Thermodynamic H-Abstraction Abilities of Nitrogen Centered Radical Cations as Potential Hydrogen Atom Transfer Catalysts in Y-H Bond Functionalization.

Y-H bond functionalization has always been the focus of research interest in the area of organic synthesis. Direct hydrogen atom transfer (HAT) from the Y-H bond is one of the most efficient and practical methods to activate the Y-H bond. Recently, nitrogen centered radical cations were broadly utilized as H-abstraction catalysts to activate Y-H bonds via the HAT process. As a type of HAT catalyst, the H-affinity of nitrogen centered radical cations is a significant thermodynamic parameter to quantitatively evaluate the thermodynamic H-abstraction potentials of nitrogen centered radical cations. In this work, the pK a values of 120 protonated N-containing compounds in acetonitrile (AN) are predicted, and the H-affinities of 120 nitrogen centered radical cations in AN are derived from the reduction potentials of nitrogen centered radical cations and pK a of protonated N-containing compounds using Hess' law. This work focuses on the H-abstraction abilities of 120 nitrogen centered radical cations in AN to enrich the molecule library of novel HAT catalysts or H-abstractors and provides valuable thermodynamic guidelines for the application of nitrogen centered radical cations in Y-H bond functionalization.

Identification of subgroups and development of prognostic risk models along the glycolysis-cholesterol synthesis axis in lung adenocarcinoma.

Lung cancer is one of the most dangerous malignant tumors affecting human health. Lung adenocarcinoma (LUAD) is the most common subtype of lung cancer. Both glycolytic and cholesterogenic pathways play critical roles in metabolic adaptation to cancer. A dataset of 585 LUAD samples was downloaded from The Cancer Genome Atlas database. We obtained co-expressed glycolysis and cholesterogenesis genes by selecting and clustering genes from Molecular Signatures Database v7.5. We compared the prognosis of different subtypes and identified differentially expressed genes between subtypes. Predictive outcome events were modeled using machine learning, and the top 9 most important prognostic genes were selected by Shapley additive explanation analysis. A risk score model was built based on multivariate Cox analysis. LUAD patients were categorized into four metabolic subgroups: cholesterogenic, glycolytic, quiescent, and mixed. The worst prognosis was the mixed subtype. The prognostic model had great predictive performance in the test set. Patients with LUAD were effectively typed by glycolytic and cholesterogenic genes and were identified as having the worst prognosis in the glycolytic and cholesterogenic enriched gene groups. The prognostic model can provide an essential basis for clinicians to predict clinical outcomes for patients. The model was robust on the training and test datasets and had a great predictive performance.

Evaluation of Organic Hydride/Acid Pairs as a Type of Thermodynamic-Potential-Regulated Multisite Proton-Coupled Electron Transfer Reagents.

Organic hydride/acid pairs have been reported as multisite proton-coupled electron transfer (MS-PCET) reagents in reductive MS-PCET reactions recently. Since the key step for an organic hydride/acid pair acting as an MS-PCET reagent is a chemical process of the organic hydride/acid pair releasing a formal hydrogen atom, the bond dissociation free energy of the organic hydride/acid pair releasing a formal hydrogen atom is a valuable thermodynamic parameter for objectively evaluating the thermodynamic potential for an organic hydride/acid pair to act as an MS-PCET reagent. Now, organic hydride/acid pairs of 216 organic hydrides have been demonstrated to be a potential type of thermodynamically potential-regulated MS-PCET reagent. Without a doubt, organic hydride/acid pairs reflect the change of N-substituted organic hydrides from simple hydride reductants to thermodynamically-regulated MS-PCET reagents, which could significantly expand the availability of novel MS-PCET reagents.

Clinical efficacy and mechanism study of mid-frequency anti-snoring device in treating moderate obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is primarily caused by airway obstruction due to narrowing and blockage in the nasal and nasopharyngeal, oropharyngeal, soft palate, and tongue base areas. The mid-frequency anti-snoring device is a new technology based on sublingual nerve stimulation. Its principle is to improve the degree of oropharyngeal airway stenosis in OSAHS patients under mid-frequency wave stimulation. Nevertheless, there is a lack of clinical application and imaging evidence. AIM: To investigate the clinical efficacy and mechanisms of a mid-frequency anti-snoring device in treating moderate OSAHS. METHODS: We selected 50 patients diagnosed with moderate OSAHS in our hospital between July 2022 and August 2023. They underwent a 4-wk treatment regimen involving the mid-frequency anti-snoring device during nighttime sleep. Following the treatment, we monitored and assessed the sleep apnea quality of life index and Epworth Sleepiness Scale scores. Additionally, we performed computed tomography scans of the oropharynx in the awake state, during snoring, and while using the mid-frequency anti-snoring device. Cross-sectional area measurements in different states were taken at the narrowest airway point in the soft palate posterior and retrolingual areas. RESULTS: Compared to pretreatment measurements, patients exhibited a significant reduction in the apnea-hypopnea index, the percentage of time with oxygen saturation below 90%, snoring frequency, and the duration of the most prolonged apnea event. The lowest oxygen saturation showed a notable increase, and both sleep apnea quality of life index and Epworth Sleepiness Scale scores improved. Oropharyngeal computed tomography scans revealed that in OSAHS patients cross-sectional areas of the oropharyngeal airway in the soft palate posterior area and retrolingual area decreased during snoring compared to the awake state. Conversely, during mid-frequency anti-snoring device treatment, these areas increased compared to snoring. CONCLUSION: The mid-frequency anti-snoring device demonstrates the potential to enhance various sleep parameters in patients with moderate OSAHS, thereby improving their quality of life and reducing daytime sleepiness. These therapeutic effects are attributed to the device's ability to ameliorate the narrowing of the oropharynx in OSAHS patients.

High arsenic pollution of the eutrophic Lake Taihu and its relationship with iron, manganese, and dissolved organic matter: High-resolution synchronous analysis.

Arsenic (As) is a metalloid that can accumulate in eutrophic lakes and cause adverse health effects to people worldwide. However, the seasonal process and dynamic mechanism for As mobilization in eutrophic lake remains effectively unknown. Here we innovatively used the planar optodes (PO), high-resolution dialysis (HR-Peeper) combined with fluorescence excitation-emission matrix coupled with parallel factor (EEM-PARAFAC) analysis technologies. We synchronously investigate monthly O2, As, iron (Fe), manganese (Mn), and naturally occurring dissolved organic matter (DOM) changes in sediments of Lake Taihu at high resolution in field conditions. We find high As contamination from sediments with 61.88-327.07 µg m-2 d-1 release As fluxes during the algal bloom seasons from May to October 2021. Our results show that an increase in DOM, mainly for humic-like components, resulting in high electron transfer capacity (ETC), promoted the reductive dissolution of Fe and Mn oxides to release As. Partial least square-path modeling (PLS-PM) and random forest modeling analysis identified that Mn oxide reductive dissolution directly accelerated sediments As contamination, which is the crucial factor. Understanding crucial factor controlling As release is especially essential in areas of eutrophic lakes developing effective strategies to manage As-rich eutrophic lake sediments worldwide.

Geochemical characteristics and environmental implication of rare earth elements in sediments from the Three Gorges Reservoir, China.

The construction and operation of the Three Gorges Dam occluded sediment transportation in the Yangtze River. However, the sources, transport processes, and environmental impacts of these sediments on the Three Gorges Reservoir (TGR) remain unclear. Here, we used rare earth elements (REEs) to trace the transport pathways of sediments in the TGR, China. Geochemical characteristics including the chemical composition and fractionation, temporal and spatial distribution, and potential sources of REEs were also evaluated in this study. The individual REEs concentration in the TGR sediments followed the Oddo-Harkins rule, with the mean REEs value of 207.33 µg/g. REEs concentrations in the midstream were higher than those in the upstream and downstream of the TGR. Statistical analysis showed that water impoundment phase had no significant influence on the distribution of REEs. TGR sediments are mainly derived from terrigenous detrital particulates, characterized by a distinctive enrichment in light REEs, with its percentage higher than 90 % of the total REEs. The significant positive correlation among the REEs confirmed that they are co-existed and shared the similar sources. Multiple provenance analysis approaches using discriminant function analyses, provenance indices, and La/Yb-La/Sm-Gd/Yb ternary diagrams further indicated that the REEs in sediments originated from the weathering of mudstone in the basin of TGR. After periodic water level fluctuation for more than six years, the chemical compositions of REEs in TGR sediments slightly differed from those of the Yangtze River sediments before TGR construction, but were similar to those of the downstream of the Yangtze River. Therefore, this study indicated that the construction and operation of the TGR changed the chemical compositions and the origin of the sediments in the Yangtze River, which can provide useful insights into the transport pathways of TGR sediments and their impacts on the fluvial environment.

Thermodynamic evaluations of the acceptorless dehydrogenation and hydrogenation of pre-aromatic and aromatic N-heterocycles in acetonitrile.

N-heterocycles are important chemical hydrogen-storage materials, and the acceptorless dehydrogenation and hydrogenation of N-heterocycles as organic hydrogen carriers have been widely studied, with the main focus on the catalyst synthesis and design, investigation of the redox mechanisms, and extension of substrate scope. In this work, the Gibbs free energies of the dehydrogenation of pre-aromatic N-heterocycles (YH2) and the hydrogenation of aromatic N-heterocycles (Y), i.e., ΔGH2R(YH2) and ΔGH2A(Y), were derived by constructing thermodynamic cycles using Hess' law. The thermodynamic abilities for the acceptorless dehydrogenation and hydrogenation of 78 pre-aromatic N-heterocycles (YH2) and related 78 aromatic N-heterocycles (Y) were well evaluated and discussed in acetonitrile. Moreover, the applications of the two thermodynamic parameters in identifying pre-aromatic N-heterocycles possessing reversible dehydrogenation and hydrogenation properties and the selection of the pre-aromatic N-heterocyclic hydrogen reductants in catalytic hydrogenation were considered and are discussed in detail. Undoubtedly, this work focuses on two new thermodynamic parameters of pre-aromatic and aromatic N-heterocycles, namely ΔGH2R(YH2) and ΔGH2A(Y), which are important supplements to our previous work to offer precise insights into the chemical hydrogen storage and hydrogenation reactions of pre-aromatic and aromatic N-heterocycles.

Characterization of the CMS genetic regulation through comparative complete mitochondrial genome sequencing in Nicotiana tabacum.

Mitochondrial genomes (mitogenomes) of flowering plants vary greatly in structure and size, which can lead to frequent gene mutation, rearrangement, or recombination, then result in the cytoplasmic male sterile (CMS) mutants. In tobacco (Nicotiana tabacum), suaCMS lines are widely used in heterosis breeding; however, the related genetic regulations are not very clear. In this study, the cytological observation indicated that the pollen abortion of tobacco suaCMS(HD) occurred at the very early stage of the stamen primordia differentiation. In this study, the complete mitochondrial genomes of suaCMS(HD) and its maintainer HD were sequenced using the PacBio and Illumina Hiseq technology. The total length of the assembled mitogenomes of suaCMS(HD) and HD was 494,317 bp and 430,694 bp, respectively. Comparative analysis indicated that the expanded 64 K bases in suaCMS(HD) were mainly located in noncoding regions, and 23 and 21 big syntenic blocks (>5000 bp) were found in suaCMS(HD) and HD with a series of repeats. Electron transport chain-related genes were highly conserved in two mitogenomes, except five genes (ATP4, ATP6, COX2, CcmFC, and SDH3) with substantial substitutions. Three suaCMS(HD)-specific genes, orf261, orf291, and orf433, were screened. Sequence analysis and RT-PCR verification showed that they were unique to suaCMS(HD). Further gene location analysis and protein property prediction indicated that all the three genes were likely candidates for suaCMS(HD). This study provides new insight into understanding the suaCMS mechanism and is useful for improving tobacco breeding.

Thermodynamic Evaluations of Amines as Hydrides or Two Hydrogen Ions Reductants and Imines as Protons or Two Hydrogen Ions Acceptors, as Well as Their Application in Hydrogenation Reactions.

Since the hydrogenation of imines (X) and the dehydrogenation of amines (XH2) generally involve the two hydrogen ions (H- + H+) transfer, the thermodynamic abilities of various amines releasing hydrides or two hydrogen ions as well as various imines accepting protons or two hydrogen ions are important and characteristic physical parameters. In this work, the pKa values of 84 protonated imines (XH+) in acetonitrile were predicted. Combining Gibbs free energy changes of amines releasing hydrides in acetonitrile from our previous work with the pKa(XH+) values, the Gibbs free energy changes of amines releasing two hydrogen ions and imines accepting two hydrogen ions were derived using Hess's law by constructing thermochemical cycles, and the thermodynamic evaluations of amines as hydrides or two hydrogen ions reductants and imines as protons or two hydrogen ions acceptors are well compared and discussed. Eventually, the practical application of thermodynamic data for amines and imines on hydrogenation feasibility, mechanism, and possible elementary steps was shown and discussed in this paper from the point of thermodynamics.

Quantitative 1H NMR with global spectral deconvolution approach for quality assessment of natural and cultured Cordyceps sinensis.

Cordyceps sinensis is a precious medicinal food which has been successfully cultivated indoors. It remains to be investigated for a simultaneous comparison on aqueous components of natural and cultivated samples. Herein, an approach of quantitative nuclear magnetic resonance (qNMR) analysis combined with global spectral deconvolution (GSD) was established for simultaneous quantification of 26 aqueous components in C. sinensis. Processed by GSD, the distorted baselines of 1H NMR spectra were greatly improved, and overlapped signals were also well separated so as to achieve accurate identification and quantitation of components in C. sinensis. Method validation by UHPLC-QTOF-MS and TOF-SIMS analysis revealed that qNMR combined with GSD is a reliable approach for simultaneous quantification of multiple components including characteristic markers of glutamine, GABA and trehalose in authentic and fake C. sinensis. The well-established qNMR approach can be used for quality assessment of natural and cultivated C. sinensis as well as differentiation from fake ones.

The Application of Sulfonyl Hydrazides in Electrosynthesis: A Review of Recent Studies.

Sulfonyl hydrazides are viewed as alternatives to sulfinic acids and their salts or sulfonyl halides, which are broadly used in organic synthesis or work as active pharmaceutical substances. Generally, sulfonyl hydrazides are considered good building blocks and show powerful value in a diverse range of reactions to construct C-S bonds or C-C bonds, and even C-N bonds as sulfur, carbon, or nitrogen sources, respectively. As a profound synthetic tool, the electrosynthesis method was recently used to achieve efficient and green applications of sulfonyl hydrazides. Interestingly, many unique and novel electrochemical syntheses using sulfonyl hydrazides as radical precursors have been developed, including cascade reactions, functionalization of heterocycles, as well as a continuous flow method combining with electrochemical synthesis since 2017. Accordingly, it is necessary to specifically summarize the recent developments of electrosynthesis with only sulfonyl hydrazides as radical precursors to more deeply understand and better design novel electrochemical synthesis reactions. Herein, electrosynthesis research using sulfonyl hydrazides as radical precursors since 2017 is reviewed in detail based on the chemical structures of products and reaction mechanisms.

Influence of dietary protein on serum phosphorous levels in peritoneal dialysis patients with different initial transport function.

INTRODUCTION: This cross-sectional study investigated the influence of dietary protein intake (DPI) on serum phosphate levels in peritoneal dialysis (PD) patients and determined the DPI cutoff required to prevent hyperphosphatemia. METHODS: A total of 504 PD patients were categorized into fast (4 h dialysate/plasma [D/P] creatinine clearance ≥0.65) or slow (<0.65) peritoneal transporters. Serum phosphorus and peritoneal solute clearance were compared between the groups with different DPI. RESULTS: The fast peritoneal transporters (n = 233) were older, had lower serum albumin and phosphorus levels, and had higher peritoneal phosphorus clearance (all p < 0.001). Among the slow transporters (n = 271), serum phosphorus levels were significantly higher among patients with DPI > 1.0 g/kg/d (p < 0.001). High DPI only increased the hyperphosphatemia risk in slow transporters (not in high transporters). DPI ≥1.026 g increased the hyperphosphatemia risk in those patients (area under the curve: 0.66, p = 0.001). CONCLUSION: High DPI increases the hyperphosphatemia risk in PD patients with slower peritoneal transport function.

Theoretical Study for Evaluating and Discovering Organic Hydride Compounds as Potential Novel Methylation Reagents.

Methylation reaction is a fundamental chemical reaction that plays an important role in the modification of drug molecules, DNA, as well as proteins. This work focuses on seeking potential novel methylation reagents through a systematic investigation of the thermodynamics and reactivity of methyl-substituted organic hydride radical cations (XH•+s). In this work, 45 classical and important XH•+s were designed to investigate the relationship between their structure and reactivity, to find excellent or potential methylation reagents. The Gibbs free energy and activation free energy of XH•+ to release the methyl radical in MeCN at 298.15 and 355 K are calculated with the density functional theory (DFT) method to quantitatively measure the reactivity of XH•+ as a methylation reagent in this work. The relationships between structures and reactivities on XH•+s as methylation reagents are well examined. Since we have calculated the Gibbs free energy and activation free energy of trifluoromethyl-substituted organic hydride compound radical cations (X'H•+) releasing trifluoromethyl radicals in MeCN with the DFT method in our previous work, accordingly, the relationship of thermodynamics and reactivity between X'H•+ releasing trifluoromethyl radical and XH•+ releasing methyl radical is discussed in detail. Excitingly, 4 XH•+s (1H•+, 3H•+∼4H•+, and 44H•+) are found to be excellent methyl radical reagents, while 9 XH•+s (5H•+, 6H•+, 9H•+, 10H•+, 12H•+, 13H•+, 15H•+, 43H•+, and 45H•+) are found to be potential methyl radical reagents in chemical synthesis. The molecular library and reactivity database of novel methylation reagents could be established for synthetic chemists to query and use. Our work may offer a theoretical basis and reference experience for screening different substituted organic hydride compounds (YRHs) as alkylation reagents.

Isolated gastric variceal bleeding related to non-cirrhotic portal hypertension following oxaliplatin-based chemotherapy: A case report.

BACKGROUND: Sinusoidal obstruction syndrome has been reported after oxaliplatin-based chemotherapy, but liver fibrosis and non-cirrhotic portal hypertension (NCPH) are rarely reported. CASE SUMMARY: Here, we describe the case of a 64-year-old woman who developed isolated gastric variceal bleeding 16 mo after completing eight cycles of oxaliplatin combined with capecitabine chemotherapy after colon cancer resection. Surprisingly, splenomegaly and thrombocytopenia were not accompanied by variceal bleeding, which has been reported to have predictive value for gastric variceal formation. However, a liver biopsy showed fibrosis in the portal area, suggesting NCPH. The patient underwent endoscopic treatment and experienced no further symptoms. CONCLUSION: It is necessary to guard against long-term complications after oxaliplatin-based chemotherapy. Sometimes splenic size and platelet level may not always accurately predict the occurrence of portal hypertension.

Discovering and Evaluating the Reducing Abilities of Polar Alkanes and Related Family Members as Organic Reductants Using Thermodynamics.

In this work, the pKa values of 69 polar alkanes (YH2) in acetonitrile were computed using the method developed by Luo and Zhang in 2020, and representative 69 thermodynamic network cards on 22 elementary steps of YH2 and related polar alkenes (Y) releasing or accepting H2 were naturally established. Potential electron reductants (YH-), hydride reductants (YH-), antioxidants (YH2 and YH-), and hydrogen molecule reductants (YH2) are unexpectedly discovered according to thermodynamic network cards. It is also found that there are great differences between YH2 and common hydrogen molecule reductants (XH2), such as Hantzsch ester (HEH2), benzothiazoline (BTH2), and dihydro-phenanthridine (PH2), releasing two hydrogen ions to unsaturated compounds. During the hydrogenation process, XH2 release hydrides first, then the oxidation state XH+ release protons. However, in the case of YH2, YH2 release protons first, then YH- release hydrides. It is the differences on acidic properties of YH2 and XH2 that result in the behavioral and thermodynamic differences on YH2 and XH2 releasing two hydrogen ions (H--H+). The redox mechanisms and behaviors of Y, YH-, and YH2 as electron, hydrogen atom, hydride, and hydrogen molecule donors or acceptors in the chemical reaction are reasonably investigated and discussed in this paper using thermodynamics.

In situ Chemical Profiling and Imaging of Cultured and Natural Cordyceps sinensis by TOF-SIMS.

Time-of-flight secondary ion mass spectrometry (TOF-SIMS) is a sensitive surface analytical technology, which can simultaneously acquire diverse chemical components and their precise locations on the surfaces of samples without any requirements for chemical damage pretreatments or additional matrices. Commonly, the quality control of TCMs (traditional Chinese medicines) is limited by the qualitative and quantitative evaluations of the specifically extractive constituents. In this study, a practical sample preparation strategy named two-layered media embedding sample preparation was developed to obtain ideal freezing sections of dried materials of Cordyceps sinensis. Meanwhile, the well-established sample preparation method was applied for in situ chemical profiling and imaging of natural (NCS) and cultured Cordyceps sinensis (CCS) by using TOF-SIMS. More than 200 components were tentatively identified and imaged in NCS and CCS at the same time. Mass spectrometry imaging revealed that most components have even distributions in caterpillars of Cordyceps sinensis, while TAGs, DAGs, MAGs, and FAs only have distributions outside caterpillars' digestive chambers. This is the first time that components were in situ imaged for Cordyceps sinensis to exhibit the chemical distributions which have never been achieved by other analytical techniques so far. In addition, chemometrics was used to simplify and explain the massive TOF-SIMS mass data sets, which revealed the high chemical similarity between CCS and NCS. Furthermore, the relative quantification of TOF-SIMS data showed that CCS has comparable proportions of amino acids, nucleosides, monosaccharides, sphingolipids, sterols and other principles to NCS except for fatty acids, glycerides and glycerophospholipids. The higher amounts of TAGs and DAGs in CCS were confirmed by quantitative 1H-NMR, indicating reliable relative quantification of TOF-SIMS. In general, our research developed a novel approach of TOF-SIMS for in situ chemical analysis of TCMs, and its successful application in comparative study of CCS and NCS suggested that TOF-SIMS is an advanced and promising analytical technology for the research of TCMs.

Comparative Efficacy of Pharmacological Therapies for Low Back Pain: A Bayesian Network Analysis.

Low back pain (LBP) is a common problem, but the efficacy of pharmacological therapies remains controversial. Therefore, we aimed to comprehensively evaluate and quantitatively rank various pharmacological therapies for patients with low back pain. Two meta-analyses were performed: an initial pair-wise meta-analysis, followed by network meta-analysis using a random-effects Bayesian model. We included randomized controlled trials comparing placebos, non-steroidal anti-inflammatory drugs, opioids, skeletal muscular relaxants, pregabalin (or gabapentin), and some drug combinations. The primary and secondary outcomes were pain intensity and physical function. Eighty-eight eligible trials with 21,377 patients were included. Here, we show that only skeletal muscle relaxants significantly decreased the pain intensity of acute (including subacute) low back pain. Several kinds of drugs significantly decreased the pain of chronic low back pain, but only opioids and cyclo-oxygenase 2-selective non-steroidal anti-inflammatory drugs effectively reduced pain and improved function. Pregabalin (or gabapentin) seemed to be an effective treatment to relieve pain, but it should be used with caution for low back pain.