Photoinduced Pd-Catalyzed Enantioselective Carboamination of Dienes via Aliphatic C-H Bond Elaboration.

Three-component diene carboaminations offer a potent means to access synthetically valuable allylic amines with rapid molecular complexity escalation. The existing literature primarily discloses racemic examples, necessitating the use of halides/pseudohalides as substrates. This paper introduces a photoinduced Pd-catalyzed enantioselective three-component carboamination of aryl-substituted 1,3-dienes, leveraging aliphatic C-H bonds for rapid synthesis. The reaction employs 10 mol % of chiral palladium catalyst and an excess aryl bromide as the HAT reagent. This approach yields diverse chiral allylamines with moderate to excellent enantioselectivities. Notably, it stands as the first instance of an asymmetric three-component diene carboamination reaction, directly utilizing abundant C(sp3)-H bearing partners, such as toluene-type substrates, ethers, amines, esters, and ketones. The protocol exhibits versatility across amines, encompassing aliphatic, aromatic, primary, and secondary derivatives. This method could serve as a versatile platform for stereoselective incorporation of various nucleophiles, dienes, and C(sp3)-H bearing partners.

Severity-stratification of interstitial lung disease by deep learning enabled assessment and quantification of lesion indicators from HRCT images.

BACKGROUND: Interstitial lung disease (ILD) represents a group of chronic heterogeneous diseases, and current clinical practice in assessment of ILD severity and progression mainly rely on the radiologist-based visual screening, which greatly restricts the accuracy of disease assessment due to the high inter- and intra-subjective observer variability. OBJECTIVE: To solve these problems, in this work, we propose a deep learning driven framework that can assess and quantify lesion indicators and outcome the prediction of severity of ILD. METHODS: In detail, we first present a convolutional neural network that can segment and quantify five types of lesions including HC, RO, GGO, CONS, and EMPH from HRCT of ILD patients, and then we conduct quantitative analysis to select the features related to ILD based on the segmented lesions and clinical data. Finally, a multivariate prediction model based on nomogram to predict the severity of ILD is established by combining multiple typical lesions. RESULTS: Experimental results showed that three lesions of HC, RO, and GGO could accurately predict ILD staging independently or combined with other HRCT features. Based on the HRCT, the used multivariate model can achieve the highest AUC value of 0.755 for HC, and the lowest AUC value of 0.701 for RO in stage I, and obtain the highest AUC value of 0.803 for HC, and the lowest AUC value of 0.733 for RO in stage II. Additionally, our ILD scoring model could achieve an average accuracy of 0.812 (0.736 - 0.888) in predicting the severity of ILD via cross-validation. CONCLUSIONS: In summary, our proposed method provides effective segmentation of ILD lesions by a comprehensive deep-learning approach and confirms its potential effectiveness in improving diagnostic accuracy for clinicians.

Chiral Bisphosphoric Acids and Their Applications in Asymmetric Catalysis.

Asymmetric Brønsted acid catalysis has been recognized as a powerful concept for asymmetric synthesis. In the process of pursuing more robust and highly effective chiral Brønsted acid catalysts, chiral bisphosphoric acids have received much attention in the last two decades. Their unique catalytic properties are mainly attributed to the inherent intramolecular hydrogen bonding interactions that could increase the overall acidity and tune the conformation property. Integrating hydrogen bonding into the catalyst design, quite a few structurally unique and effective bisphosphoric acids have been synthesized, which frequently exhibited superior selectivity in a broad range of asymmetric transformations. This review summarizes the status quo of chiral bisphosphoric acid catalysts and their applications in catalyzing asymmetric transformations.

Asymmetric Cascade Carbonylation/Annulation of Benzyl Bromides, CO, and Vinyl Benzoxazinanones Enabled by Pd/Chiral Lewis-Base Relay Catalysis.

A highly enantioselective cascade carbonylation/annulation of benzyl bromides, CO, and vinyl benzoxazinanones under mild conditions has been established by Pd/chiral Lewis base relay catalysis, providing an efficient method to assemble chiral quinolinones from readily available starting materials in good yields with excellent diastereo- and enantioselectivities. The palladium catalyst plays two roles in this reaction, enabling both the carbonylation process and the generation of the zwitterionic π-allyl palladium intermediate.

Asymmetric construction of phosphono dihydropyranones from α-ketophosphonates enabled by Pd/chiral isothiourea relay catalysis.

A highly enantio- and diastereoselective approach has been developed for the synthesis of chiral phosphono dihydropyranones. This approach is enabled by Pd/chiral isothiourea relay catalysis under mild reaction conditions, starting from readily available benzyl bromides, CO, and α-ketophosphonates. The cascade reaction involves the generation of a ketene intermediate from Pd-catalyzed carbonylation of benzyl bromide and subsequent chiral Lewis base catalyzed formal [4 + 2] reaction. Phosphono lactone products can also be transformed to chiral 1,5-diester products in good yield and high stereoselectivity.

Environmental, economic, and energy analysis of municipal solid waste incineration under anoxic environment in Tibet Plateau.

The first Municipal solid waste incineration (MSWI) plant in Lhasa, Tibet, the plateau region of China, started its operation in 2018. Considering the elevation and extreme climate (low pressure and low oxygen content) in Tibet, noticeable differences may be envisaged compared to MSWI elsewhere. The aim of this study is to evaluate the environmental impacts, economic benefits, and energy efficiency of this MSWI project with three representative MSWI case in plain region using Life cycle assessment (LCA), Cost-benefit analysis (CBA), and energy analysis methods. The result showed that enhancing blast volume and cross-sectional area of the boiler help adapt to the oxygen-deficient environment. GaBi model was employed based on the CML 2001 methodology to perform LCA. LCA shows that the Lhasa MSWI project has lower positive environment impacts than the projects in plain region. More attention is needed for the deficiencies in flue gas emissions of MSWI in the plateau region. CBA shows that the payback period is 11.97 years and the internal rate of return is 8.75%. The energy analysis indicates that the boiler energy efficiency is up to 81.92%. MSWI subject to minor changes seems suitable to Tibetan plateau, and can be deployed further.

An explorative assessment of ChatGPT as an aid in medical education: Use it with caution.

OBJECTIVE: To explore the use of ChatGPT by educators and students in a medical school setting. METHOD: This study used the public version of ChatGPT launched by OpenAI on November 30, 2022 (https://openai.com/blog/chatgpt/). We employed prompts to ask ChatGPT to 1) generate a content outline for a session on the topics of cholesterol, lipoproteins, and hyperlipidemia for medical students; 2) produce a list of learning objectives for the session; and 3) write assessment questions with and without clinical vignettes related to the identified learning objectives. We assessed the responses by ChatGPT for accuracy and reliability to determine the potential of the chatbot as an aid to educators and as a "know-it-all" medical information provider for students. RESULTS: ChatGPT can function as an aid to educators, but it is not yet suitable as a reliable information resource for educators and medical students. CONCLUSION: ChatGPT can be a useful tool to assist medical educators in drafting course and session content outlines and create assessment questions. At the same time, caution must be taken as ChatGPT is prone to providing incorrect information; expert oversight and caution are necessary to ensure the information generated is accurate and beneficial to students. Therefore, it is premature for medical students to use the current version of ChatGPT as a "know-it-all" information provider. In the future, medical educators should work with programming experts to explore and grow the full potential of AI in medical education.

Palladium-Catalyzed Cascade C-H Functionalization/Asymmetric Allylation Reaction of Aryl α-Diazoamides and Allenes: Lewis Acid Makes a Difference.

A Pd-catalyzed cascade C-H functionalization/asymmetric allylation reaction with aryl α-diazoamides and allenes has been developed. The reaction provides an efficient approach to construct chiral 3,3-disubstituted oxindole derivatives in high levels of yield and enantioselectivity (up to 93 % ee). Notably, the chromium complex works as Lewis acid to facilitate the formation of palladium carbene and to enhance acidity of carboxylic acid, allowing for higher stereochemical control and efficiency.

Racial/ethnic disparities on inflammation and response to methylprednisolone in severe COVID-19 pneumonia.

BACKGROUND: Racial/ethnic minorities are at higher risk for severe COVID-19. This may be related to social determinants that lead to chronic inflammatory states. The aims of the study were to determine if there are racial/ethnic disparities with inflammatory markers and association of methylprednisolone to in hospital survival. METHODS: This was a secondary analysis of a retrospective cohort study of patients ≥ 18 years of age and admitted for severe COVID-19 pneumonia between March and June 2020 in 13 Hospitals in New Jersey, United States. Patients who received other formulation of corticosteroids were not included. Area under the receiver operating characteristics curves were performed to test for discriminatory ability of each inflammatory makers. Univariate and multivariate Cox regression assessed the association of variables to in hospital survival. RESULTS: Propensity matched sample (n = 759) between no methylprednisolone (n = 380) and methylprednisolone (n = 379) had 338 Whites, 102 Blacks, 61 Asian/Indians, and 251 non-Black non-White Hispanics. Compared to CRP, area under receiving operating characteristic curve for d-dimer in Hispanics (0.742) was statistically different (DeLong Test P = 0.0041). Multivariate cox regression showed that different variables in Blacks [age ≥ 60 years (HR = 3.71, P = 0.0281), mechanical ventilation (HR = 5.07, P = 0.0281) and creatinine ≥ 1.5 mg/dL (HR = 3.61, P = 0.0007)], Whites [cancer (HR = 1.68, P = 0.0213), qSOFA score of 1 (HR = 1.81, P = 0.0213), qSOFA score of 2 (HR = 5.16, P < 0.0001), qSOFA score of 3 (HR = 11.81, P < 0.0001) and creatinine ≥ 1.5 mg/dL (HR = 2.16, P = 0.0006)], Hispanics [hypertension (HR = 2.52, P = 0.0007), cancer (HR = 2.99, P = 0.0244 and D-dimer ≥ 2 mcg/mL (HR = 2.22, P = 0.0077)], and Asian/Indians [ chronic kidney disease (HR = 6.36, P = 0.0031) and CRP > 20 mg/L (HR = 5.02, P = 0.0032)] were statistically significant for mortality. Low dose and high dose methylprednisolone were significantly associated with prolonged survival in Whites [low dose (HR = 0.37, P < 0.0001) and high dose (HR = 0.48, P < 0.0183)] and Asian/Indians [low dose (HR = 0.13, P = 0.0101) and high dose (HR = 0.15, P = 0.01)]. However, high dose was not associated with improved survival compared to low dose. Methylprednisolone was not associated with prolonged survival in Blacks and Hispanics. CONCLUSION: Racial/Ethnic disparities with inflammatory markers preclude the use of one marker as a predictor of survival. Methylprednisolone is associated with prolonged survival in Asian/Indians and Whites.

Retarding performance of the vadose zone for nitrogen pollutants derived from municipal solid waste landfills in the red bed zone.

Nitrogen pollutants such as ammonia and nitrates cause soil and groundwater contamination at municipal solid waste landfill (MSWL) sites due to leachate leakage. Here, the migration of nitrogen pollutants in the vadose zone of the red bed (VZRB) at a MSWL site was studied by static adsorption batch experiments and one-dimensional simulated migration experiments. The results indicated that the soil in the red bed did not adsorb nitrates. Chemical adsorption and monolayer adsorption of the soil played dominant roles during ammonia adsorption in the VZRB, which was best fitted by the pseudo-second-order kinetic equation ( [Formula: see text] = 0.99) and the Langmuir model. The ammonia adsorption capacity of the soil was the highest (Qm = 2.041 mg·g-1) at 318 K. It was due to the endothermic and non-spontaneous chemical adsorption of ammonia, whose enthalpy change (ΔH) reached 20.995 kJ·mol-1 and Gibbs free energy ranged from 8.469 to 8.706 kJ·mol-1. Chloride penetration tests indicated that the diffusion coefficient and migration speed reached 0.0515 cm2·h-1 and 0.0833 cm·h-1, respectively, in the clay layer under the MSWL sites. The average hysteresis diffusion coefficients of ammonia in the simulated soil columns leached by ammonium chloride solution (SSCAC) and by the leachate from MSWL (SSCL) were 1.129 and 1.400, respectively. After the leaching experiments, the clay pore structure was saturated, and the specific surface area decreased. The absorption peak intensities of clay functional groups, including carboxyl, alkyne, and hydroxyl groups, were reduced. The ammonia content in the soil of SSCAC decreased from the top (14.51 mg·kg-1) to the bottom (3.14 mg·kg-1) and in the SSCL from 24.96 mg·kg-1 to 5.05 mg·kg-1, respectively. Thus, the impermeable clay layer and VZRB helped in retardation of ammonia leakage from MSWL sites. This was due to the blockage of seepage, ammonia mechanical filtration, ammonia monolayer chemical adsorption, and the reaction between the functional groups and ammonia in the VZRB underneath the MSWL sites.

Discharged COVID-19 patients testing positive again for SARS-CoV-2 RNA: A minireview of published studies from China.

In the ongoing coronavirus disease 2019 (COVID-19) pandemic, one potential cause of concern is that some discharged COVID-19 patients are testing positive again for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) RNA. To better understand what is happening and to provide public health policy planners and clinicians timely information, we have searched and reviewed published studies about discharged patients testing positive again for the SARS-CoV-2 RNA. Our search found 12 reports, all of which described patients in China. Our review of these reports indicates the presence of discharged patients who remain asymptomatic but test positive. However, it is unclear whether they are contagious because a positive reverse transcriptase - polymerase chain reaction (RT- PCR) test does not necessarily indicate the presence of replicating and transmissible virus. Our review suggests the need for timely, parallel testing of different samples, including, for example, fecal specimens, from COVID-19 patients before and after they are discharged from hospitals.

Field Test of Twin-Field Quantum Key Distribution through Sending-or-Not-Sending over 428 km.

Quantum key distribution endows people with information-theoretical security in communications. Twin-field quantum key distribution (TF-QKD) has attracted considerable attention because of its outstanding key rates over long distances. Recently, several demonstrations of TF-QKD have been realized. Nevertheless, those experiments are implemented in the laboratory, and therefore a critical question remains about whether the TF-QKD is feasible in real-world circumstances. Here, by adopting the sending-or-not-sending twin-field QKD (SNS-TF-QKD) with the method of actively odd parity pairing (AOPP), we demonstrate a field-test QKD over 428 km of deployed commercial fiber and two users are physically separated by about 300 km in a straight line. To this end, we explicitly measure the relevant properties of the deployed fiber and develop a carefully designed system with high stability. The secure key rate we achieved breaks the absolute key rate limit of repeaterless QKD. The result provides a new distance record for the field test of both TF-QKD and all types of fiber-based QKD systems. Our work bridges the gap of QKD between laboratory demonstrations and practical applications and paves the way for an intercity QKD network with measurement-device-independent security.

Factors influencing groundwater contamination near municipal solid waste landfill sites in the Qinghai-Tibetan plateau.

Effective management of municipal solid waste (MSW) is essential for the conservation of ecosystems in the Qinghai-Tibetan Plateau (QTP). Considering the landfill is the major method of MSW management, the factors influencing groundwater contamination near MSW landfill sites in the QTP were studied, based on field investigations, environmental impact assessment, and meteorological and hydrogeological analyses. Results indicated that the groundwater was contaminated heavily by nitrate (PI = 7.5), particularly in the landfill without an anti-seepage system, followed by nitrite (PI = 3.5) and heavy metals including arsenic (PI = 4.1) and hexavalent chromium (PI = 2.8). Total hardness, total dissolved solids, nitrate, and lead in the groundwater near the investigated landfill sites were significantly different between the monsoon and the cold seasons. Both the rainfall infiltration and the leachate infiltration were considerably limited by environmental characteristics in the QTP, including high evaporation, low rainfall, and the presence of permafrost. Soil sample contamination near landfill sites was considered as moderate (28.6% of the soil samples) and moderate to heavy (71.4% of the soil samples), based on the geoaccumulation index of mercury. However, comparatively low generation and concentrations of leachate and good topsoil quality (PI = 0.84) reduced the quantity of pollutants infiltrating into the groundwater. The alkaline leachate (pH = 7.45-9.23) and soil (pH = 7.08-8.72) also considerably decreased the concentrations of contaminants dissolved in the infiltrated rainfall and leachate. Additionally, low groundwater level can delay preferential flow and enhance attenuation. Therefore, the groundwater contamination near the landfill sites was simply point pollution, which was influenced by leachate, soil, climate, and hydrogeology characteristics in the QTP. The anti-seepage system is a potential strategy for use in the prevention of groundwater contamination by MSW landfills in the QTP.

Clinical Outcomes of COVID-19 Patients with Pre-existing, Compromised Immune Systems: A Review of Case Reports.

In the ongoing COVID-19 pandemic, all COVID-19 patients are naïve patients as it is the first-time humans have been exposed to the SARS-CoV-2 virus. As with exposure to many viruses, individuals with pre-existing, compromised immune systems may be at increased risk of developing severe symptoms and/or dying because of (SARS-CoV-2) infection. To learn more about such individuals, we conducted a search and review of published reports on the clinical characteristics and outcomes of COVID-19 patients with pre-existing, compromised immune systems. Here we present our review of patients who possess pre-existing primary antibody deficiency (PAD) and those who are organ transplant recipients on maintenance immunosuppressants. Our review indicates different clinical outcomes for the patients with pre-existing PAD, depending on the underlying causes. For organ transplant recipients, drug-induced immune suppression alone does not appear to enhance COVID-19 mortality risk - rather, advanced age, comorbidities, and the development of secondary complications appears required.

Identification of nitrogen-sources in an aquifer beneath a municipal solid waste landfill in the vicinity of multiple pollutant sources.

Nitrogen contamination of groundwater has become a global issue and has aroused considerable concern among authorities. However, it is difficult to trace nitrogen sources in settings where a municipal solid waste (MSW) landfill site co-exists with intensive agriculture and other human activities. Therefore, a field investigation that combined a statistical analysis (factor analysis: FA) and hydrochemical analysis was designed and undertaken to identify nitrogen-pollutant sources in the shallow groundwater beneath an MSW landfill near to an agricultural area and human settlement. The results of the case study showed that nitrate was the specific pollutant produced by agricultural non-point-sources (Pbi = 15.5) and domestic pollution sources (Pbi = 41.0). The total phosphorus (Pbi = 37.2) and organic matter (Pbi = 16.6) were the specific pollutants released by the aquaculture and animal husbandry point-sources, and chloride (Pbi = 75.4) and organic matter (Pbi = 16.1) were the specific pollutants produced by the landfill. In the investigated area, the domestic pollution sources and agricultural non-point-sources were the most likely sources of nitrate contamination in the shallow aquifer. However, the landfill source and the aquaculture and animal husbandry point sources were the most likely sources of ammonium contamination. The combined method used in this study could successfully identify the nitrogen pollution sources in the shallow groundwater beneath an MSW landfill located in the vicinity of multiple pollutant sources. The method could be used to improve the control of nitrogen contamination and the management of groundwater quality.

And-1 coordinates with Claspin for efficient Chk1 activation in response to replication stress.

The replisome is important for DNA replication checkpoint activation, but how specific components of the replisome coordinate with ATR to activate Chk1 in human cells remains largely unknown. Here, we demonstrate that And-1, a replisome component, acts together with ATR to activate Chk1. And-1 is phosphorylated at T826 by ATR following replication stress, and this phosphorylation is required for And-1 to accumulate at the damage sites, where And-1 promotes the interaction between Claspin and Chk1, thereby stimulating efficient Chk1 activation by ATR. Significantly, And-1 binds directly to ssDNA and facilitates the association of Claspin with ssDNA. Furthermore, And-1 associates with replication forks and is required for the recovery of stalled forks. These studies establish a novel ATR-And-1 axis as an important regulator for efficient Chk1 activation and reveal a novel mechanism of how the replisome regulates the replication checkpoint and genomic stability.

And-1 is required for homologous recombination repair by regulating DNA end resection.

Homologous recombination (HR) is a major mechanism to repair DNA double-strand breaks (DSBs). Although tumor suppressor CtIP is critical for DSB end resection, a key initial event of HR repair, the mechanism regulating the recruitment of CtIP to DSB sites remains largely unknown. Here, we show that acidic nucleoplasmic DNA-binding protein 1 (And-1) forms complexes with CtIP as well as other repair proteins, and is essential for HR repair by regulating DSB end resection. Furthermore, And-1 is recruited to DNA DSB sites in a manner dependent on MDC1, BRCA1 and ATM, down-regulation of And-1 impairs end resection by reducing the recruitment of CtIP to damage sites, and considerably reduces Chk1 activation and other damage response during HR repair. These findings collectively demonstrate a hitherto unknown role of MDC1→And-1→CtIP axis that regulates CtIP-mediated DNA end resection and cellular response to DSBs.

Dye removal by eco-friendly physically cross-linked double network polymer hydrogel beads and their functionalized composites.

Hydrogels have attracted large attention in wastewater treatment fields due to their low-cost and good interaction with pollutants, among which novel double network hydrogel is an outstanding class. To expand the application of double network hydrogel in water treatment, in this study, eco-friendly physically cross-linked double network polymer hydrogel beads (DAP) are prepared and studied in depth on the mechanism of Methylene Blue (MB) adsorption; and then the polymer hydrogels are further functionalized by inorganic materials. MB adsorption on DAP favors alkaline condition which is due to the increase of electrostatic attraction and adsorption site, and it reaches equilibrium within 10 hr, which is faster than that of the single network hydrogel beads (SAP). Through thermodynamics study, the process shows to be an exothermic and spontaneous process. The adsorption isotherms are well fitted by Langmuir model, with a maximum monolayer adsorption capacity of 1437.48 mg/g, which is larger than SAP (1255.75 mg/g). After being functionalized with common inorganic materials including activated carbon, Fe3O4 and graphene oxide (GO), the composites show to have larger pore sizes and have obvious increases in adsorption capacity especially the one contains GO. Then the composites contains Fe3O4 are used as heterogeneous Fenton catalyst which shows to have excellent performance in MB degradation. The results indicate the potential of polymer double network to be functionalized in environmental areas.

Catalytic Generation of C1 Ammonium Enolates from Halides and CO for Asymmetric Cascade Reactions.

A general strategy for the design of asymmetric cascade reactions using readily available halides and carbon monoxide (CO) as substrates is developed. The key is the catalytic generation of C1-ammonium enolates for the subsequent asymmetric cascade reactions through the combination of palladium-catalyzed carbonylation and chiral Lewis base catalysis. Utilizing this strategy, we have established asymmetric formal [1+1+4] and [1+1+2] reactions to afford chiral dihydropyridones and ß-lactams with high yields and high enantio- and diastereoselectivities.

Assembly of Tetrahydropyran Derivatives from Aldehydes, Allylboronates, and Syngas by Asymmetric Relay Catalytic Cascade Reaction.

An efficient synthesis of highly enantio-enriched tetrahydropyrans from readily available aldehydes, allylboronates, and syngas has been established by multiply relay catalysis of rhodium and chiral phosphoric acid. The cascade reaction integrates the asymmetric allylboration of aldehydes and alkene hydroformylation, providing a structurally diverse range of products with different workup procedures. The concise synthesis of key chiral building blocks to access herboxidiene and leucascandrolide A demonstrates the high synthetic utility of this method. The cascade reaction employing alkenes to replace aldehydes was also successful.