Multi-omics reveal mechanisms of high enteral starch diet mediated colonic dysbiosis via microbiome-host interactions in young ruminant.

BACKGROUND: Although rumen development is crucial, hindgut undertakes a significant role in young ruminants' physiological development. High-starch diet is usually used to accelerate rumen development for young ruminants, but always leading to the enteral starch overload and hindgut dysbiosis. However, the mechanism behind remains unclear. The combination of colonic transcriptome, colonic luminal metabolome, and metagenome together with histological analysis was conducted using a goat model, with the aim to identify the potential molecular mechanisms behind the disrupted hindgut homeostasis by overload starch in young ruminants. RESULT: Compared with low enteral starch diet (LES), high enteral starch diet (HES)-fed goats had significantly higher colonic pathology scores, and serum diamine oxidase activity, and meanwhile significantly decreased colonic mucosal Mucin-2 (MUC2) protein expression and fecal scores, evidencing the HES-triggered colonic systemic inflammation. The bacterial taxa Prevotella sp. P4-67, Prevotella sp. PINT, and Bacteroides sp. CAG:927, together with fungal taxa Fusarium vanettenii, Neocallimastix californiae, Fusarium sp. AF-8, Hypoxylon sp. EC38, and Fusarium pseudograminearum, and the involved microbial immune pathways including the "T cell receptor signaling pathway" were higher in the colon of HES goats. The integrated metagenome and host transcriptome analysis revealed that these taxa were associated with enhanced pathogenic ability, antigen processing and presentation, and stimulated T helper 2 cell (TH2)-mediated cytokine secretion functions in the colon of HES goats. Further luminal metabolomics analysis showed increased relative content of chenodeoxycholic acid (CDCA) and deoxycholic acid (DCA), and decreased the relative content of hypoxanthine in colonic digesta of HES goats. These altered metabolites contributed to enhancing the expression of TH2-mediated inflammatory-related cytokine secretion including GATA Binding Protein 3 (GATA3), IL-5, and IL-13. Using the linear mixed effect model, the variation of MUC2 biosynthesis explained by the colonic bacteria, bacterial functions, fungi, fungal functions, and metabolites were 21.92, 20.76, 19.43, 12.08, and 44.22%, respectively. The variation of pathology scores explained by the colonic bacterial functions, fungal functions, and metabolites were 15.35, 17.61, and 57.06%. CONCLUSIONS: Our findings revealed that enteral starch overload can trigger interrupted hindgut host-microbiome homeostasis that led to impaired mucosal, destroyed colonic water absorption, and TH2-mediated inflammatory process. Except for the colonic metabolites mostly contribute to the impaired mucosa, the nonnegligible contribution from fungi deserves more future studies focused on the fungal functions in hindgut dysbiosis of young ruminants. Video Abstract.

Coordination between circadian neural circuit and intracellular molecular clock ensures rhythmic activation of adult neural stem cells.

The circadian clock throughout the day organizes the activity of neural stem cells (NSCs) in the dentate gyrus (DG) of adult hippocampus temporally. However, it is still unclear whether and how circadian signals from the niches contribute to daily rhythmic variation of NSC activation. Here, we show that norepinephrinergic (NEergic) projections from the locus coeruleus (LC), a brain arousal system, innervate into adult DG, where daily rhythmic release of norepinephrine (NE) from the LC NEergic neurons controlled circadian variation of NSC activation through ß3-adrenoceptors. Disrupted circadian rhythmicity by acute sleep deprivation leads to transient NSC overactivation and NSC pool exhaustion over time, which is effectively ameliorated by the inhibition of the LC NEergic neuronal activity or ß3-adrenoceptors-mediated signaling. Finally, we demonstrate that NE/ß3-adrenoceptors-mediated signaling regulates NSC activation through molecular clock BMAL1. Therefore, our study unravels that adult NSCs precisely coordinate circadian neural circuit and intrinsic molecular circadian clock to adapt their cellular behavior across the day.

Dual Polymerized Y-Acceptors of Distinct-Dimensionality Create Neuron-Like Interpenetrating Hierarchical Network towards Efficient and Stable All-Polymer Solar Cells.

All-polymer solar cells have garnered particular attention thanks to their superior thermal, photo, and mechanical stabilities for large-scale manufacturing, yet the performance enhancement remains largely restrained by inherent morphological challenges of the bulk-heterojunction active layer. Herein, a 3D Y-branched polymerized small-molecule acceptor named PYBF, characteristic of high molecular weight and glass transition temperature, is designed and synthesized by precisely linking C3h-symmetric benzotrifuran with Y6 acceptors. In comparison to the benchmark thiophene-bridged linear PYIT acceptor, an optical blue-shift absorption is observed for PYBF yet a slightly higher power conversion efficiency (PCE) of 15.7% (vs 15.14%) is obtained when paired with polymer donor PM6, which benefit from the more crystalline and face-on-oriented PYBF domains. However, the star-like bulky structure of PYBF results in the nucleation-growth dominant phase-separation in polymeric blends, which generates stumpy droplet-like acceptor fibrils and impairs the continuity of acceptor phases. This issue is however surprisingly resolved by incorporating a small amount of PYIT, which leads to the formation of the more interconnective neuron-like dual-acceptor domains by long-chain entanglements of linear acceptors and alleviates bimolecular recombination. Thus, the champion device realizes a respectable PCE of up to ≈17% and importantly exhibits thermal and storage stabilities superior to the linear counterpart.

The Self-Assembly Soluplus Nanomicelles of Nobiletin in Aqueous Medium Based on Solid Dispersion and Their Increased Hepatoprotective Effect on APAP-Induced Acute Liver Injury.

Purpose: APAP-induced liver injury (AILI) is a common cause of acute liver failure (ALF). Nobiletin (NOB) is a potential hepatoprotective agent for the treatment of APAP-induced liver injury. However, the poor solubility and low bioavailability of NOB hinders its application. In this study, a novel self-assembly nano-drug delivery system of nobiletin (solid dispersion of NOB, termed as NOB/SD) was developed based on solid dispersion technology to improve the bioavailability and hepatoprotective ability of NOB for APAP-induced liver injury therapy. Methods: The optimized NOB/SD system was constructed using the amphiphilic copolymers of Soluplus and PVP/VA 64 via hot melt extrusion technology (HME). NOB/SD was characterized by solubility, physical interaction, drug release behavior, and stability. The bioavailability and hepatoprotective effects of NOB/SD were evaluated in vitro and in vivo. Results: NOB/SD maintained NOB in matrix carriers in a stable amorphous state, and self-assembled NOB-loaded nanomicelles in water. Nanostructures based on solid dispersion technology exhibited enhanced solubility, improved release behavior, and promoted cellular uptake and anti-apoptosis in vitro. NOB/SD displayed significantly improved bioavailability in healthy Sprague Dawley (SD) rats in vivo. Furthermore, NOB/SD alleviated the APAP-induced liver injury by improving anti-oxidative stress with reactive oxygen species (ROS) scavenging and nuclear factor erythroid 2-related factor 2 (Nrf2) activation. Conclusion: These results suggested that NOB/SD could be considered as a promising hepatoprotective nano-drug delivery system for attenuating APAP-induced acute liver injury with superior bioavailability and efficient hepatoprotection, which might provide an effective strategy for APAP-induced acute liver injury prevention and treatment.

Numerical simulation of deposition of drifts and salt from multiple super-large seawater cooling towers.

A three-dimensional CFD simulation model was established to study the characteristics of flow, drifts and salt deposition from 6 super-large seawater cooling towers in a power station. In the model, site meteorological data, design parameters of cooling tower, general layout, environmental characteristics, are considered. The results show that: (1) when the wind direction is parallel to the towers, the streams overlap, reducing deposition of drifts and salt onto the ground. (2) The drifts with particle size greater than 550 µm cannot float out of cooling towers. (3) In normal operation of 6 such cooling towers, the resulting salt deposition will not cause serious damage to plants.

Potential roles of the rectum keystone microbiota in modulating the microbial community and growth performance in goat model.

BACKGROUND: Ruminal microbiota in early life plays critical roles in the life-time health and productivity of ruminant animals. However, understanding of the relationship between gut microbiota and ruminant phenotypes is very limited. Here, the relationship between the rectum microbiota, their primary metabolites, and growth rate of a total of 76 young dairy goats (6-month-old) were analyzed, and then 10 goats with the highest or lowest growth rates respectively were further compared for the differences in the rectum microbiota, metabolites, and animal's immune parameters, to investigate the potential mechanisms by which the rectum microbiota contributes to the health and growth rate. RESULTS: The analysis of Spearman correlation and microbial co-occurrence network indicated that some keystone rectum microbiota, including unclassified Prevotellaceae, Faecalibacterium and Succinivibrio, were the key modulators to shape the rectum microbiota and closely correlated with the rectum SCFA production and serum IgG, which contribute to the health and growth rate of young goats. In addition, random forest machine learning analysis suggested that six bacterial taxa in feces could be used as potential biomarkers for differentiating high or low growth rate goats, with 98.3% accuracy of prediction. Moreover, the rectum microbiota played more important roles in gut fermentation in early life (6-month-old) than in adulthood stage (19-month-old) of goats. CONCLUSION: We concluded that the rectum microbiota was associated with the health and growth rate of young goats, and can be a focus on the design of the early-life gut microbial intervention.

Low rumen degradable starch promotes the growth performance of goats by increasing protein synthesis in skeletal muscle via the AMPK-mTOR pathway.

Since starch digestion in the small intestine provides more energy than digestion in the rumen of ruminants, reducing dietary rumen degradable starch (RDS) content is beneficial for improving energy utilization of starch in ruminants. The present study tested whether the reduction of rumen degradable starch by restricting dietary corn processing for growing goats could improve growth performance, and further investigated the possible underlying mechanism. In this study, twenty-four 12-wk-old goats were selected and randomly allocated to receive either a high RDS diet (HRDS, crushed corn-based concentrate, the mean of particle sizes of corn grain = 1.64 mm, n = 12) or a low RDS diet (LRDS, non-processed corn-based concentrate, the mean of particle sizes of corn grain >8 mm, n = 12). Growth performance, carcass traits, plasma biochemical indices, gene expression of glucose and amino acid transporters, and protein expression of the AMPK-mTOR pathway were measured. Compared to the HRDS, LRDS tended to increase the average daily gain (ADG, P = 0.054) and decreased the feed-to-gain ratio (F/G, P < 0.05). Furthermore, LRDS increased the net lean tissue rate (P < 0.01), protein content (P < 0.05) and total free amino acids (P < 0.05) in the biceps femoris (BF) muscle of goats. LRDS increased the glucose concentration (P < 0.01), but reduced total amino acid concentration (P < 0.05) and tended to reduce blood urea nitrogen (BUN) concentration (P = 0.062) in plasma of goats. The mRNA expression of insulin receptors (INSR), glucose transporter 4 (GLUT4), L-type amino acid transporter 1 (LAT1) and 4F2 heavy chain (4F2hc) in BF muscle, and sodium-glucose cotransporters 1 (SGLT1) and glucose transporter 2 (GLUT2) in the small intestine were significantly increased (P < 0.05) in LRDS goats. LRDS also led to marked activation of p70-S6 kinase (S6K) (P < 0.05), but lower activation of AMP-activated protein kinase (AMPK) (P < 0.05) and eukaryotic initiation factor 2α (P < 0.01). Our findings suggested that reducing the content of dietary RDS enhanced postruminal starch digestion and increased plasma glucose, thereby improving amino acid utilization and promoting protein synthesis in the skeletal muscle of goats via the AMPK-mTOR pathway. These changes may contribute to improvement in growth performance and carcass traits in LRDS goats.

One-year Efficacy of the Defocus Incorporated Multiple Segment Lens in Chinese Myopic Children.

SIGNIFICANCE: These data demonstrate that defocus incorporated multiple segment (DIMS) lens reduces myopia progression in children during the first year of use. PURPOSE: This study aimed to investigate the efficacy of DIMS myopia control spectacle lens in Chinese myopic children aged 6 to 15 years. METHODS: This is a retrospective study of 1-year longitudinal data. A total of 180 Chinese myopic children were selected from patients at Zhongshan Ophthalmic Center, Sun Yat-sen University, from February 2018 to January 2021. One group consisted of 90 children aged 6 to 15 years, with spherical equivalent refraction -0.50 to -7.75 D (-3.82 ± 1.57 D) and fitted with the DIMS lens. The other group consisted of 90 children fitted with single-vision spectacle lenses and matched with the DIMS group for age, sex, refraction, and progression of myopia in the previous year. One-year myopia progression was measured retrospectively in two groups. Unpaired t test was used to compare the myopia progression between the DIMS group and the control group. Pearson correlation was used to explore the relationship between myopia progression, age, and baseline refraction. RESULTS: After 1 year of DIMS lens wear, myopia progression was significantly lower in the DIMS group (-0.51 ± 0.50 vs. -0.85 ± 0.51 D, P < .001). Myopia progression was positively correlated with age in both groups. The difference between the DIMS and control groups was more pronounced for children aged 10 to 15 years than for children aged 6 to 9 years. CONCLUSIONS: This study confirms that the DIMS lens reduces myopia progression during the first year of use. Efficacy seems to increase with age.

Review of glucose oxidase as a feed additive: production, engineering, applications, growth-promoting mechanisms, and outlook.

The regulation and prohibition of antibiotics used as growth promoters (AGP) in the feed field are increasing because they cause antimicrobial resistance and drug residue issues and threaten community health. Recently, glucose oxidase (GOx) has attracted increasing interest in the feed industry as an alternative to antibiotics. GOx specifically catalyzes the production of gluconic acid (GA) and hydrogen peroxide (H2O2) by consuming molecular oxygen, and plays an important role in relieving oxidative stress, preserving health, and promoting animal growth. To expand the application of GOx in the feed field, considerable efforts have been made to mine new genetic resources. Efforts have also been made to heterologously overexpress relevant genes to reduce production costs and to engineer proteins by modifying enzyme properties, both of which are bottleneck problems that limit industrial feed applications. Herein, the: different sources, diverse biochemical properties, distinct structural features, and various strategies of GOx engineering and heterologous overexpression are summarized. The mechanism through which GOx promotes growth in animal production, including the improvement of antioxidant capacity, maintenance of intestinal microbiota homeostasis, and enhancement of gut function, are also systematically addressed. Finally, a new perspective is provided for the future development of GOx applications in the feed field.

Developing Y-Branched Polymer Acceptor with 3D Architecture to Reconcile Between Crystallinity and Miscibility Yielding >15% Efficient All-Polymer Solar Cells.

In all-polymer solar cells (all-PSCs), there remains such a dilemma that obtains good miscibility and crystallinity simultaneously. Herein a new family of Y-shape polymer acceptor, namely PYTT is developed, which is copolymerized from Y6 and benzotrithiophene units in three-way directions. Benefiting from its high-density end-chains and extended π-conjugation thanks to highly-branched 3D architecture, PYTT displays better organic solubility despite much higher molecular weights, larger crystallinity, and tighter π-stacking than the linear counterpart-PYT comprising Y6 and thiophene moieties, while showing identical optical absorption yet threefold higher photoluminescence intensity. In PYTT blend film with PM6 polymer donor, the interpenetrating nano-fibrillar structures are formed with well-intermixed polymeric domain sizes close to the exciton diffusion length, which is greatly conducive to exciton dissociation and charge transport in device. Consequently, PYTT-based all-PSCs exhibit all increased photovoltaic parameters, yielding a decent power conversion efficiency of 15.60%, which is ≈20% enhancement over PYT-based device, along with low nonradiative loss of 0.221 meV.

[Multi-channel contactless conductivity detection device for online detection of free-flow electrophoresis separation].

Free-flow electrophoresis (FFE) is an all-liquid-phase electrophoresis technique without any supporting media, which has both analytical and preparative functions. Compared to other electrophoresis techniques, FFE has been used for the separation of peptides, proteins, cells, and microorganisms due to its advantages of mild separation environment, high recovery, and sustainable separation. Both the online detection of the characteristic parameters for each component solution and the real-time control of the progress of the separation experiment are of considerable importance for the study of FFE separation. Since the existing FFE devices do not have the online detection function, there are obvious deficiencies in their practicability. The absence of online detection function not only made it impossible to track the progress of the separation experiment in real time, but also made it difficult to detect the properties of the component solutions, which still require offline testing after separation. In this study, a multi-channel capacitively coupled contactless conductivity detection (MC-C4D) device has been developed to solve this problem, and an automatic measurement software has also been developed. The MC-C4D device used a parallel time-sharing contactless conductivity detection technique. It consisted of several contactless conductivity detection modules arranged in parallel, which in turn consisted of a number of contactless conductivity cells that were switched on/off by analog multiplexers for detecting the conductivity of the solution flowing through the cells in real time. The number of cells was equal to the number of components of the FFE. The components were connected to each of the FFE flow channels, such that the MC-C4D device could be used to measure the conductivity of the solution flowing through each channel in parallel online. To verify the performance of the MC-C4D device, calibration was conducted by using potassium chloride (KCl) standard solutions on MC-C4D device. The experimental data showed that the detection range of MC-C4D was 0.015-2.5 mS/cm, and the limit of detection (LOD) was 0.002 mS/cm. The intra-day relative standard deviation (RSD, n=3) was 2.31%, the measurement relative error (RE) was 3.03%, and the measurement difference between channels was 1.60%. All these data validated that the device had the advantages of wide detection range, low LOD, good repeatability, high accuracy, and low variation between channels. The MC-C 4D device was also applied to reciprocating free-flow isoelectric focusing (RFFIEF) electrophoresis for real-time online detection of the conductivity of each component solution during protein focusing. At the start of isoelectric focusing, when the ions had not reached equilibrium loading in the electric field and the pH gradient had not yet been fully developed, there was little difference in conductivity between the different channels and the channel conductivity curve was relatively flat. As the experiment progressed, the proteins gradually started to enrich the anodic end. As the proteins accumulated towards the isoelectric point, their own net charge gradually decreased, and thus, the conductivity of the solution in the channels near the anodic region also decreased. Under sufficient isoelectric focusing, protein enrichment was evident. In the focusing region, the conductivity of the solution in the corresponding channel decreased further. There was also an increase in the conductivity of the solution in the corresponding channel due to the accumulation of ions near the electrode ends. These results showed that the MC-C4D device not only enabled real-time online detection of the conductivity of each component solution in FFE, but also aided in mastering the progress of separation experiment in RFFIEF, thus improving the practicality of the FFE device. Thus, the MC-C4D device, which had the advantages of good performance, small size, simple circuit system, easy installation and commissioning, and low cost, could play an important role in multi-channel measurement, online inspection, and process monitoring.

A facile online multi-gear capacitively coupled contactless conductivity detector for an automatic and wide range monitoring of high salt in HPLC.

Sensing the electrolyte solution or aqueous-organic mixture has attracted much interest in chemical separation, pharmaceutical engineering, bioprocess, and biochemical experiments. However, reports on online contactless sensor with automatic and wide range sensing of high content electrolyte have been rarely presented. Herein, a facile model and theory of online multi-gear capacitively coupled contactless conductivity detection (M-C4D) sensor was proposed using one excitation electrode and multiple detection electrodes. Further, the relevant digital computation based on the M-C4D theory was developed for parameter optimization: the electrode gap of 5-150 mm, inner radius of 0.25-0.75 mm, electrode length of 10-60 mm, and frequency of 40-250 kHz using MATLAB. To demonstrate the model, theory, and digital computation, liquid chromatography (LC) was chosen as the model of bioprocess, and the sensor was designed and used as an online sensing device for the automatic monitoring of high salt elution in LC. The experiments showed that (i) the detection results were in agreement with the digital data, validating the digital computation, theory, and model of M-C4D and (ii) the monitoring data of M-C4D were in agreement with those via the traditional meter, further validating the model and theory. Finally, the developed sensor was applied to the automated detection of high salt gradient in LC. In contrast to the currently used meters and C4D, the developed M-C4D sensor had the following merits: (i) facile and automatic online detection avoiding cumbersome manual switching of detector heads, (ii) fair linear range of 0.015-20 mS cm-1 (equivalently 0.1-159 mM KCl) that does not fit the range of traditional C4D, and (iii) fair accuracy of less than 1.50% relative error. All these results indicate that the developed model, theory, and sensor have potential for the process monitoring of high content electrolytes transfer in biochemical engineering and clinic pre-warning.

Achieving Efficient p-Type Organic Thermoelectrics by Modulation of Acceptor Unit in Photovoltaic π-Conjugated Copolymers.

π-Conjugated donor (D)-acceptor (A) copolymers have been extensively studied as organic photovoltaic (OPV) donors yet remain largely unexplored in organic thermoelectrics (OTEs) despite their outstanding mechanical bendability, solution processability and flexible molecular design. Importantly, they feature high Seebeck coefficient (S) that are desirable in room-temperature wearable application scenarios under small temperature gradients. In this work, the authors have systematically investigated a series of D-A semiconducting copolymers possessing various electron-deficient A-units (e.g., BDD, TT, DPP) towards efficient OTEs. Upon p-type ferric chloride (FeCl3 ) doping, the relationship between the thermoelectric characteristics and the electron-withdrawing ability of A-unit is largely elucidated. It is revealed that a strong D-A nature tends to induce an energetic disorder along the π-backbone, leading to an enlarged separation of the transport and Fermi levels, and consequently an increase of S. Meanwhile, the highly electron-deficient A-unit would impair electron transfer from D-unit to p-type dopants, thus decreasing the doping efficiency and electrical conductivity (σ). Ultimately, the peak power factor (PF) at room-temperature is obtained as high as 105.5 µW m-1 K-2 with an outstanding S of 247 µV K-1 in a paradigm OPV donor PBDB-T, which holds great potential in wearable electronics driven by a small temperature gradient.

P3HT-Based Organic Solar Cells with a Photoresponse to 1000 nm Enabled by Narrow Band Gap Nonfullerene Acceptors with High HOMO Levels.

Three narrow band gap (NBG) acceptors, namely, TTDTC-0F, TTDTC-2F, and TTDTC-4F, were synthesized by introducing a strong electron-donating unit as the central core. The enhanced intramolecular charge transfer endows the three acceptors with high-lying highest occupied molecular orbitals (HOMOs) of ∼-5.20 eV and ultranarrow band gaps (∼1.25 eV). When blended with poly(3-hexylthiophene) (P3HT), all organic solar cells (OSCs) exhibited a broad photoresponse from 300 to ∼1000 nm. Among them, P3HT:TTDTC-4F-based devices achieved the highest efficiency of 7.81% with a prominent Jsc exceeding 22 mA·cm-2. This study demonstrates that the conjugated molecules with high HOMOs can also function as acceptor materials for P3HT-based OSCs, which opens a window to increase PCEs of P3HT-based OSCs in the future to the level of the devices based on the current state-of-the-art polymer donor materials.

Implementing an intermittent spin-coating strategy to enable bottom-up crystallization in layered halide perovskites.

Two-dimensional halide perovskites (2D PVSKs) have drawn tremendous attentions owing to their outstanding ambient stability. However, the random orientation of layered crystals severely impedes the out-of-plane carrier transport and limits the solar cell performance. An in-depth understanding coupled with an effective control of the crystallization in 2D PVSKs is the crux for highly efficient and durable devices. In this contribution, we accidentally discovered that the crystallization of 2D PVSKs can be effectively regulated by so-called 'intermittent spin-coating (ISC)' process. Combined analyses of in(ex)-situ grazing-incidence wide-angle X-ray scattering with time-of-flight secondary ion mass spectrometry distinguish the interface initialized bottom-up crystallization upon ISC treatment from the bi-directional one in the conventional spin-coating process, which results in significantly enhanced crystal orientation and thus facilitated carrier transport as confirmed by both electrical measurements and ultrafast spectroscopies. As a result, the p-i-n architecture planar solar cells based on ISC fabricated paradigm PEA2MA3Pb4I13 deliver a respectable efficiency of 11.2% without any treatment, which is three-fold improvement over their spin-coated counterparts and can be further boosted up to 14.0% by NH4Cl addition, demonstrating the compatibility of ISC method with other film optimization strategies.

Fluorination Enables Tunable Molecular Interaction and Photovoltaic Performance in Non-Fullerene Solar Cells Based on Ester-Substituted Polythiophene.

Owing to the advantages of low synthetic cost and high scalability of synthesis, polythiophene and its derivatives (PTs) have been of interest in the community of organic photovoltaics (OPVs). Nevertheless, the typical efficiency of PT based photovoltaic devices reported so far is much lower than those of the prevailing push-pull type conjugated polymer donors. Recent studies have underscored that the excessively low miscibility between PT and nonfullerene acceptor is the major reason accounting for the unfavorable active layer morphology and the inferior performance of OPVs based on a well-known PT, namely PDCBT-Cl and a non-halogenated nonfullerene acceptor IDIC. How to manipulate the miscibility between PT and acceptor molecule is important for further improving the device efficiency of this class of potentially low-cost blend systems. In this study, we introduced different numbers of F atoms to the end groups of IDIC to tune the intermolecular interaction of the hypo-miscible blend system (PDCBT-Cl:IDIC). Based on calorimetric, microscopic, and scattering characterizations, a clear relationship between the number of F atoms, miscibility, and device performance was established. With the increased number of F atoms in IDIC, the resulting acceptors exhibited enhanced miscibility with PDCBT-Cl, and the domain sizes of the blend films were reduced substantially. As a result, distinctively different photovoltaic performances were achieved for these blend systems. This study demonstrates that varying the number of F atoms in the acceptors is a feasible way to manipulate the molecular interaction and the film morphology toward high-performance polythiophene:nonfullerene based OPVs.

The Rab7 effector WDR91 promotes autophagy-lysosome degradation in neurons by regulating lysosome fusion.

The effectors of the Rab7 small GTPase play multiple roles in Rab7-dependent endosome-lysosome and autophagy-lysosome pathways. However, it is largely unknown how distinct Rab7 effectors coordinate to maintain the homeostasis of late endosomes and lysosomes to ensure appropriate endolysosomal and autolysosomal degradation. Here we report that WDR91, a Rab7 effector required for early-to-late endosome conversion, is essential for lysosome function and homeostasis. Mice lacking Wdr91 specifically in the central nervous system exhibited behavioral defects and marked neuronal loss in the cerebral and cerebellar cortices. At the cellular level, WDR91 deficiency causes PtdIns3P-independent enlargement and dysfunction of lysosomes, leading to accumulation of autophagic cargoes in mouse neurons. WDR91 competes with the VPS41 subunit of the HOPS complex, another Rab7 effector, for binding to Rab7, thereby facilitating Rab7-dependent lysosome fusion in a controlled manner. WDR91 thus maintains an appropriate level of lysosome fusion to guard the normal function and survival of neurons.

Direct Arylation Polycondensation toward Water/Alcohol-Soluble Conjugated Polymers: Influence of Side Chain Functional Groups.

Direct arylation of 2,7-dibromofluorene with n-octyl, 6-diethoxylphosphorylhexyl, 6-(N,N-diethylamino)hexyl or 6-bromohexyl side chains and 1,2,4,5-tetrafluorobenzene (TFB) were conducted to investigate the effect of side chain functional groups on the coupling, and the resulting TFB-substituted fluorene derivatives were used as C-H monomers for the synthesis of water/alcohol soluble conjugated polymers (WSCPs) by direct arylation polycondensation (DArP). The direct arylation and DArP of the monomers carrying phosphonate and amino groups went on smoothly in typical DArP conditions, that is, Pd(OAc)2/PtBu2Me-HBF4/base/DMAc and Pd2(dba)3·CHCl3/P(o-MeOPh)3/pivalic acid/base/THF, and high molecular weight polymers with these groups were successfully synthesized. However, for fluorene-monomers with bromohexyl side chains, the target products could not be obtained from the above conditions but could be prepared in the absence of carboxylic acid additives in low polar solvents. With the above DArP-made polymers as cathode interfacial layers, high performance organic solar cells (OSCs) were successfully fabricated.

Significance of thermodynamic interaction parameters in guiding the optimization of polymer:nonfullerene solar cells.

Polymer solar cells (PSCs) based on polymer donors and nonfullerene small molecule acceptors are a very attractive technology for solar energy conversion, and their performance is heavily determined by film morphology. It is of considerable interest to reveal instructive morphology-performance relationships of these blends. This feature article discusses the recent advances in analysing the morphology formation of nonfullerene PSCs with an effective polymer thermodynamic quantity, i.e., Flory-Huggins interaction parameter χ. In particular, guidelines of high and low χ systems are summarized. The fundamental understanding of χ and its correlations to film morphology and photovoltaic device parameters is of utmost relevance for providing essential material design criteria, establishing suitable morphology processing guidelines, and thus advancing the practical applications of PSCs based on nonfullerene acceptors.

A Brain Signaling Framework for Stress-Induced Depression and Ketamine Treatment Elucidated by Phosphoproteomics.

Depression is a common affective disorder characterized by significant and persistent low mood. Ketamine, an N-methyl-D-aspartate receptor (NMDAR) antagonist, is reported to have a rapid and durable antidepressant effect, but the mechanisms are unclear. Protein phosphorylation is a post-translational modification that plays a crucial role in cell signaling. Thus, we present a phosphoproteomics approach to investigate the mechanisms underlying stress-induced depression and the rapid antidepressant effect of ketamine in mice. We analyzed the phosphoprotein changes induced by chronic unpredictable mild stress (CUMS) and ketamine treatment in two known mood control centers, the medial prefrontal cortex (mPFC) and the nucleus accumbens (NAc). We initially obtained >8,000 phosphorylation sites. Quantitation revealed 3,988 sites from the mPFC and 3,196 sites from the NAc. Further analysis revealed that changes in synaptic transmission-related signaling are a common feature. Notably, CUMS-induced changes were reversed by ketamine treatment, as shown by the analysis of commonly altered sites. Ketamine also induced specific changes, such as alterations in synapse organization, synaptic transmission, and enzyme binding. Collectively, our findings establish a signaling framework for stress-induced depression and the rapid antidepressant effect of ketamine.