Lactate-mediated medium-chain fatty acid production from expired dairy and beverage waste.

Fruits, vegetables, and dairy products are typically the primary sources of household food waste. Currently, anaerobic digestion is the most used bioprocess for the treatment of food waste with concomitant generation of biogas. However, to achieve a circular carbon economy, the organics in food waste should be converted to new chemicals with higher value than energy. Here we demonstrate the feasibility of medium-chain carboxylic acid (MCCA) production from expired dairy and beverage waste via a chain elongation platform mediated by lactate. In a two-stage fermentation process, the first stage with optimized operational conditions, including varying temperatures and organic loading rates, transformed expired dairy and beverage waste into lactate at a concentration higher than 900 mM C at 43 °C. This lactate was then used to produce >500 mM C caproate and >300 mM C butyrate via microbial chain elongation. Predominantly, lactate-producing microbes such as Lactobacillus and Lacticaseibacillus were regulated by temperature and could be highly enriched under mesophilic conditions in the first-stage reactor. In the second-stage chain elongation reactor, the dominating microbes were primarily from the genera Megasphaera and Caproiciproducens, shaped by varying feed and inoculum sources. Co-occurrence network analysis revealed positive correlations among species from the genera Caproiciproducens, Ruminococcus, and CAG-352, as well as Megasphaera, Bacteroides, and Solobacterium, indicating strong microbial interactions that enhance caproate production. These findings suggest that producing MCCAs from expired dairy and beverage waste via lactate-mediated chain elongation is a viable method for sustainable waste management and could serve as a chemical production platform in the context of building a circular bioeconomy.

Electrocoagulation enhanced gravity driven membrane bioreactor for advanced treatment of rural sewage.

The daily discharge of rural sewage in China occupies 30 % of the national wastewater discharge, and developing an energy-efficient, easy to operate, and decentralized rural sewage treatment technology becomes an important task. In this work, a novel rural sewage treatment technology, Electrocoagulation enhanced Gravity-Driven Membrane Bioreactor (EC-GDMBR) was exploited for the rural sewage treatment under long-term operation (160 days). Two EC-GDMBRs with various module structures of ceramic membrane (horizontal module and side module) not only displayed the desirable effluent quality, but also sustained the stable flux (8-13 LMH). The electrocoagulation, electrooxidation, biodegradation, and separation in EC-GDMBRs were able to synergistically remove the particle matter, organic (CODCr effluent <11.6 ± 1.2 mg/L) and nutrients (NH3-N effluent <0.1 mg/L, TN effluent <8.5 mg/L, TP effluent <0.05 mg/L). Besides, the high permeability of ceramic membrane and large porosity of biofilm on its surface improved the sustainability of stable flux during the long-term operation. Moreover, by analyzing bacterial abundance, Extracellular Polymeric Substances, Adenosine Tri-Phosphate and Confocal Laser Scanning Microscopy, a large number of microorganisms grew and accumulated on the carrier, as well as formed the biofilm (23.46-659.9 µm), while Nitrobacteria (1.6-4.1 %) and Nitrate (0.01-0.06 %) exited in the carrier biofilms, promoting the nitrogen removal. Compared with EC-GDMBR with side module of ceramic membrane, EC-GDMBR with horizontal module of ceramic membrane has advantages in flux behavior, organic/nutrient removal, microbial abundance/activity, abundance of nitrogen removal functional bacteria and water permeability of biofilm, because the ceramic membrane of horizontal module can promote the uniform growth of biofilm and improve the uniformity of flow penetration distribution. In general, the findings of this work verify the reliability of EC-GDMBR for the sustainable operation of wastewater treatment and improve its application value of rural sewage treatment.

Probing the functional hotspots inside protein hydrophobic pockets by in situ photochemical trifluoromethylation and mass spectrometry.

Due to the complex high-order structures and interactions of proteins within an aqueous solution, a majority of chemical functionalizations happen on the hydrophilic sites of protein external surfaces which are naturally exposed to the solution. However, the hydrophobic pockets inside proteins are crucial for ligand binding and function as catalytic centers and transporting tunnels. Herein, we describe a reagent pre-organization and in situ photochemical trifluoromethylation strategy to profile the functional sites inside the hydrophobic pockets of native proteins. Unbiased mass spectrometry profiling was applied for the characterization of trifluoromethylated sites with high sensitivity. Native proteins including myoglobin, trypsin, haloalkane dehalogenase, and human serum albumin have been engaged in this mild photochemical process and substantial hydrophobic site-specific and structure-selective trifluoromethylation substitutes are obtained without significant interference to their bioactivity and structures. Sodium triflinate is the only reagent required to functionalize the unprotected proteins with wide pH-range tolerance and high biocompatibility. This "in-pocket" activation model provides a general strategy to modify the potential binding pockets and gain essential structural insights into the functional hotspots inside protein hydrophobic pockets.

Rice LIKE EARLY STARVATION1 cooperates with FLOURY ENDOSPERM6 to modulate starch biosynthesis and endosperm development.

In cereal grains, starch is synthesized by the concerted actions of multiple enzymes on the surface of starch granules within the amyloplast. However, little is known about how starch-synthesizing enzymes access starch granules, especially for amylopectin biosynthesis. Here, we show that the rice (Oryza sativa) floury endosperm9 (flo9) mutant is defective in amylopectin biosynthesis, leading to grains exhibiting a floury endosperm with a hollow core. Molecular cloning revealed that FLO9 encodes a plant-specific protein homologous to Arabidopsis (Arabidopsis thaliana) LIKE EARLY STARVATION1 (LESV). Unlike Arabidopsis LESV, which is involved in starch metabolism in leaves, OsLESV is required for starch granule initiation in the endosperm. OsLESV can directly bind to starch by its C-terminal tryptophan (Trp)-rich region. Cellular and biochemical evidence suggests that OsLESV interacts with the starch-binding protein FLO6, and loss-of-function mutations of either gene impair ISOAMYLASE1 (ISA1) targeting to starch granules. Genetically, OsLESV acts synergistically with FLO6 to regulate starch biosynthesis and endosperm development. Together, our results identify OsLESV-FLO6 as a non-enzymatic molecular module responsible for ISA1 localization on starch granules, and present a target gene for use in biotechnology to control starch content and composition in rice endosperm.

DNA polymerase beta connects tumorigenicity with the circadian clock in liver cancer through the epigenetic demethylation of Per1.

The circadian-controlled DNA repair exhibits a strong diurnal rhythm. Disruption in circadian clock and DNA repair is closely linked with hepatocellular carcinoma (HCC) progression, but the mechanism remains unknown. Here, we show that polymerase beta (POLB), a critical enzyme in the DNA base excision repair pathway, is rhythmically expressed at the translational level in mouse livers. Hepatic POLB dysfunction dampens clock homeostasis, whereas retards HCC progression, by mediating the methylation of the 4th CpG island on the 5'UTR of clock gene Per1. Clinically, POLB is overexpressed in human HCC samples and positively associated with poor prognosis. Furthermore, the hepatic rhythmicity of POLB protein expression is orchestrated by Calreticulin (CALR). Our findings provide important insights into the molecular mechanism underlying the synergy between clock and food signals on the POLB-driven BER system and reveal new clock-dependent carcinogenetic effects of POLB. Therefore, chronobiological modulation of POLB may help to promote precise interventions for HCC.

FOXP3 recognizes microsatellites and bridges DNA through multimerization.

FOXP3 is a transcription factor that is essential for the development of regulatory T cells, a branch of T cells that suppress excessive inflammation and autoimmunity1-5. However, the molecular mechanisms of FOXP3 remain unclear. Here we here show that FOXP3 uses the forkhead domain-a DNA-binding domain that is commonly thought to function as a monomer or dimer-to form a higher-order multimer after binding to TnG repeat microsatellites. The cryo-electron microscopy structure of FOXP3 in a complex with T3G repeats reveals a ladder-like architecture, whereby two double-stranded DNA molecules form the two 'side rails' bridged by five pairs of FOXP3 molecules, with each pair forming a 'rung'. Each FOXP3 subunit occupies TGTTTGT within the repeats in a manner that is indistinguishable from that of FOXP3 bound to the forkhead consensus motif (TGTTTAC). Mutations in the intra-rung interface impair TnG repeat recognition, DNA bridging and the cellular functions of FOXP3, all without affecting binding to the forkhead consensus motif. FOXP3 can tolerate variable inter-rung spacings, explaining its broad specificity for TnG-repeat-like sequences in vivo and in vitro. Both FOXP3 orthologues and paralogues show similar TnG repeat recognition and DNA bridging. These findings therefore reveal a mode of DNA recognition that involves transcription factor homomultimerization and DNA bridging, and further implicates microsatellites in transcriptional regulation and diseases.

FoxP3 recognizes microsatellites and bridges DNA through multimerization.

FoxP3 is a transcription factor (TF) essential for development of regulatory T cells (Tregs), a branch of T cells that suppress excessive inflammation and autoimmunity 1-5 . Molecular mechanisms of FoxP3, however, remain elusive. We here show that FoxP3 utilizes the Forkhead domain--a DNA binding domain (DBD) that is commonly thought to function as a monomer or dimer--to form a higher-order multimer upon binding to T n G repeat microsatellites. A cryo-electron microscopy structure of FoxP3 in complex with T 3 G repeats reveals a ladder-like architecture, where two double-stranded DNA molecules form the two "side rails" bridged by five pairs of FoxP3 molecules, with each pair forming a "rung". Each FoxP3 subunit occupies TGTTTGT within the repeats in the manner indistinguishable from that of FoxP3 bound to the Forkhead consensus motif (FKHM; TGTTTAC). Mutations in the "intra-rung" interface impair T n G repeat recognition, DNA bridging and cellular functions of FoxP3, all without affecting FKHM binding. FoxP3 can tolerate variable "inter-rung" spacings, explaining its broad specificity for T n G repeat-like sequences in vivo and in vitro . Both FoxP3 orthologs and paralogs show similar T n G repeat recognition and DNA bridging. These findings thus reveal a new mode of DNA recognition that involves TF homo-multimerization and DNA bridging, and further implicates microsatellites in transcriptional regulation and diseases.

Absolute CO2 /Xenon Separation in Ultramicropore MOF for Anesthetic Gases Regeneration.

Xe is an ideal anesthetic gas, but it has not been widely used in practice due to its high cost and low output. Closed-circuit Xe recovery and recycling is an economically viable method to ensure adequate supply in medical use. Herein, we design an innovative way to recover Xe by using a stable fluorinated metal-organic framework (MOF) NbOFFIVE-1-Ni to eliminate CO2 from moist exhaled anesthetic gases. Unlike other Xe recovery MOFs with low Xe/CO2 selectivity (less than 10), NbOFFIVE-1-Ni could achieve absolute molecular sieve separation of CO2 /Xe with excellent CO2 selectivity (825). Mixed-gas breakthrough experiments assert the potential of NbOFFIVE-1-Ni as a molecular sieve adsorbent for the effective and energy-efficient removal of carbon dioxide with 99.16 % Xe recovery. Absolute CO2 /Xe separation in NbOFFIVE-1-Ni makes closed-circuit Xe recovery and recycling can be easily realized, demonstrating the potential of NbOFFIVE-1-Ni for important anesthetic gas regeneration under ambient conditions.

Mutations from patients with IPEX ported to mice reveal different patterns of FoxP3 and Treg dysfunction.

Mutations of the transcription factor FoxP3 in patients with "IPEX" (immune dysregulation, polyendocrinopathy, enteropathy, X-linked syndrome) disrupt regulatory T cells (Treg), causing an array of multiorgan autoimmunity. To understand the functional impact of mutations across FoxP3 domains, without genetic and environmental confounders, six human FOXP3 missense mutations are engineered into mice. Two classes of mutations emerge from combined immunologic and genomic analyses. A mutation in the DNA-binding domain shows the same lymphoproliferation and multiorgan infiltration as complete FoxP3 knockouts but delayed by months. Tregs expressing this mutant FoxP3 are destabilized by normal Tregs in heterozygous females compared with hemizygous males. Mutations in other domains affect chromatin opening differently, involving different cofactors and provoking more specific autoimmune pathology (dermatitis, colitis, diabetes), unmasked by immunological challenges or incrossing NOD autoimmune-susceptibility alleles. This work establishes that IPEX disease heterogeneity results from the actual mutations, combined with genetic and environmental perturbations, explaining then the intra-familial variation in IPEX.

Dispersing LiCl in Zwitterionic COF for Highly Efficient Ammonia Storage and Separation.

Efficient and inherently safe NH3 storage and separation are of significant importance for the chemical industry. Herein, we proposed zwitterionic COF as a porous host to disperse LiCl for highly efficient NH3 storage and separation with record adsorption capacity. The equivalently cationic and anionic groups in the channels of zwitterionic COF could act as two separated sites to facilitate the dispersion of LiCl, hence the optimal composite exhibits a high capture capacity of 44.98 mmol/g at 25 °C and 1 bar, far exceeding other existing porous materials. Notably, the adsorption capacity is completely reversible and the efficient separation of NH3 from NH3 /CO2 /N2 mixture is achieved through breakthrough experiments. DFT calculation combined with XPS and 7 Li NMR experimental results give insight into the interaction between zwitterionic COF and LiCl. This work extends possibilities for the development of efficient adsorbents for NH3 storage and separation.

Risk of cerebrovascular disease after cancer diagnosis in the United States.

The risk of subsequent cerebrovascular disease among cancer patients of multiple cancers in the US is not well understood. A total of 3,843,261 cancer patients diagnosed from 1975 to 2018, were included from the surveillance, epidemiology, and end results (SEER) database. Standardized mortality ratios (SMRs) and absolute excess risks (AERs) were estimated. The overall cerebrovascular disease SMR was 1.04 (95% CI, 1.03-1.04), and the AER per 10,000 person-years at risk was 0.89. When compared with the US general population, greater cerebrovascular disease risk was correlated with certain cancer sites, American Indian/Alaska Native race, Asian or Pacific Islander race, unmarried marital status, distant metastasis, younger age, and an earlier time of cancer diagnosis. Clinically, more precision and proactive strategies for cerebrovascular disease prevention are required to subgroup of cancer patients with a greater risk of cerebrovascular disease, especially within the first two months.

Two new species of the genus Homogryllacris (Orthoptera: Gryllacrididae) with the male of Homogryllacris irregularis Lu, Zhang & Bian, 2022 from Yunnan, China.

This paper reports two new species of the genus Homogryllacris Liu, 2007 from Yunnan, China. In addition, the male of Homogryllacris irregularis Lu, Zhang & Bian, 2022 is described for the first time.

Polypyrene Porous Organic Framework for Efficiently Capturing Electron Specialty Gases.

The polypyrene polymer with an extended π-conjugated skeleton is attractive for perfluorinated electron specialty gas (F-gas) capture as the high electronegativity of fluorine atoms makes F-gases strongly electronegative gases. Herein, a polypyrene porous organic framework (termed as Ppy-POF) with an extended π-conjugated structure and excellent acid resistance was constructed. Systematic studies have shown that the abundant π-conjugated structures and gradient electric field distribution in Ppy-POF can endow it exceptional adsorption selectivity for high polarizable F-gases and xenon (Xe), which has been collaboratively confirmed by single-component gas adsorption experiments, time-dependent adsorption rate tests, dynamic breakthrough experiments, etc. Electrostatic potential distribution and charge density difference based on Grand Canonical Monte Carlo simulations and density functional theory calculations demonstrate that the selective adsorption of F-gases and Xe in Ppy-POF is attributed to the strong charge-transfer effect and polarization effect between Ppy-POF and gases. These results manifest that the POF with an extended π-conjugated structure and gradient electric field distribution has great potential in efficiently capturing electron specialty gases.

Trace SO2 Gas Capture in Stable 3D Viologen Ionic Porous Organic Framework Microsphere.

Eliminating trace sulfur dioxide (SO2) using nanoporous adsorbents is industrially preferred yet of great challenge due to the competitive adsorption of CO2. Herein, we reported a highly stable 3D viologen porous organic framework (Viologen-POF) microsphere via one pot polymerization reaction of 4,4'-bipyridine and tetrakis(4-(bromomethyl)phenyl)methane. Compared to the previously reported irregular POF particles, viologen-POF microsphere shows better mass transfer uniformity. Owing to the intrinsic separated positive and negative electric charges center in viologen-POF microspheres, it exhibits excellent SO2 selective capture performance, which can be collaboratively confirmed by static single-component gas adsorption, time-dependent adsorption rate, and multicomponent dynamic breakthrough experiments. Viologen-POF exhibits high SO2 absorption capacity (1.45 mmol g-1) at ultralow pressure of 0.002 bar and high SO2/CO2 selectivity of 467 at 298 K and 100 kPa (SO2/CO2, 10/90, v/v). The theoretical calculations based on density functional theory (DFT) and DMol3 modules in Material Studio (MS) were also performed to elucidate the adsorption mechanism of viologen-POF toward SO2 at the molecular level. This study represents a new type of viologen porous framework microsphere for trace SO2 capture, which will pave the way on the applications of ionic POF for toxic gas adsorption and separation.

Homologous RuO2-Ru heterostructures for tandem catalytic upgrading of ethanol.

The homologous RuO2-Ru heterostructure was demonstrated as an efficient tandem catalyst for upgrading ethanol. The adjacent RuO2 and Ru separately serve as aldol condensation/dehydration and dehydrogenation/hydrogenation sites for ethanol conversion.

Robust Coarse Cage Construction with Small Approximation Errors.

We propose a robust and automatic method to construct manifold cages for 3D triangular meshes. The cage contains hundreds of triangles to tightly enclose the input mesh without self-intersections. To generate such cages, our algorithm consists of two phases: (1) construct manifold cages satisfying the tightness, enclosing, and intersection-free requirements and (2) reduce mesh complexities and approximation errors without violating the enclosing and intersection-free requirements. To theoretically make the first stage have those properties, we combine the conformal tetrahedral meshing and tetrahedral mesh subdivision. The second step is a constrained remeshing process using explicit checks to ensure that the enclosing and intersection-free constraints are always satisfied. Both phases use a hybrid coordinate representation, i.e., rational numbers and floating point numbers, combined with exact arithmetic and floating point filtering techniques to guarantee the robustness of geometric predicates with a favorable speed. We extensively test our method on a data set of over 8500 models, demonstrating robustness and performance. Compared to other state-of-the-art methods, our method possesses much stronger robustness.

iSnoDi-MDRF: Identifying snoRNA-Disease Associations Based on Multiple Biological Data by Ranking Framework.

Accumulating evidence indicates that the dysregulation of small nucleolar RNAs (snoRNAs) is relevant with diseases. Identifying snoRNA-disease associations by computational methods is desired for biologists, which can save considerable costs and time compared biological experiments. However, it still faces some challenges as followings: (i) Many snoRNAs are detected in recent years, but only a few snoRNAs have been proved to be associated with diseases; (ii) Computational predictors trained with only a few known snoRNA-disease associations fail to accurately identify the snoRNA-disease associations. In this study, we propose a ranking framework, called iSnoDi-MDRF, to identify potential snoRNA-disease associations based on multiple biological data, which has the following highlights: (i) iSnoDi-MDRF integrates ranking framework, which is not only able to identify potential associations between known snoRNAs and diseases, but also can identify diseases associated with new snoRNAs. (ii) Known gene-disease associations are employed to help train a mature model for predicting snoRNA-disease association. Experimental results illustrate that iSnoDi-MDRF is very suitable for identifying potential snoRNA-disease associations. The web server of iSnoDi-MDRF predictor is freely available at http://bliulab.net/iSnoDi-MDRF/.