Addition Strategies Research Articles

Optimal strategy for stabilizing protein folding intermediates.

To manipulate the protein concentration at a certain functional state through chemical stabilizers is crucial for protein-related studies. It not only plays a key role in protein structure analysis and protein folding kinetics, but also affects protein functionality to a large extent and thus has wide applications in medicine, food industry, etc. However, due to concerns about side effects or financial costs of stabilizers, identifying optimal strategies for enhancing protein stability with a minimal amount of stabilizers is of great importance. Here, we prove that either for the fixed terminal time (including both finite and infinite cases) or for the free one, the optimal control strategy for stabilizing the folding intermediates with a linear strategy for stabilizer addition belongs to the class of bang-bang controls. The corresponding optimal switching time is derived analytically, whose phase diagram with respect to several key parameters is explored in detail. The bang-bang control will be broken when nonlinear strategies for stabilizer addition are adopted. Moreover, the above theory is applied to the stabilization of erythropoietin by ten different kinds of chemicals, providing theoretical guidance for the selection and rational usage of stabilizers. Our current study on optimal strategies for protein stabilizers not only offers deep insights into the general picture of protein folding kinetics but also provides valuable theoretical guidance on treatments for protein-related diseases in medicine.

Effects of ZnO additive on the electrical and densification properties of A-site deficient barium cerate perovskite

The dual strategies of A-site deficiency and addition of ZnO sintering aid have been employed to optimise stability and densify the high-temperature proton conductor Ba0.95Ce0.8Y0.2O3-δ at 1200 °C (B95CYZn-1200). Structural analysis performed by Rietveld refinement based on X-ray diffraction data indicated perovskite phase with monoclinic symmetry (space group, I2/m). Raman spectroscopy revealed the presence of ZnO for material sintered at 1200 °C, which most likely partially resides in grain-boundary regions, leading to enhanced electrical transport observed by impedance spectroscopy at low temperature. Anomalous and reproducible frequency-dependent impedance behaviour below 500 °C, observed in various atmospheres, is suggested to be attributable to the varistor-type properties of ZnO. The electrical conductivity of B95CYZn-1200 in the range 500–900 °C is typical of perovskite proton conductors but with greater conductivity than both Ba-stoichiometric BaCe0.8Y0.2O3-δ and ZnO-free Ba0.95Ce0.8Y0.2O3-δ in wet O2 and N2, reaching ∼ 1.1 S m−1 at 550 °C in wet O2. Resistance to carbonate formation and mechanical breakdown was demonstrated via prolonged impedance measurements in CO2- and H2-containing atmospheres in the range 600–700 °C.

Intensive coagulation of secondary effluent to mitigate reverse osmosis membrane fouling at low temperatures: Strategies of pre-oxidation and coagulant aids addition

Conventional coagulation-sedimentation, typically used as a pretreatment for ultrafiltration-reverse osmosis, is ineffective in solving the problem of reverse osmosis membrane fouling at low temperatures. In this study, the coagulation enhancement effect of pre-oxidation and the addition of coagulant aids on conventional coagulation with polyaluminum chloride as a coagulant was investigated. The results showed that the addition of fly ash, powdered activated carbon, or diatomite as coagulant aids improved the reduction of turbidity, dissolved organic carbon (DOC), and ultraviolet absorbance at 254 nm (UV254), and also reduced the residual content of dissolved aluminum ions. Among them, diatomite was superior. Pre-oxidation before conventional coagulation increased the reduction of turbidity and UV254 by about 50 % and doubled the removal of proteins, polysaccharides, and DOC compared to conventional coagulation. Ozone was superior to sodium hypochlorite. The combination of ozone pre-oxidation and diatomite addition with conventional coagulation further increased the pollutant removal rate, with the removal rates of turbidity, UV254, polysaccharides, proteins, and DOC reaching 82.20 %, 52.35 %, 26.34 %, 24.89 %, and 26.38 %, respectively. In addition, the residual content of dissolved aluminum ions decreased to 0.84 mg/L. The reverse osmosis filtration simulation test showed that pretreating the feed water with the enhanced coagulation by the combination of ozone pre-oxidation and diatomite addition resulted in a slower decrease in membrane flux, reduced foulant content on the membrane surface, and the smallest increase in contact angle. The results of this research may offer a viable pretreatment method to reduce fouling in reverse osmosis membranes operating at low temperatures.

An efficient strategy for alkoxy halogenation addition of olefins catalyzed by polyoxometalate-based iron catalyst

An efficient strategy for alkoxy halogenation addition of olefins catalyzed by polyoxometalate-based iron catalyst

Diaminodiphenylmethane modified zirconium phosphate: A new strategy for trace addition to improve flame retardancy, smoke inhibition, and compatibility of epoxy resins

AbstractHigh‐efficient flame retardants (ZrP‐DDM) were synthesized successfully via ion‐exchange method, using diaminodiphenylmethane (DDM) modified layered zirconium phosphate (α‐ZrP). Trace addition of ZrP‐DDM in epoxy resins (EP) can enhance the flame‐retardant, smoke‐inhibition, mechanical, and thermal stability properties of EP composites. As shown in the results, ZrP‐DDM exhibits a better synergistic effect than α‐ZrP, and the EP composites containing 0.5 wt% ZrP‐DDM (EP/0.5ZrP‐DDM) show excellent flame‐retardant and smoke‐inhibition properties. Especially, EP/0.5ZrP‐DDM possesses a limiting oxygen index (LOI) of 33.7% with UL94 V‐1 rating, while the EP composites containing 0.5 wt% ZrP (EP/0.5ZrP) has a LOI of 30.1% and fails to achieve the UL94 rating. Furthermore, the peak heat release rate (PHRR), total heat release rate (THR), and smoke density rating of EP/0.5ZrP‐DDM decrease by 10.2%, 3.7%, and 8.2% compared with EP/0.5ZrP. Based on condensed‐phase product analysis, EP/ZrP‐DDM sample provides a gas source for intumescent char layer, and produces a stable phosphorus‐rich crosslinking structures during combustion, thus decreasing the fire hazard of the composite material. Meanwhile, the introduction of ZrP‐DDM has a less impact on tensile strength of EP composites compared with α‐ZrP, suggesting the addition of ZrP‐DDM effectively enhances the compatibility with the EP matrix, thereby maintaining excellent mechanical properties of the EP matrix.

The prevalence of and factors associated with depressive and anxiety symptoms during the COVID-19 pandemic among healthcare workers in South Africa.

Healthcare workers globally have experienced increased social and occupational stressors in their working environments and communities because of COVID-19 which has increased the risk of mental health concerns. This study aimed to explore the prevalence and correlates of depression and anxiety amongst healthcare workers during the COVID-19 pandemic in the Western Cape, South Africa. In addition, role-related stressors and coping strategies were explored. We conducted a cross-sectional survey of doctors and nurses working in public healthcare facilities across the Western Cape, South Africa. Participants completed the Generalized Anxiety Disorder-7 (GAD-7), the Center for Epidemiologic Studies Depression (CES-D), the Professional Quality of Life (PROQL-R-IV), and the Brief Coping Orientation to Problems Experienced (COPE-R) scales. Data were analysed using multivariable logistic regression analysis. The sample comprised 416 health workers (303 nurses, 113 doctors). Almost 40% of the sample (n = 161) had CES-D scores suggestive of probable depression, and 45.9% (n = 186) had GAD-7 scores suggestive of anxiety. In the logistic regression model, the odds of probable depression were higher for female participants compared to men (OR = 2.26, 95% CI 1.00-5.10) and for participants who used behavioural disengagement as a coping strategy (OR = 1.50, 95% CI 1.14-1.97). More time spent working with COVID patients was associated with increased odds of having high levels of anxiety [OR = 1.13, 95% CI (1.02-1.25). Substance use (OR = 1.39, 95% CI 1.08-1.81), venting (OR = 1.31, 95% CI 1.01-1.70), and self-blame (OR = 1.42, 95% CI 1.08-1.87) were some of the coping strategies used by healthcare workers. High levels of secondary traumatic stress and burnout were found to increase the odds of both depression and anxiety. Findings of this study suggest that there is a high prevalence of mental health issues among healthcare workers, and a critical need to focus on workplace mental health interventions to support these frontline workers.

Exploring the Stabilization of Phenolic Material and Red Wine Color through Different Polysaccharide Extraction and Addition Strategies

Exploring the Stabilization of Phenolic Material and Red Wine Color through Different Polysaccharide Extraction and Addition Strategies

Empowering Protein Engineering through Recombination of Beneficial Substitutions.

Directed evolution stands as a seminal technology for generating novel protein functionalities, a cornerstone in biocatalysis, metabolic engineering, and synthetic biology. Today, with the development of various mutagenesis methods and advanced analytical machines, the challenge of diversity generation and high-throughput screening platforms is largely solved, and one of the remaining challenges is: how to empower the potential of single beneficial substitutions with recombination to achieve the epistatic effect. This review overviews experimental and computer-assisted recombination methods in protein engineering campaigns. In addition, integrated and machine learning-guided strategies were highlighted to discuss how these recombination approaches contribute to generating the screening library with better diversity, coverage, and size. A decision tree was finally summarized to guide the further selection of proper recombination strategies in practice, which was beneficial for accelerating protein engineering.

Iron deficiency suppresses the Fenton reaction and boosts photosynthetic H2 production in bisulfite-treated Chlamydomonas cells

Adding bisulfite is a significant strategy to enhance H2 photoproduction, but it adversely affects photosystem II (PSII) activity in microalgae, consequently limiting H2 production. Nevertheless, the exact mechanism through which bisulfite disrupts PSII remains unclear. Here, the addition of NaHSO3 to Chlamydomonas reinhardtii cultures suppresses growth by inducing iron poisoning through the Fenton reaction, driven by reduced iron demand and the resultant accumulation of iron. Consequently, the removal of iron from C. reinhardtii cultures eliminates the iron poisoning triggered by the Fenton reaction. This, in turn, mitigates PSII impairment and leads to a significant increase in photosynthetic H2 production in C. reinhardtii cells. Collectively, these discoveries unveil the precise mechanism by which bisulfite disrupts PSII, opening up a new avenue for substantially enhancing green hydrogen production from microalgae through the bisulfite addition strategy.

Application of biofloc technology in the larval rearing of zebrafish (Danio rerio)

The aim of this study was to investigate the different strategies of biofloc addition to zebrafish (Danio rerio) larviculture, and evaluate their growth and biochemical parameters. Three treatments were used: addition of 200 mL biofloc once at the start of the assay (O1), addition of 100 mL biofloc every seven days (1W), and addition of 100 mL biofloc every four days (2W). The 1W and 2W treatments also received 200 mL biofloc at the start of the assay. Regarding water quality, the only difference was the total suspended solid concentration, because the 2W treatment had a higher concentration in the final assay (127.6 ± 24.3 mg L-1). The final weight, survival rate, and juvenile percentile did not show statistical differences among the treatments. However, the O1 treatment exhibited a higher total length (11.93 ± 0.45 mm) than those in the 2W treatment. The juveniles in the 2W treatment exhibited lower nonprotein thiols and higher TBARS concentrations than those in the other treatments. Thus, the biofloc system can be a viable alternative to zebrafish larviculture without the use of conventional live food, and the addition of biofloc once (O1) at the beginning of larval rearing achieves good growth and survival results.

Estimating the global prevalence of chronic obstructive pulmonary disease (COPD): a systematic review and meta-analysis

BackgroundChronic obstructive pulmonary disease (COPD) is a major public health problem. The present study aims to provide a global and regional estimate of the prevalence of COPD based on spirometry according to the two most widely used diagnostic criteria of COPD: fixed ratio (FR) and lower limit of normal (LLN).MethodsWe conducted a systematic review of the literature according to PRISMA guidelines. MEDLINE, Web of Sciences, and Scopus databases were searched to identify studies on the spirometry-based prevalence of COPD in individuals aged 40 years and older. The meta-analysis was performed using MedCalc 19 software.ResultsIn total, 42 of the 3393 studies reviewed were eligible for inclusion. The overall prevalence of COPD in people aged 40 years and older was 12.64% (95% CI 10.75%-14.65%) and 7.38% (95% CI 5.47% − 9.55%) based on FR and LLN criteria, respectively. By gender, men had a higher prevalence of COPD compared to women (15.47%; 95% CI 12.22%-19.02% for men versus 8.79%; 95% CI 6.94%-10.82% for women). Using the LLN criteria, the prevalence of COPD in both sexes was almost identical (8.67%; 95% CI 8.44%- 8.90% for men and 8.00%; 95% CI 6.42% − 9.73% for women). We reported a high prevalence of COPD among smokers and the elderly by both definitions of airway obstruction. Regional prevalence estimates using the FR definition indicate that the highest COPD prevalence was recorded in the Americas and the lowest was recorded in the Eastern Mediterranean region. Using the LLN definition, the highest prevalence was recorded in the Southeast Asian region and the lowest prevalence was recorded in the American region. The most common COPD stage was stage II, with a prevalence of 50.46%. The results indicate a huge lack of prevalence data in the African and Eastern Mediterranean region. The results were given using a random-effect model due to the high heterogeneity between studies.ConclusionResults show that the prevalence of COPD differs according to the diagnostic criteria used. In addition, management and prevention strategies targeting risk factors for COPD are certainly needed to reduce the global burden of this chronic respiratory disease.

Primary students’ relational thinking and computation strategies with concrete-to-symbolic representations of subtraction as difference

Children are highly inclined to attend to the properties of numbers, operations and equality when given helpful tools for doing so. Our aim was to investigate early algebraic thinking with the compensation property of equality for subtraction. We provided 22 (9–11-year-old) students with physical blocks for building vertical towers and conducted individual interviews with them as they completed a sequence of 15 tasks involving subtraction as difference using concrete, numeric, and symbolic representations. Relational thinking was evidenced across a range of subtraction calculation skill levels. Those students who could use both indirect addition and take-away strategies flexibly, depending on the size of the numbers involved, were more likely to evidence attention to generality with symbolic equations. The shift to symbolic equations elicited some students’ productive attempts to connect subtraction as difference and subtraction as take way but seemed to hinder others by provoking a return to take away calculations rather than relational thinking strategies.

Self-reporting and Biodegradable Thermosetting Solid Polymer Electrolyte.

To date, significant efforts have been dedicated to improve their ionic conductivity, thermal stability, and mechanical strength of solid polymer electrolytes (SPEs). However, direct monitoring of physical and chemical changes in SPEs is still lacking. Moreover, existing thermosetting SPEs are hardly degradable. Herein, by overcoming the limitation predicted by Flory theory, self-reporting and biodegradable thermosetting hyperbranched poly(β-amino ester)-based SPEs (HPAE-SPEs) are reported. HPAE is successfully synthesized through a well-controlled "A2+B4" Michael addition strategy and then crosslinked it in situ to produce HPAE-SPEs. The multiple tertiary aliphatic amines at the branching sites confer multicolour luminescence to HPAE-SPEs, enabling direct observation of its physical and chemical damage. After use, HPAE-SPEs can be rapidly hydrolysed into non-hazardous β-amino acids and polyols via self-catalysis. Optimized HPAE-SPE exhibits an ionic conductivity of 1.3×10-4 S/cm at 60 °C, a Na+ transference number ( ) of 0.67, a highly stable sodium plating-stripping behaviour and a low overpotential of ≈190 mV. This study establishes a new paradigm for developing SPEs by engineering multifunctional polymers. The self-reporting and biodegradable properties would greatly expand the scope of applications for SPEs.

Self‐reporting and Biodegradable Thermosetting Solid Polymer Electrolyte

AbstractTo date, significant efforts have been dedicated to improve their ionic conductivity, thermal stability, and mechanical strength of solid polymer electrolytes (SPEs). However, direct monitoring of physical and chemical changes in SPEs is still lacking. Moreover, existing thermosetting SPEs are hardly degradable. Herein, by overcoming the limitation predicted by Flory theory, self‐reporting and biodegradable thermosetting hyperbranched poly(β‐amino ester)‐based SPEs (HPAE‐SPEs) are reported. HPAE is successfully synthesized through a well‐controlled “A2+B4” Michael addition strategy and then crosslinked it in situ to produce HPAE‐SPEs. The multiple tertiary aliphatic amines at the branching sites confer multicolour luminescence to HPAE‐SPEs, enabling direct observation of its physical and chemical damage. After use, HPAE‐SPEs can be rapidly hydrolysed into non‐hazardous β‐amino acids and polyols via self‐catalysis. Optimized HPAE‐SPE exhibits an ionic conductivity of 1.3×10−4 S/cm at 60 °C, a Na+ transference number ( ) of 0.67, a highly stable sodium plating‐stripping behaviour and a low overpotential of ≈190 mV. This study establishes a new paradigm for developing SPEs by engineering multifunctional polymers. The self‐reporting and biodegradable properties would greatly expand the scope of applications for SPEs.

Transition metal modified Al2O3 mesoporous nanospheres for catalysis of organic reactions

The performance of metal oxide-based catalysts are usually determined by their characteristics such as material composition, morphology, and surface/interface properties. Therefore, rational design of metal oxide-based catalysts with special surface/interface characteristics and porous microstructure still needs further research. In this work, a facile two-step solvothermal-annealing method is developed for the synthesis of transition metal (TM) modified Al2O3 (TM-Al2O3, TM = Cu, Fe, Ni, Co) nanospheres. The influences of different ratios of solvents (e.g., water and glycerol) on the morphology and particle size of the nanocatalysts are explored. Benefitting from the nano-spherical morphology and unique mesoporous structure, the representative catalyst (i.e., Cu-Al2O3) exhibits favorable catalytic performance in 4-nitrophenol reduction and benzyl alcohol oxidization reactions. The turnover frequency of Cu-Al2O3 is high up to 35.9 min−1 for the reduction of 4-nitrophenol, which is higher than that of its counterparts (i.e., Fe-Al2O3, Ni-Al2O3, and Ni-Al2O3) and many recently reported Al2O3-based catalysts. Moreover, the pH of the reaction system is regulated to enhance the catalytic efficiency in selective oxidization of benzyl alcohol by an additive addition strategy. These results suggest that the nano-spherical and mesoporous morphology is indeed effective for the activity enhancement of TM-Al2O3 catalysts. The same catalyst designing concept and performance regulation strategy may be extended to other TM-modified metal oxide systems, making it possible to tune the catalytic behavior for various chemical reactions.

Anus preservation in low rectal adenocarcinoma based on MMR/MSI status (APRAM): a study protocol for a randomised, controlled, open-label, multicentre phase III trial

BackgroundAnus preservation has been a challenge in the treatment of patients with low rectal adenocarcinoma (within 5 cm from the anal verge) because it is difficult to spare the anus with its functioning sphincter complex under the safe margin of tumour resection. Patients with dMMR/MSI-H can achieve a favourable complete response (CR) rate by using a single immune checkpoint inhibitor. For patients with pMMR/MSS/MSI-L, intensified neoadjuvant three-drug chemotherapy may be the preferred option for anal preservation. In addition, the watch and wait (W&W) strategy has been proven safe and feasible for patients with rectal cancer who achieve a clinical complete response (cCR). Therefore, we initiated this clinical trial to explore the optimal neoadjuvant treatment pattern for patients with low locally advanced rectal cancer (LARC) with different MMR/MSI statuses, aiming to achieve a higher cCR rate with the W&W strategy and ultimately provide more patients with a chance of anus preservation.MethodsThis is a randomised, controlled, open-label, multicentre phase III trial. Patients with clinical stage T2-4 and/or N + tumours located within 5 cm from the anal verge are considered eligible. Based on the results of pathological biopsy, the patients are divided into two groups: dMMR/MSI-H and pMMR/MSS. Patients in the dMMR/MSI-H group will be randomly allocated in a 1:1 ratio to either arm A (monoimmunotherapy) or arm B (short-course radiotherapy followed by monoimmunotherapy). Patients in the pMMR/MSS group will be initially treated with long-term pelvic radiation with concurrent capecitabine combined with irinotecan. Two weeks after the completion of chemoradiotherapy (CRT), the patients will be randomly allocated in a 1:1 ratio to arm C (XELIRI six cycle regime) or arm D (FOLFIRINOX nine cycle regime). The irinotecan dose will be adjusted according to the UGT1A1-genotype. After treatment, a comprehensive assessment will be performed to determine whether a cCR has been achieved. If achieved, the W&W strategy will be adopted; otherwise, total mesorectal excision (TME) will be performed. The primary endpoint is cCR with the maintenance of 12 months at least, determined using digital rectal examination, endoscopy, and rectal MRI or PET/CT as a supplementary method.DiscussionAPRAM will explore the best anus preservation model for low LARC, combining the strategies of consolidation chemotherapy, immunotherapy, and short-course radiotherapy, and aims to preserve the anus of more patients using W&W. Our study provides an accurate individual treatment mode based on the MMR/MSI status for patients with low LARC, and more patients will receive the opportunity for anus preservation under our therapeutic strategy, which would transform into long-term benefits.Trial registrationClinicaltrials.gov NCT05669092 (Registered 28th Nov 2022).

2-Hydroxy-1,4-Naphthoquinone: A Promising Redox Mediator for Minimizing Dissolved Organic Nitrogen and Eutrophication Effects of Wastewater Effluent.

Researchers and engineers are committed to finding effective approaches to reduce dissolved organic nitrogen (DON) to meet more stringent effluent total nitrogen limits and minimize effluent eutrophication potential. Here, we provided a promising approach by adding specific doses of 2-hydroxy-1,4-naphthoquinone (HNQ) to postdenitrification bioreactors. This approach of adding a small dosage of 0.03-0.1 mM HNQ effectively reduced the concentrations of DON in the effluent (ANOVA, p < 0.05) by up to 63% reduction of effluent DON with a dosing of 0.1 mM HNQ when compared to the control bioreactors. Notably, an algal bioassay indicated that DON played a dominant role in stimulating phytoplankton growth, thus effluent eutrophication potential in bioreactors using 0.1 mM HNQ dramatically decreased compared to that in control bioreactors. The microbe-DON correlation analysis showed that HNQ dosing modified the microbial community composition to both weaken the production and promote the uptake of labile DON, thus minimizing the effluent DON concentration. The toxic assessment demonstrated the ecological safety of the effluent from the bioreactors using the strategy of HNQ addition. Overall, HNQ is a promising redox mediator to reduce the effluent DON concentration with the purpose of meeting low effluent total nitrogen levels and remarkably minimizing effluent eutrophication effects.

Redundancy-Free Self-Supervised Relational Learning for Graph Clustering.

Graph clustering, which learns the node representations for effective cluster assignments, is a fundamental yet challenging task in data analysis and has received considerable attention accompanied by graph neural networks (GNNs) in recent years. However, most existing methods overlook the inherent relational information among the nonindependent and nonidentically distributed nodes in a graph. Due to the lack of exploration of relational attributes, the semantic information of the graph-structured data fails to be fully exploited which leads to poor clustering performance. In this article, we propose a novel self-supervised deep graph clustering method named relational redundancy-free graph clustering (R 2 FGC) to tackle the problem. It extracts the attribute-and structure-level relational information from both global and local views based on an autoencoder (AE) and a graph AE (GAE). To obtain effective representations of the semantic information, we preserve the consistent relationship among augmented nodes, whereas the redundant relationship is further reduced for learning discriminative embeddings. In addition, a simple yet valid strategy is used to alleviate the oversmoothing issue. Extensive experiments are performed on widely used benchmark datasets to validate the superiority of our R 2 FGC over state-of-the-art baselines. Our codes are available at https://github.com/yisiyu95/R2FGC.

High-efficiency and conveniently recyclable g-C3N4/diatomite/calcium alginate composite gel bead photocatalysts

Graphitic carbon nitride (g-C3N4) is considered an encouraging photocatalyst with visible light activity. However, the utilization of g-C3N4 nanosheets in powdered form in wastewater treatment presents difficulties in the recovery and recycling of photocatalysts. Consequently, supported g-C3N4 photocatalysts have been developed for practical applications. In the present work, a novel, conveniently recyclable composite gel bead photocatalyst, comprised of g-C3N4/diatomite/calcium alginate, has been fabricated using a dropwise addition strategy. The systematic investigation of photocatalytic activity and photochemical stability of the composite gel beads was conducted through the degradation of methylene blue (MB) under visible light exposure (λ > 420 nm). As a result, g-C3N4/diatomite/calcium alginate gel beads show a high photocatalytic effectiveness of 95% when MB solution is disintegrated at 120 minutes.

Combination of dimensional reduction and active site addition strategies for preparing unique {RE9}-cluster-based MOFs: efficient CO2 fixation and Knoevenagel condensation

A series of 2D {RE9}-cluster-based rare-earth MOFs were built by dimensional reduction and active site addition strategies. They exhibit excellent catalytic activity in CO2 fixation and Knoevenagel condensation under mild conditions.