Inorganic PM2.5 reduction in Kanto, Japan: The role of ammonia and its emission sources control strategies.

Ammonia (NH3) is attracting attention as a carbon-free energy source and a significant precursor to inorganic PM2.5 (hereafter PM2.5), aside from NOx and SOx. Since the emission of NH3 has often been overlooked compared to NOx and SOx, this study aims to reveal the role of NH3 and its emission control on PM2.5 in Kanto, Japan. With the aid of gas ratio (GR) quantitatively defining the stoichiometry between the three precursors to PM2.5, and the aid of atmospheric modeling software ADMER-PRO, coupled with thermodynamics calculations, the spatiotemporal distribution along with PM2.5 reduction under different NH3 emission cutoff strategies in Kanto had been revealed for the first time. The cutoff of NH3 emission could effectively reduce the PM2.5 concentration, with sources originated from agriculture, human/pet activities, and vehicle sources, overall giving a 93.32% PM2.5 reduction. Different cutoff strategies lead to distinct reduction efficiencies of the overall and local PM2.5 concentrations, with GR as a crucial factor. The regions with GR ∼1, are sensitive to the NH3 concentration for forming PM2.5, at which the NH3 reduction strategies should be applied with high priority. On the other hand, installing a new NH3 emission source should be avoided in the region with GR < 1, suppressing the so-yielded PM2.5 pollution. The future PM2.5 pollution control related to the NH3 emission control strategies based on GR, which is stoichiometry-based and applicable to regions other than Kanto, has been discussed.

Factors Affecting the Potential Efficacy of Intrauterine Platelet-Rich Plasma Infusion on Thin Endometrium in Women with Recurrent Implantation Failure.

Optimizing endometrial thickness (EMT) is crucial for successful embryo implantation, but enhancing thin endometrium remains a significant challenge. Platelet-rich plasma (PRP)-derived therapies have emerged as a promising approach in reproductive medicine due to their capacity to facilitate tissue repair and regeneration. This study aims to identify the risk factors associated with the failure of intrauterine PRP infusion for thin endometrium in women with recurrent implantation failure (RIF). We retrospectively reviewed data from 77 women with RIF, all exhibiting an EMT of <7 mm. These women underwent programmed hormone therapy for frozen embryo transfer (FET) and received two autologous intrauterine PRP infusions. Following intrauterine PRP-lysate (PL) infusions, the mean increase in EMT was 1.9 ± 1.2 mm, with EMT reaching 7 mm in 86% of the cases (66/77; average EMT, 8.3 mm). We identified an exceedingly thin EMT as a risk factor impacting the therapeutic efficacy in increasing EMT (p = 0.04, OR: 3.16; 95% CI: 1.03-9.67). Additionally, the number of previous uterine surgeries emerged as a prognostic factor for pregnancy failure following PL infusion (p = 0.02, OR: 2.02; 95% CI: 1.12-3.64). Our findings suggest that an extremely thin EMT and a history of numerous uterine surgeries can impede successful pregnancy, even when an optimal EMT is achieved following PRP infusion.

The presence of vacuoles in blastocysts is negatively associated with euploidy and live birth rates.

OBJECTIVE: To investigate whether the presence of vacuoles in biopsied blastocysts is associated with the likelihood of aneuploidy and clinical outcomes. DESIGN: Retrospective observational study. SETTING: A single reproductive center. INTERVENTION(S): None. PATIENT(S): This study retrospectively analyzed data obtained through preimplantation genetic testing for aneuploidy performed on 3351 blastocysts from 826 patients at a single reproductive center between August 2018 and July 2020. Ultimately, 167 single euploid blastocyst transfers were performed in these patients. Vacuoles existing in the trophectoderm or inner cell mass were observed using blastocyst biopsy. After the biopsy, all blastocysts were vitrified, and embryo transfer was performed in a subsequent treatment cycle. MAIN OUTCOME MEASURE(S): The associations between vacuoles and euploidy or live birth rates were assessed using logistic regression models and estimated adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULT(S): Of the 3351 blastocysts from 826 patients, 903 (26.9%) were discovered to have vacuoles. The vacuole-positive group had a significantly lower percentage of euploid blastocysts after TE biopsy than the vacuole-negative group (28.8% vs. 35.5%). Embryos with vacuoles were significantly more likely to be poor quality (30.6% vs. 18.2%). Logistic regression analyses revealed that euploid blastocysts were positively associated with the absence of vacuoles, maternal age, and good embryo quality (vacuole-negative group: adjusted OR 1.291; 95% CI: 1.089-1.530; age <38 years: adjusted OR 1.989; 95% CI: 1.692-2.337; good embryo quality: adjusted OR 1.703; 95% CI: 1.405-2.064). The implantation and live birth rates were significantly lower for the transferred single euploid blastocysts with vacuoles than those without (35.5% vs. 56.6%; 29.0% vs. 52.2%, respectively). The live birth rate was positively associated with the absence of vacuoles (adjusted OR 2.792; 95% CI: 1.180-6.608). CONCLUSION(S): The formation of vacuoles in blastocysts is associated with lower rates of euploidy and live birth. Blastocysts without vacuoles should thus be prioritized for embryo transfer in vitro fertilization cycles.

Design and Synthesis of Novel HIV-1 NNRTIs with Bicyclic Cores and with Improved Physicochemical Properties.

Non-nucleoside reverse transcriptase inhibitors (NNRTIs) represent cornerstones of current regimens for treatment of human immunodeficiency virus type 1 (HIV-1) infections. However, NNRTIs usually suffer from low aqueous solubility and the emergence of resistant viral strains. In the present work, novel bicyclic NNRTIs derived from etravirine (ETV) and rilpivirine (RPV), bearing modified purine, tetrahydropteridine, and pyrimidodiazepine cores, were designed and prepared. Compounds 2, 4, and 6 carrying the acrylonitrile moiety displayed single-digit nanomolar activities against the wild-type (WT) virus (EC50 = 2.5, 2.7, and 3.0 nM, respectively), where the low nanomolar activity was retained against HXB2 (EC50 = 2.2-2.8 nM) and the K103N and Y181C mutated strains (fold change, 1.2-6.7×). Most importantly, compound 2 exhibited significantly improved phosphate-buffered saline solubility (10.4 µM) compared to ETV and RPV (≪1 µM). Additionally, the binding modes of compounds 2, 4, and 6 to the reverse transcriptase were studied by X-ray crystallography.

Ammonia/ammonium removal/recovery from wastewaters using bioelectrochemical systems (BES): A review.

This review updates the current research efforts on using BES to recover NH3/NH4+, highlighting the novel configurations and introducing the working principles and the applications of microbial fuel cell (MFC), microbial electrolysis cell (MEC), microbial desalination cell (MDC), and microbial electrosynthesis cell (MESC) for NH3/NH4+ removal/recovery. However, commonly studied BES processes for NH3/NH4+ removal/recovery are energy intensive with external aeration needed for NH3 stripping being the largest energy input. In such a process bipolar membranes used for yielding a local alkaline pool recovering NH3 is not cost-effective. This gives a chance to microbial electrosynthesis which turned out to be a potential alternative option to approach circular bioeconomy. Furtherly, the reactor volume and NH3/NH4+ removal/recovery efficiency has a weakly positive correlation, indicating that there might be other factors controlling the reactor performance that are yet to be investigated.

A review on recovery of extracellular biopolymers from flocculent and granular activated sludges: Cognition, key influencing factors, applications, and challenges.

A reasonable recovery of excess sludge may shift the waste into wealth. Recently an increasing attention has been paid to the recycling of extracellular biopolymers from conventional and advanced biological wastewater treatment systems such as flocculent activated sludge (AS), bacterial aerobic granular sludge (AGS), and algal-bacterial AGS processes. This review provides the first overview of current research developments and future directions in the recovery and utilization of high value-added biopolymers from the three types of sludge. It details the discussion on the recent evolvement of cognition or updated knowledge on functional extracellular biopolymers, as well as a comprehensive summary of the operating conditions and wastewater parameters influencing the yield, quality, and functionality of alginate-like exopolymer (ALE). In addition, recent attempts for potential practical applications of extracellular biopolymers are discussed, suggesting research priorities for overcoming identification challenges and future prospects.

Nitrous oxide emission mitigation from biological wastewater treatment - A review.

Nitrous oxide (N2O) emitted from wastewater treatment processes has emerged as a focal point for academic and practical research amidst pressing environmental issues. This review presents an updated view on the biological pathways for N2O production and consumption in addition to the critical process factors affecting N2O emission. The current research trends including the strain and reactor aspects were then outlined with discussions. Last but not least, the research needs were proposed. The holistic life cycle assessment needs to be performed to evaluate the technical and economic feasibility of the proposed mitigation strategies or recovery options. This review also provides the background information for the proposed future research prospects on N2O mitigation and recovery technologies. As pointed out, dilution effects of the produced N2O gas product would hinder its use as renewable energy; instead, its use as an effective oxidizing agent is proposed as a promising recovery option.

Amorphous mesoporous matrix from metal-organic framework UiO-66 template with strong nucleophile substitution.

The metal-organic framework (MOF) UiO-66 is made of zirconium clusters coordinated with 1,4-benzenedicarboxylate linkers that is stable in water and is highly tolerant to extremely acidic or basic environments. Conversely, the zirconium clusters are affine to nucleophiles so the crystalline structures of UiO-66 can be converted into amorphous derivatives. In a mineral acid solution both protons and coordinating nucleophile are present. This study for the first time revealed that it is the strong nucleophile instead of proton deteriorate the crystalline structures of UiO-66. Also, the so-produced amorphous mesoporous matrix, if not totally dissolved, can be applied as an efficient adsorbent. The noted adsorption capabilities of Cu(II) and nucleophiles by these amorphous mesoporous matrix did not correlate with the structural crystallinity or the internal surface area; conversely, the doped nucleophiles were noted to contribute to the adsorption tendencies towards Cu(II) and phosphate species via electrostatic interactions and hydrogen bonding, respectively. Conversion of sacrificing UiO-66 template to amorphous matrix can be applied as an effective way to fabricate specific adsorbent with resistance to extreme pH and strong nucleophile challenges.

Long-wave infrared absorption measurement of undoped germanium using photothermal common-path interferometry.

Germanium is one of the most commonly used materials in the longwave infrared ($\lambda \sim{8 {-} 12}\;\unicode{x00B5}{\rm m}$λ∼8-12µm), but ironically, its absorption coefficient is poorly known in this range. An infrared photothermal common-path interferometry system with a tunable quantum cascade pump laser is used to measure the absorption coefficient of ${ \gt }{99.999}\% $>99.999% pure undoped germanium as a function of wavelengths between 9 and 11 µm, varying between about 0.15 and ${0.45}\;{{\rm cm}^{ - 1}}$0.45cm-1 over this range.

Alternative 3' splice site selection of intron 5 within the prmt8 gene results in a novel variant widely distributed in vertebrates and specifically abundant in Aves.

PRMT8 is a neuron-specific protein arginine methyltransferase in vertebrates. From data mining, we found a novel prmt8e6+43 splicing variant with a 43-nucleotide (nt) extension at the 5' of exon 6 in chicken. RT-PCR analyses confirmed the existence of two splicing variants but also detected a third upper signal. The triplet pattern detected in chicken suggests that one strand from the prmt8e6+43 transcript and one strand from the regular splicing products form a heteroduplex with a bulb conformation and the two transcripts are of similar abundance. One short plus one faint upper heteroduplex signal detected in mouse and human indicate that the level of the variant is much less than the normal one in mammals. The relative expression of the normal and prmt8e6+43 variants in different species can be inferred from the reads of intron 5 that contains the 43-nt extension or not in the RNA-seq data of NCBI Gene database. The results of the analyses showed that the prmt8e6+43 variant is relatively abundant in birds but much less or even not detected in mammalian species. As conserved intron 5 sequences and evidences of alternative splicing (AS) are detected in elephant shark, a cartilaginous fish with the slowest-evolving genome, we propose that the prmt8e6+43 variant is present in the common ancestor of jawed vertebrates. The prmt8e6+43 variant includes a premature termination codon and thus should encode a truncated PRMT8 with deletion from the dimerization arm. Western blot analyses showed very weak low-molecular-weight signals in chicken, which might be the C-terminal truncated PRMT8. Why avian species maintain high RNA but not protein levels of the prmt8e6+43 variant and whether the evolutionary conserved sequence and AS might regulate PRMT8 expression require further investigation.

High-Q diamond microresonators in the long-wave infrared.

High quality factor (Q) photonic devices in the room temperature thermal infrared region, corresponding to deeper long-wave infrared with wavelengths beyond 9 microns, have been demonstrated for the first time. Whispering gallery mode diamond microresonators were fabricated using single crystal diamond substrates and oxygen-based inductively coupled plasma (ICP) reactive ion etching (RIE) at high angles. The spectral characteristics of the devices were probed at room temperature using a tunable quantum cascade laser that was free space-coupled into the resonators. Light was extracted via an arsenic selenide (As2Se3) chalcogenide infrared fiber and directed to a cryogenically cooled mercury cadmium telluride (HgCdTe) detector. The quality factors were tested in multiple microresonators across a wide spectral range from 9 to 9.7 microns with similar performance. One example resonance (of many comparables) was found to reach 3648 at 9.601 µm. Fourier analysis of the many resonances of each device showed free spectral ranges slightly greater than 40 GHz, matching theoretical expectations for the microresonator diameter and the overlap of the whispering gallery mode with the diamond.

Impact of adding metal nanoparticles on anaerobic digestion performance - A review.

Anaerobic digestion is the most widely adopted biological waste treatment processes with renewable energy production. The effects of adding metal nanoparticles (NPs) on improving digestion performance are well noted. This paper reviewed the traditional view on the cytotoxicity of NPs to living organisms and the contemporary view of mechanisms for enhancement in anaerobic digestion performance in the presence of metal NPs. The complicated interactions acquire further studies for comprehending the physical and chemical interactions of metal NPs to the constituent compounds and to the living cells, and the involvement of mechanisms such as direct interspecies electron transfer for better design and control of the "NP strategy" for anaerobic digestion performance enhancement.

Discovery of velpatasvir (GS-5816): A potent pan-genotypic HCV NS5A inhibitor in the single-tablet regimens Vosevi® and Epclusa®.

Direct-acting antiviral inhibitors have revolutionized the treatment of hepatitis C virus (HCV) infected patients. Herein is described the discovery of velpatasvir (VEL, GS-5816), a potent pan-genotypic HCV NS5A inhibitor that is a component of the only approved pan-genotypic single-tablet regimens (STRs) for the cure of HCV infection. VEL combined with sofosbuvir (SOF) is Epclusa®, an STR with 98% cure-rates for genotype 1-6 HCV infected patients. Addition of the pan-genotypic HCV NS3/4A protease inhibitor voxilaprevir to SOF/VEL is the STR Vosevi®, which affords 97% cure-rates for genotype 1-6 HCV patients who have previously failed another treatment regimen.

Adsorption of hydrogen arsenate and dihydrogen arsenate ions from neutral water by UiO-66-NH2.

The metal-organic framework (MOF) UiO-66-NH2 was synthesized with different substrate to solvent ratios and its morphology, surface area, pore distributions, and NMR, XRD, and TGA-FTIR patterns were obtained. Adsorption tests at pH 7 and 25 °C showed that the produced UiO-66-NH2 has a hydrogen arsenate adsorption capacity of 76.9 mg/g. With the affinity onto Zr clusters, this MOF also can adsorb phosphate ions from water. Treatment with 1-4 M hydrochloric acid (HCl) protonated the amine groups in the MOF. Treatment with 1 M HCl at 25 °C for 6 h maximized the adsorption capacity of UiO-66-NH2 to 161.3 mg/g, such that the protonated amine groups accounted for 53.7% of the adsorption of arsenate from the water. The use of excessively strong acid at elevated temperature reduced the adsorption capacity.

Downregulation of PRMT1 promotes the senescence and migration of a non-MYCN amplified neuroblastoma SK-N-SH cells.

Protein arginine methyltransferase 1 (PRMT1) catalyzing the formation of asymmetric dimethylarginines has been implicated in cancer development, metastasis, and prognosis. In this study, we investigated the effects of low PRMT1 levels on a non-MYCN amplified neuroblastoma SK-N-SH cell line. Stable PRMT1-knockdown (PRMT1-KD) cells showed reduced growth rates and cell cycle arrest at G2/M. They also exhibited senescent phenotypes and increased p53 expression. p21 and PAI-1, which are two p53 downstream targets critical for senescence, were significantly induced in SK-N-SH cells subjected to either PRMT1-KD or inhibitor treatment. The induction was suppressed by a p53 inhibitor and marginal in a p53-null SK-N-AS cell line, suggesting dependence on p53. In general, the DNA damage and ROS levels of the PRMT1-KD SK-N-SH cells were slightly increased. Their migration activity also increased with the induction of PAI-1. Thus, PRMT1 downregulation released the repression of cellular senescence and migration activity in SK-N-SH cells. These results might partially explain the poor prognostic outcome of low PRMT1 in a non-MYCN-amplified cohort and indicate the multifaceted complexity of PRMT1 as a biological regulator of neuroblastoma.

Discovery of a Potent and Orally Bioavailable Cyclophilin Inhibitor Derived from the Sanglifehrin Macrocycle.

Cyclophilins are a family of peptidyl-prolyl isomerases that are implicated in a wide range of diseases including hepatitis C. Our aim was to discover through total synthesis an orally bioavailable, non-immunosuppressive cyclophilin (Cyp) inhibitor with potent anti-hepatitis C virus (HCV) activity that could serve as part of an all oral antiviral combination therapy. An initial lead 2 derived from the sanglifehrin A macrocycle was optimized using structure based design to produce a potent and orally bioavailable inhibitor 3. The macrocycle ring size was reduced by one atom, and an internal hydrogen bond drove improved permeability and drug-like properties. 3 demonstrates potent Cyp inhibition ( Kd = 5 nM), potent anti-HCV 2a activity (EC50 = 98 nM), and high oral bioavailability in rat (100%) and dog (55%). The synthetic accessibility and properties of 3 support its potential as an anti-HCV agent and for interrogating the role of Cyp inhibition in a variety of diseases.

Identification, chromosomal arrangements and expression analyses of the evolutionarily conserved prmt1 gene in chicken in comparison with its vertebrate paralogue prmt8.

Nine protein arginine methyltransferases (PRMTs) are conserved in mammals and fish. Among these, PRMT1 is the major type I PRMT for asymmetric dimethylarginine (ADMA) formation and is the most conserved and widely distributed one. Two chicken prmt1 splicing variants were assembled and confirmed by RT-PCR experiments. However, only two scaffolds containing single separate prmt1 exon with high GC contents are present in the current chicken genome assembly. Besides, prmt1 exons are scattered in separate small scaffolds in most avian species. Complete prmt1 gene has only been predicted from two falcon species with few neighboring genes. Crocodilians are considered close to the common ancestor shared by crocodilians and birds. The gene arrangements around prmt1 in American alligator are different from that in birds but are largely conserved in human. Orthologues of genes in a large segment of human chromosomal 19 around PRMT1 are missing or not assigned to the current chicken chromosomes. In comparison, prmt8, the prmt1 paralogue, is on chicken chromosome 1 with the gene arrangements downstream of prmt8 highly conserved in birds, crocodilians, and human. However, the ones upstream vary greatly in birds. Biochemically, we found that though prmt1 transcripts were detected, limited or none PRMT1 protein was present in chicken tissues. Moreover, a much higher level of PRMT8 protein was detected in chicken brain than in mouse brain. While PRMT8 is brain specific in other vertebrate species studied, low level of PRMT8 was present in chicken but not mouse liver and muscle. We also showed that the ADMA level in chicken was similar to that in mouse. This study provides the critical information of chicken PRMT1 and PRMT8 for future analyses of the function of protein arginine methyltransferases in birds.

Sludge treatment: Current research trends.

Sludge is produced during wastewater treatment as a residue containing most insoluble and adsorbed soluble impurities in wastewaters. This paper summarized the currently available review papers on sludge treatments and proposed the research trends based on the points raised therein. On partition aspect, sludge production rate and the reduction of production rate and the fate and transformation of involved emergent contaminants including endocrine disrupting chemicals and pharmaceuticals and personal care products are widely studied. On release aspect, development of thermal processes on sludge with migration and transformation of heavy metals in sludge during treatment is a research focus. The use of detailed fluid and biological reaction models and advanced instrumentation and control systems is studied to optimize treatment performances. On recovery part, co-digestion of sludge with co-substrates at mesophilic and hyperthermophilic conditions and the recovery of phosphorus at low costs are research highlights.

PRMT1 expression is elevated in head and neck cancer and inhibition of protein arginine methylation by adenosine dialdehyde or PRMT1 knockdown downregulates proliferation and migration of oral cancer cells.

Protein arginine methylation is a post-translational modification that has been implicated in signal transduction, gene transcription, DNA repair and RNA processing. Overexpression or deregulation of protein arginine methyltransferases (PRMTs) have been reported to be associated with various cancers but have not been studied in head and neck cancer (HNC). We investigated the involvement of the modification in HNC using oral cancer cell lines (SAS, OECM-1 and HSC-3) and an immortalized normal oral cells (S-G). The expression levels of the predominant PRMT1 were generally consistent with the levels of asymmetric dimethylarginine (ADMA), highest in SAS and OECM1, then S-G and low in HSC-3. Upon the treatment with an indirect methyltransferase inhibitor adenosine dialdehyde (AdOx), the ADMA levels in SAS and OECM1, but not that in S-G and HSC-3, decreased significantly. SAS and OECM with high ADMA levels grew faster than HSC-3 and S-G. The growth rate of the fast growing SAS and OECM, but not that of the other two cell lines, decreased significantly upon AdOx treatment. The migration activity of SAS and HSC-3, two cell lines with migration ability also decreased after the AdOx treatment. Immunohistochemical analyses of specimens from typical HNC patients showed strong PRMT1 expression in the tumor cells compared with neighboring normal cells. Knockdown of PRMT1 in SAS cells decreased the levels of PRMT1 and ADMA-containing proteins significantly. These cells showed decreased growth rate, reduced migration activity but increased expression of the epithelial marker E-cadherin. The present study thus provides fundamental background for evaluation of the PRMT1 gene as the therapeutic targets of HNC.

Photo-fermentative hydrogen production in a 4m3 baffled reactor: Effects of hydraulic retention time.

A 4m3 pilot-scale baffled continuous-flow photoreactor with four sequential chambers (#1-#4) was established and tested to evaluate its photo-fermentative hydrogen production from wastewater that contains (10g/L glucose using a functional consortium at 30°C, under light with an intensity of 3000±200lux with a hydraulic retention time (HRT) of 24-72h. The hydrogen production rate and the broth characteristics varied significantly in the flow direction. The hydrogen production rate was highest in chamber #1, and lower in chambers #2-#4 at an HRT of 72h, while the peak production rate shifted to the latter chambers as the HRT was shortened. The overall H2 production rate increased as HRT decreased, but was not consistent with the predictions that were based on the complete-mixing assumption.