separate application. The deduced OTC degradation pathway relied on the findings from UPLC-MS analysis and density functional theory (DFT) calculations. Noteworthy, MFP maintained efficient catalysis performance in the five cycles of stability experiment with neglectable loss of manganese and iron. These results provide valuable understanding of the conjunction of adsorption, radical, and nonradical processes driven by MFP for OTC degradation.

Silk fibroin fibers-based shape memory membrane with Janus wettability for multitiered wearable protection.

Realizing breathable shape memory fiber-based material with antibacterial and waterproof performances is important for multitiered wearable protection to address the increasing concerns of air pollution. Herein, using an alternating electrospinning-electrospraying technology, we develop a fiber-based membrane with Janus wettability based on a silk fibroin nanofibers-substrate (SFNFs), a polyurethane nanospheres-top layer (PUNSs), and a middle layer of PU nanofibers-mat with in-situ grown silver nanoparticles (PUNFs-AgNPs), which serves separately for skin contact, a self-cleaning physical barrier to resist external aerosol/bacteria (PM2.5 filtration efficiency ~ 98.1%), and a bio-barrier that can sterilize harmful particles and inhibit bacteria proliferation (> 95%). This breathable Janus film (SFNFs/PUNFs-AgNPs/PUNSs, SPAP) with an antibacterial filter shows shape memory stretchability enabled by the thermoplastic PU component, which is mechanically adaptive to human body for wearable protection. This work presents a breathable wearable material for air-filtration and anti-bacteria, promising for applications such as wound dressings, medical masks, protection suits, and multifunctional filters. Graphical abstract: An alternating electrospinning-electrospraying technology was proposed to achieve a silk fibroin-based antibacterial membrane with Janus wettability, as well as good skin affinity and breathability, which serves well as physical and bio-barriers for water resistance, PM2.5 filtration (~98.1%) and bacteria inhibition (efficiency of 95%). This shape memory Janus membrane can adapt mechanically to human body curvatures for functional wearable protections. Supplementary Information: The online version contains supplementary material available at 10.1557/s43578-022-00805-w.

Discourse-based psychological intervention alleviates perioperative anxiety in patients with adolescent idiopathic scoliosis in China: a retrospective propensity score matching analysis.

PURPOSE: To evaluate the effectiveness of a discourse-based psychological intervention on perioperative anxiety, pain and life satisfaction of patients with AIS. METHODS: Between April 2018 and February 2021, 116 consecutive patients with AIS undergoing corrective surgery were enrolled in this study, including 51 with personalized psychological intervention (intervention group, IG) and 65 without (control group, CG). After propensity score matching (PSM), patient characteristics, perioperative scores of anxiety and life satisfaction, measured by values of Generalized Anxiety Disorder 7-item Scale (GAD-7) and Life Satisfaction Index Z scale (LSIZ), were recorded. Mixed linear models were used to estimate the influence of intervention group and time of measurement, as well as their interactions, in anxiety and life satisfaction. Data on post-surgical pain in both groups was also collected and analyzed. RESULTS: After PSM, a total of 90 patients (IG, n = 45; CG, n = 45) were enrolled in this study, and the 2 groups were comparable in patients' demographic and baseline characteristics. There were no pre-intervention between-group differences in the degree of anxiety (IG: 3.98 ± 3.27 vs. CG: 3.93 ± 3.20, p = .948, Cohen's d = 0.015), and life satisfaction (IG: 6.56 ± 1.70 vs. CG: 6.67 ± 2.09, p = .783, Cohen's d = -0.058). After surgery, participants in both IG and CG showed improved the levels of anxiety (GAD-7: IG 2.18 ± 1.21; CG 2.87 ± 2.00) and life satisfaction (LSIZ: IG 9.84 ± 2.09; CG 9.02 ± 2.15). A stratified analysis of patients with generalized anxiety disorder showed improved anxiety (GAD-7: IG 3.50 ± 1.22 vs. CG 6.80 ± 2.05, p = .017, Cohen's d = -1.956) and lower pain level (VAS: IG 4.50 ± 1.76 vs. CG 7.00 ± 1.00, p = .017, Cohen's d = -1.747) in the IG than the CG after surgery. CONCLUSIONS: Discourse-based psychological intervention before surgery can improve perioperative anxiety and life satisfaction, and postoperative painful condition, especially for patients with high-leveled pre-surgical anxiety.

Fault Diagnosis of Rolling Bearing Based on a Priority Elimination Method.

Aiming at the fault diagnosis accuracy of rolling bearings is not high enough, and unknown faults cannot be correctly identified. A priority elimination (PE) method is proposed in this paper. First, the priority diagnosis sequence of faults was determined by comparing the ratios of the inter-class distance to the intra-class distance for all faults. Then, the model training and fault diagnosis were carried out in order of the priority sequence, and the samples of the fault that had been identified were eliminated from the data set until all faults were diagnosed. For the diagnosis model, the stacked sparse auto-encoder network (SSAE) was selected to extract the features of the vibration signal. The extreme gradient boosting algorithm (XGBoost) was chosen to identify the fault type. Finally, the method was tested and verified by experimental data and compared with classical algorithms. Research results indicate the following: (1) with the addition of PE based on SSAE-XGBoost, the fault diagnosis accuracy can be improved from 96.3% to 99.27%, which is higher than other methods; (2) for the test set with the samples of unknown faults, the diagnosis accuracy of SSAE-XGBoost with PE can reach 92.34%, which is nearly 6% higher than that without PE and is also obviously higher than other classical fault diagnosis methods with or without PE. The PE method can not only improve the diagnosis accuracy of faults but also identify unknown faults, which provides a new method and way for fault diagnosis.

A Facile and General Oxidative Hydroxylation of Organoboron Compounds: Citric Acid as an Efficient Catalyst in Water to Access Phenolic and Alcoholic Motifs.

An efficient and convenient method for the synthesis of phenols and aliphatic alcohols is described in this paper. The oxidative hydroxylation reaction of various organoboron compounds proceeded smoothly by employing H2O2 as the oxidant and citric acid as the catalyst in water at room temperature to produce phenols and aliphatic alcohols in satisfactory to excellent yields (up to 99% yield). Various synthetically useful functional groups, such as halogen atom, cyano, and nitro groups, remain intact during the oxidative hydroxylation. The developed catalytic system also could accommodate phenylboronic pinacol ester and potassium phenyltrifluoroborate to give the target product good yields.

Regulated Ion/Electron-Conducting Interphase Enables Stable Zinc-Metal Anodes for Aqueous Zinc-Ions Batteries.

Metallic Zinc (Zn) is considered as a remarkably promising anode for aqueous Zn-ion batteries due to its high volumetric capacity and low redox potential. Unfortunately, dendritic growth and severe side reactions destabilizes the electrode/electrolyte interface, and ultimately reduce the electrochemical performance. Here, an artificial protective layer (APL) with a regulated ion and electron-conducting interphase is constructed on the Zn-metal anode to provide excellent interfacial stability in high-rate cycling. The superior ionic and moderate electronic conductivity of the APL derives from the co-embedding of MXene and Zn(CF3 SO3 )2 salts into the polyvinyl alcohol hydrogel, which enables a synergistic effect of local current density reduction during plating and ion transport acceleration during stripping for Zn anode. Furthermore, the high Young's modulus of the protective layer and dendrite-free deposition morphology during cycling suppresses hydrogen evolution reactions (2.5 mmol h-1 cm-2 ) and passivation. As a result, in symmetrical cell tests, the modified battery presents a stable life of over 2000 cycles at ultra-high current density of 20 mA cm-2 . This research presents a new insight into the formation and regulation of stable electrode-electrolyte interface for the Zn-metal anode.

Insight on Cathodes Chemistry for Aqueous Zinc-Ion Batteries: From Reaction Mechanisms, Structural Engineering, and Modification Strategies.

By virtue of low cost, eco-friendliness, competitive gravimetric energy density, and intrinsic safety, more and more attention has increasingly focused on aqueous zinc ion batteries (AZIBs) as a promising alternative for scalable energy storage. However, plagued by a complex interfacial process, sluggish dynamics, lability of electrodes and electrolytes, insufficient energy density, and poor cycle life heavily restrict practical applications of AZIBs, indicating that profound understandings on cathode storage chemistry are necessarily needed. Hence, this paper comprehensively summarizes recent advance in cathodes with critical insight on the energy storage mechanism. Furthermore, the issues and challenges for high-performance cathodes are meticulously explored, presenting inspiring structural engineering and modification strategies. Finally, rational evaluations on representative cathodes are rendered, suggesting the potential development direction of AZIBs.

Timing of early gonadal differentiation and effects of estradiol-17ß treatments on the sex differentiation in Largemouth bass (Micropterus salmoides).

In this study, an efficient estradiol-17ß (E2)-induced feminization method was established based on the timing of early gonadal differentiation in Largemouth bass (Micropterus salmoides). Histological section results showed that from 20 days post-hatch (dph) to 30 dph, the germ cells gradually differentiated into oogonium and spermatic deferent, respectively. Moreover, female-biased genes Foxl2 and Cyp19a1a were up-regulated to the first peak at 20 dph, while the male-biased genes Dmrt1 were up-regulated to the first peak at 30 dph. These results indicated that the timing of early gonadal differentiation in Largemouth bass was between 20 and 30 dph. Therefore, 15 dph Largemouth bass with a body length of 15.10 ± 0.09 mm were chosen, and four E2-treated diets were set as 0 (E0, control), 50 mg/kg E2 (E50), 100 mg/kg E2 (E100), and 200 mg/kg E2 (E200). After feeding with E2-treated diets for 60 days, female ratios were 55%, 100%, 100%, and 100% in E0, E50, E100, and E200 groups, respectively. No intersex fish were observed in all the groups. However, 30% of females in the E200 group possessed thinner ovaries, with smaller ovary cavity structures and a decreased number of primary oocyte cells than those in other groups. Besides, the Largemouth bass in the E0 group grew more than those in E50, E100, and E200 groups during the E2 treatments period (P < 0.05). In conclusion, our study suggested that 50-100 mg/kg E2-treated diets could effectively induce the feminization of 15 dph Largemouth bass within 60 days duration time, which provided valuable information for the breeding of the all-male Largemouth bass population.