Boosting organic solar cell efficiency via tailored end-group modifications of novel non-fused ring electron acceptors.

In this study, we designed and synthesized two NFREAs, 2BTh-3F and 2BTh-CN, incorporating distinct substituents to modulate their electron-withdrawing properties. We meticulously explore the distinct impacts of these substituents on NFREA performance. Our investigation revealed that the introduction of 3,5-difluoro-4-cyanophenyl in 2BTh-CN significantly enhanced electron withdrawal and intramolecular charge transfer, leading to a red-shifted absorption spectrum and optimized energy levels. Consequently, organic solar cells (OSCs) utilizing 2BTh-CN demonstrate a notable power conversion efficiency (PCE) of 15.07%, outperforming those employing 2BTh-3F (PCE of 9.34%). Moreover, by incorporating 2BTh-CN into the D18:2BTh-C2 system as a third component, we achieve a PCE exceeding 17% in a high-performing ternary OSC, ranking among the most efficient NFREA-based OSCs reported to date. Overall, our study underscores the potential of deliberate design and optimization of non-fused ring acceptor molecular structures to attain outstanding photovoltaic performance.

Highly efficient and stable binary and ternary organic solar cells using polymerized nonfused ring electron acceptors.

This study reports the successful design and synthesis of two novel polymerized nonfused ring electron acceptors, P-2BTh and P-2BTh-F, derived from the high-performance nonfused ring electron acceptor, 2BTh-2F. Prepared via Stille polymerization, these polymers feature thiophene and fluorinated thiophene as π-bridge units. Notably, P-2BTh-F, with difluorothiophene as the π-bridge, exhibits a more planar backbone and red-shifted absorption spectrum compared with P-2BTh. When employed in organic solar cells (OSCs) with PBDB-T as the donor material, P-2BTh-F-based devices demonstrate an outstanding power conversion efficiency (PCE) of over 11%, exceeding the 8.7% achieved by P-2BTh-based devices. Furthermore, all-polymer solar cells utilizing PBDB-T:P-2BTh-F exhibit superior storage stability. Additionally, P-2BTh-F was explored as a functional additive in a high-performance binary system, enhancing stability while maintaining comparable PCE (19.45%). This strategy offers a cost-effective approach for fabricating highly efficient and stable binary and ternary organic solar cells, opening new horizons for cost-effective and durable solar cell development.

Boosting Organic Solar Cells to Over 18% Efficiency through Dipole-Dipole Interactions in Fluorinated Nonfused Ring Electron Acceptors.

This study successfully designed and synthesized two nonfused ring electron acceptors, 412-6F and 412-6Cl, modified with fluorine and chlorine substituents, respectively. Single-crystal analysis revealed that 412-6F possesses a planar molecular backbone and exhibits pronounced dipole-dipole interactions between the fluorine atoms on the lateral phenyl groups and the carbonyl oxygen atoms on the end groups. This specific interaction promotes dense end-group stacking, leading to a reduced interlayer spacing. Improved crystallinity and coherence length are observed in the D18:412-6F blend film. Conversely, 412-6Cl adopts a more distorted configuration and lacks these interactions. As a result, the organic solar cell (OSC) based on D18:412-6F achieved a remarkable power conversion efficiency of 18.03%, surpassing the performance of the D18:412-6Cl OSC. This underscores the importance of designing novel acceptors with beneficial intermolecular interactions to enhance OSC efficiency, thus providing a new direction for organic photovoltaic advancement.

Clinical study of 57 cases of endovascular treatment for total subclavian artery occlusion.

OBJECTIVE: To investigate the safety and efficacy of endovascular treatment for totally occlusive lesions of the subclavian artery (SCA). METHODS: A retrospective study was performed on 57 patients treated with angioplasty and stenting, including 42 males and 15 females, with an average age of 61.8 years (range: 49 to 81 years). Efficacy, safety, and complications were evaluated. RESULTS: Procedural success was achieved for 47/57 patients and symptoms were relieved. Rat-tail occlusion is the most common type, and all cases were successfully recanalized. Plain type occlusion is less common with a recanalization rate of 55.6%. Hilly and plain occlusions are the main types of stent implantation failure. Through univariate analysis and trend matching analysis, the type of SCA occlusion and surgical approach had statistical significance on the success rate of surgery. The mean follow-up time was 34.6 ± 16.2 months. The cumulative stent patency rates at 1, 3, and 5 years were 95.5%, 86.4%, and 77.3% in the calcified plaque group and 92.0%, 76.0%, and 68.0% in the non-calcified plaque group, respectively. The 3-year and 5-year patency rates in the calcified plaque group were higher than those in the non-calcified plaque group (p < .05). CONCLUSION: Different occlusion types and surgical approaches can affect the surgical success rate. The combined femoral and brachial approach can improve the rate of recanalization of SCA occlusions. The patency rates at 3 and 5 years in the calcified plaque group were higher than those in the non-calcified plaque group.

A 3,3'-Difluoro-2,2'-Bithiophene Based Donor Polymer Realizing High Efficiency (>17%) Single Junction Binary Organic Solar Cells.

In this study, two novel donor-acceptor (D-A) copolymers are designed and synthesized, DTBT-2T and DTBT-2T2F with 2,2'-bithiophene or 3,3'-difluoro-2,2'-bithiophene as the donor unit and dithienobenzothiadiazole as the acceptor unit, and used them as donor materials in non-fullerene organic solar cells (OSCs). Due to enhanced planarity of polymer chains resulted by the intramolecular F···S noncovalent interactions, the incorporation of 3,3'-difluoro-2,2'-bithiophene unit instead of 2,2'-bithiophene into the polymers can enhance their molecular packing, crystallinity and hole mobility. The DTBT-2T:L8-BO based binary OSCs deliver a power conversion efficiency (PCE) of only 9.71% with a Voc of 0.78 V, a Jsc of 20.69 mA cm-2 , and an FF of 59.67%. Moreover, the introduction of fluoro atoms can lower the highest occupied molecular orbital levels. As a result, DTBT-2T2F:L8-BO based single-junction binary OSCs exhibited less recombination loss, more balanced charge mobility, and more favorable morphology, resulting in an impressive PCE of 17.03% with a higher Voc of 0.89 V, a Jsc of 25.40 mA cm-2, and an FF of 75.74%. These results indicate that 3,3'-difluoro-2,2'-bithiophene unit can be used as an effective building block to synthesize high performance polymer donor materials. This work greatly expands the selection range of donor units for constructing high-performance polymers.

Enhancing Protease and Amylase Activities in Bacillus licheniformis XS-4 for Traditional Soy Sauce Fermentation Using ARTP Mutagenesis.

This study was conducted to increase the enzymatic activity of Bacillus licheniformis XS-4, which was isolated from the traditional fermented mash of Xianshi soy sauce. The mutation was induced by atmospheric and room-temperature plasma (ARTP), and a mutant strain, mut80, was obtained. mut80 exhibited significant increases in protease and amylase activity by 90.54% and 143.10%, respectively, and the enhanced enzymatic activities were stably maintained after 20 consecutive incubations. Re-sequencing analysis of mut80 revealed that the mutation sites were located in 1518447(AT-T) and 4253106(G-A) in its genome, which was involved in the metabolic pathways of amino acids. The expression of the protease synthetic gene (aprX) increased 1.54 times, while that of the amylase gene (amyA) increased 11.26 times, as confirmed via RT-qPCR. Using ARTP mutagenesis, the present study proposes a highly efficient microbial resource with enhanced protease and amylase activity provided by B. licheniformis, which can potentially be used to improve the efficiency of traditional soy sauce fermentation.

Multiple strategies for the development of multienzyme complex for one-pot reactions.

The main intention in the modern era is to make life and activities on earth more comfortable by adding necessary products through biological machinery. Millions of tons of biological raw materials and lignocellulosic biomass are wasted by burning each year without providing benefits to living organisms. Instead of being the cause of disturbing the natural environment by increasing global warming and pollutants worldwide, now, it is the need of the hour to develop an advanced strategy to utilize these biological raw materials to produce renewable energy resources to meet the energy crisis. The review presents the idea of multiple enzymes in one step to hydrolyze complex biomaterials into useful products. The paper discusses how multiple enzymes are arranged in a cascade for complete hydrolysis of raw material in one-pot to prevent multistep, time consuming, and expensive methods. Furthermore, there was the immobilization of multiple enzymes in a cascade system with in vitro and in vivo conditions for reusability of enzymes. The role of genetic engineering, metabolic engineering, and random mutation techniques is described for the development of multiple enzyme cascades. Techniques that are involved in the improvement of native strain to recombinant strain for the enhancement of hydrolytic capacity were used. The preparative steps, before enzymatic hydrolysis like acid, and base treatment methods are more effective for improving the hydrolysis of biomass by multiple enzymes in a one-pot system. Finally, the applications of one-pot multienzyme complexes in biofuel production from lignocellulosic biomass, biosensor production, medicine, food industry, and the conversion of biopolymers into useful products are described.

Lignin and spent bleaching clay into mono-aromatic hydrocarbons by a cascade dual catalytic pyrolysis system: Critical role of spent bleaching clay.

In the present study, a cascade dual catalytic system was used for the co-pyrolysis of lignin with spent bleaching clay (SBC) to efficiently produce mono-aromatic hydrocarbon (MAHs). The cascade dual catalytic system is composed of calcined SBC (CSBC) and HZSM-5. In this system, SBC not only acts as a hydrogen donor and catalyst in the co-pyrolysis process, but is also used as a primary catalyst in the cascade dual catalytic system after recycling the pyrolysis residues. The effects of different influencing factors (i.e., temperature, CSBC-to-HZSM-5 ratio, and raw materials-to-catalyst ratio) on the system were explored. It was observed that, when the temperature was 550 °C, the CSBC-to-HZSM-5 ratio was 1:1, and when the raw materials-to-catalyst ratio was 1:2, the highest bio-oil yield was 21.35 wt%. The relative MAHs content in bio-oil was 73.34 %, whereas the relative polycyclic aromatic hydrocarbons (PAHs) content was 23.01 %. Meanwhile, the introduction of CSBC inhibited the generation of graphite-like coke as indicated by HZSM-5. This study realizes the full resource utilization of spent bleaching clay and reveals the environmental hazards caused by spent bleaching clay and lignin waste.

Lacticaseibacillus casei T1 attenuates Helicobacter pylori-induced inflammation and gut microbiota disorders in mice.

Probiotics are defined as live microbial food elements that are beneficial to human health. Lacticaseibacillus casei T1 was considered to have potential as a bioactive ingredient in functional foods, which was isolated from kurut. Previous research by our group proved that L. casei T1 could prevent inflammatory responses caused by Helicobacter pylori. This study aimed to investigate whether treatment with L. casei T1 resulted in a suppressive effect on H. pylori-induced oxidative stress and inflammatory responses. The results showed that treatment with L. casei T1 could relieve H. pylori-induced overexpression of inflammatory cytokines in GES-1 cells. Experiments in animals suggested that taking long-term L. casei T1 could reduce oxidative stress and inflammatory cytokines and improve H. pylori-induced gastric mucosal damage. Furthermore, taking L. casei T1 could increase the relative abundance of beneficial intestinal bacterium (Lachnospiraceae and Odoribacter) of H. pylori-infected mice and help in maintaining the balance of intestinal microflora.Collectively, L. casei T1 had certain degrees of therapeutic effect against H. pylori. In the future, it combined with antibiotics for H. pylori eradication deserves further study.

Effect of Steric Hindrance at the Anthracene Core on the Photovoltaic Performance of Simple Nonfused Ring Electron Acceptors.

Solving the contradiction between good solubility and dense packing is a challenge in designing high-performance nonfullerene acceptors. Herein, two simple nonfused ring electron acceptors (o-AT-2Cl and m-AT-2Cl) carrying ortho- or meta-substituted hexyloxy side chains can be facilely synthesized in only three steps. The two ortho-substituted phenyl side chains in o-AT-2Cl cannot freely rotate due to a big steric hindrance, which endows the acceptor with good solubility. Moreover, o-AT-2Cl displays a more ordered packing than m-AT-2Cl as revealed by the absorption measurement. When blended with polymer donor D18 for the fabrication of organic solar cells (OSCs), o-AT-2Cl-based devices exhibit a favorable morphology, more efficient exciton dissociation, and better charge transport. Consequently, the optimal OSCs based on D18:o-AT-2Cl exhibit a power conversion efficiency (PCE) of 12.8%, which is significantly higher than the moderate PCE (7.66%) for D18:m-AT-2Cl-based devices. Remarkably, o-AT-2Cl shows a higher figure-of-merit value compared with classic high-efficiency fused ring electron acceptors. As a result, our research succeeds in obtaining nonfused ring acceptors with cost-effective photovoltaic performance and provides a valuable experience for simultaneously improving solubility as well as ensuring ordered packing of acceptors through regulating the steric hindrance via changing the position of substituents.

Whole cell of pure Clostridium butyricum CBT-1 from anaerobic bioreactor effectively hydrolyzes agro-food waste into biohydrogen.

Recycling organic waste and converting them into renewable energy are a promising route for environment protection and effective biochemical reactions suitable for industrial hydrogen synthesis. This study targeted to isolate a pure anaerobic culture with potential to hydrolyze different biomass and production of biohydrogen. For this, a sample of full-scale anaerobic digester, fed with a multicomponent solid, was inoculated on Reinforced Clostridial Medium (RCM) in strict anaerobic conditions. An anaerobic Clostridium butyricum CBT-1 strain was isolated, identified from morphological and 16S rRNA sequence. The CBT-1 culture expressed amylase, cellulase and peroxidases activities. The strain exhibited visual decolorization of both Azure B and crystal violet dyes. In batch fermentation experiment, the CBT-1 produced highest of 3.06, 2.67 and 2.46 mol/mol H2 yield from glucose, starch and cellulose respectively, whereas, the CBT-1 showed low 0.43 mol H2/mol of substrate from untreated rice straw due to lignin in compact structure and comparatively high H2 yield of 1.91 and 2.01 mol H2/mol of substrate rice straw hydrolysate and kitchen food waste (KFWS) respectively. The cumulative volumetric yield of H2 was 358.15, 300.8 and 294.5NmL/gSub from glucose, starch and cellulose respectively. Similarly, the cumulative H2 volume was 76.7, 184.4, 237.2 NmL/gVS from untreated rice straw, rice straw hydrolysate and kitchen food waste. This study emphasizes the prospects to find similar robust anaerobic culture for hydrolyzing complex biomass. Such strains could be used as standard co-inoculum for biohydrogen obtaining and as the biocatalyst for commercial scale applications.

Chemical looping steam reforming of glycerol for hydrogen production over NiO-Fe2O3/Al2O3 oxygen carriers.

Fe-based oxygen carriers (OCs) are widely used in chemical looping steam reforming (CLSR) due to excellent resistance to carbon buildup, low toxicity, and high activity. In this study, a type of nano NiO-Fe2O3/Al2O3 Fe-based OC that can easily be reduced by fuels and re-oxidized by air was developed for use in glycerol CLSR. It was synthesized by co-precipitation and impregnation. Based on the quadratic regression orthogonal model, a quadratic polynomial function was established to investigate the effects of temperature (T), water/carbon ratio (S/C), and loading (M) on hydrogen content (HL) and hydrogen selectivity (S). The OCs were characterized by XRD, XPS, SEM/EDX-mapping, TEM, and H2-TPR to determine their physicochemical properties. XPS shows the Fe phase highly interacted with the Al2O3 supporting matrix by forming Fe aluminates in NiO-Fe2O3/Al2O3. The S (85.33%) and HL (78.41%) were obtained under the optimal conditions T = 600 °C, S/C = 1.0 mol mol-1 and M = 0. A hydrogen content fluctuation within 4% was obtained under T = 700 °C, S/C = 1.0 mol mol-1, and M = 2.5%, which means the cycle stability is perfect because of the addition of Ni. This study provides a basis for the development of efficient oxygen carriers in the CLSR system.

Molecular-Shape-Controlled Nonfused Ring Electron Acceptors for High-Performance Organic Solar Cells with Tunable Phase Morphology.

Two nonfused ring electron acceptors (NFREAs), BTh-OC8-2F and DTh-OC8-2F, with different molecular shapes are designed and synthesized. Both acceptors can form planar molecular shapes by the assistance of S···O intramolecular interactions. Differently, BTh-OC8-2F, with a linear molecular backbone and two trans-arranged side chains at the core unit, exhibits much stronger crystallinity than DTh-OC8-2, with a C-shape molecular shape and two cis-arranged steric side chains at the core unit. Thus, the DTh-OC8-2F based blend film displays a better nanoscale phase separation, more suppressed charge recombination, more efficient exciton dissociation, and lower nonradiative energy loss. Organic solar cells based on DTh-OC8-2F can deliver a power conversion efficiency of 14.13%, which is much higher than BTh-OC8-2F based ones (11.95%) and is also one of the highest values reported for organic solar cells based on NFREAs.

Ultrafast Carrier Dynamics of Non-fullerene Acceptors with Different Planarity: Impact of Steric Hindrance.

Most high-performance non-fullerene acceptors are of the acceptor-donor-acceptor (A-D-A)-type structure. Under photoexcitation, the intramolecular charge transfer effect on the A-D-A framework results in a large dipole moment change, facilitating the efficient generation of charge carriers. Achieving more efficient intramolecular charge transfer by adjusting the molecular structure is one of the current research ideas. Recently, we found that the power conversion efficiency can be improved from 4.41 to 13.13% by tuning the planarity of the non-fused ring electron acceptor backbone through steric hindrance of lateral substituents. We found that the planar backbone can effectively improve the intramolecular charge transfer, which has a great influence on the power conversion efficiency of the device. Our results demonstrate that charge transfer dynamics can be controlled by optimizing steric hindrance, which plays a crucial role in the photovoltaic performance of organic solar cells.

Design and Experimental Research of 3-RRS Parallel Ankle Rehabilitation Robot.

The ankle is a crucial joint that supports the human body weight. An ankle sprain will adversely affect the patient's daily life, so it is of great significance to ensure its strength. To help patients with ankle dysfunction to carry out effective rehabilitation training, the bone structure and motion mechanism of the ankle were analyzed in this paper. Referring to the configuration of the lower-mobility parallel mechanism, a 3-RRS (R and S denote revolute and spherical joint respectively) parallel ankle rehabilitation robot (PARR) was proposed. The robot can realize both single and compound ankle rehabilitation training. The structure of the robot was introduced, and the kinematics model was established. The freedom of movement of the robot was analyzed using the screw theory, and the robot kinematics were analyzed using spherical analytics theory. A circular composite rehabilitation trajectory was planned, and the accuracy of the kinematics model was verified by virtual prototype simulation. The Multibody simulation results show that the trajectory of the target point is basically the same as the expected trajectory. The maximum trajectory error is about 2.5 mm in the simulation process, which is within the controllable range. The experimental results of the virtual prototype simulation show that the maximum angular deflection error of the three motors is 2° when running a circular trajectory, which meets the experimental requirements. Finally, a control strategy for passive rehabilitation training was designed, and the effectiveness of this control strategy was verified by a prototype experiment.

Designing High-Performance Nonfused Ring Electron Acceptors via Synergistically Adjusting Side Chains and Electron-Withdrawing End-Groups.

Three nonfused ring electron acceptors, Hexyl-0F, Isopropyl-0F, and Isopropyl-2F, are designed and synthesized. Unlike Hexyl-0F, Isopropyl-0F with two sterically hindered 2,4,6-triisopropyl-phenyl groups is highly soluble, which provides a good opportunity for solution processability. Compared with Isopropyl-0F, Isopropyl-2F with fluorinated end-groups exhibits red-shifted absorption. Due to these synergistic adjustment, Isopropyl-2F-based devices displayed a high power conversion efficiency of 12.55%, higher than that of Isopropyl-0F (9.49%). The result demonstrates that the introduction of large steric substituents in the π-bridge units and electron-withdrawing end-groups plays a positive role in the construction of high-efficiency nonfused ring electron acceptors.

Stiffness Analysis of Parallel Cable-Driven Upper Limb Rehabilitation Robot.

This paper studies the stiffness of the parallel cable-driven upper limb rehabilitation robot (PCUR). Firstly, it was derived that the static stiffness expression of the PCUR was composed of platform pose stiffness KT and cable pose stiffness KS. It indicated that the static stiffness of the PCUR was related to the cable tension, the arrangement of the cable, and the cable stiffness. Secondly, a simulation model in MATLAB/Simscape Multibody was built. Cable tension was applied to make the moving platform in a static equilibrium state. The stiffness of the PCUR and the external force on the moving platform were changed, and the motion characteristics of the moving platform were obtained. Finally, the position changes of the moving platform under different external forces were analyzed, and the motion laws of the moving platform under different stiffnesses were summarized.

Chlorination Enabling a Low-Cost Benzodithiophene-Based Wide-Bandgap Donor Polymer with an Efficiency of over 17.

Three regioregular benzodithiophene-based donor-donor (D-D)-type polymers (PBDTT, PBDTT1Cl, and PBDTT2Cl) are designed, synthesized, and used as donor materials in organic solar cells (OSCs). Because of the weak intramolecular charge-transfer effect, these polymers exhibit large optical bandgaps (>2.0 eV). Among these three polymers, PBDTT1Cl exhibits more ordered and closer molecular stacking, and its devices demonstrate higher and more balanced charge mobilities and a longer charge-separated state lifetime. As a result of these comprehensive benefits, PBDTT1Cl-based OSCs give a very impressive power conversion efficiency (PCE) of 17.10% with a low nonradiative energy loss (0.19 eV). Moreover, PBDTT1Cl also possesses a low figure-of-merit value and good universality to match with different acceptors. This work provides a simply and efficient strategy to design low-cost high-performance polymer donor materials.

Anti-inflammatory and antibacterial activities of Pyrrosia petiolosa ethyl acetate (PPEAE) against Staphylococcus aureus in mice.

P. petiolosa as a typical Chinese herbal medicine has been generally utilized as Chinese native medicine formulation for treatment of chronic bronchitis, bronchial asthma and pneumoconiosis. The objective of this study was to evaluate the anti-inflammatory and antibacterial activities of P. petiolosa ethyl acetate extract (PPEAE) against S. aureusin mice. In our study, mice were infected pneumonia by S. aureus, colonization of S. aureus in lung tissue was calculated and the number of white blood cells (WBC) in blood was measured. Meanwhile, the hematoxylin-eosin staining (H&E) was observed and the Real-time PCR was employed to determine the relative mRNA expression. The results showed that, after treated with PPEAE the wet/dry (W/D) weight ratio and the number of WBC decreased dramatically, the number of S. aureus was significantly reduced. Furthermore, H&E staining showed that PPEAE obviously relieved the inflammation of infected mice and real-time PCR results indicated that PPEAE significantly down regulated the inflammatory iNOS, TNF-α and up regulated the anti-inflammatory HO-1 mRNA. In summary, our study revealed that application of crude product PPEAE had prominent antibacterial activity against S. aureus. PPEAE significantly reduced the biomass of S. aureus and effectively relieved the inflammation of S. aureus-induced pneumonia.

miR-155 induces endothelial cell apoptosis and inflammatory response in atherosclerosis by regulating Bmal1.

Atherosclerosis is the leading cause of death from vascular diseases worldwide, and endothelial cell (EC) dysfunction is the key cause of atherosclerosis. miR-155 was found to induce endothelial injury and to trigger atherosclerosis. In addition, brain and muscle ARNT-like protein-1 (Bmal1) has been found to be closely related to EC function. Therefore, the present study aimed to explore the mechanism underlying the regulation of Bmal1 by miR-155 in the induction of EC apoptosis and inflammatory response in atherosclerosis. The atherosclerosis model in apolipoprotein E (ApoE)- / - mice was established. miR-155 and Bmal1 expression was quantified by RT-qPCR and western blot analysis, respectively. The role of miR-155 and Bmal1 in atherosclerosis was evaluated through changes in cardiac function, plaque area, cardiomyocyte apoptosis, and inflammatory factor levels in mice. Moreover, the regulatory relationship between them was identified by dual-luciferase reporter gene assay to explore the mechanism of action of miR-155. After the modeling, the expression of miR-155 was upregulated and Bmal1 was downregulated in aorta, and there was a significant linear correlation between them. Upregulation of miR-155 increased the atherosclerotic plaque area, cell apoptosis, total cholesterol (TC) and triglyceride (TG), as well as weakened aortic diastolic function. However, opposite changes occurred after downregulation of miR-155 or an increase in Bmal1. In addition, the microRNA.org website predicted that there were targeted binding sites between miR-155 and Bmal1, which was verified with a dual-luciferase reporter gene assay. miR-155 was able to inhibit the expression by targeting Bmal1. Moreover, a rescue experiment showed that Bmal1 hindered the promotion of miR-155 in regards to atherosclerosis. In conclusion, miR-155 induces EC apoptosis and inflammatory response, weakens aortic diastolic function, and promotes the progression of atherosclerosis through targeted inhibition of Bmal1.