Diversity-Oriented Catalytic Asymmetric Dearomatization of Indoles with o-Quinone Diimides.

Herein, the first diversity-oriented catalytic asymmetric dearomatization of indoles with o-quinone diimides (o-QDIs) is reported. The catalytic asymmetric dearomatization (CADA) of indoles is one of the research focuses in terms of the structural and biological importance of dearomatized indole derivatives. Although great achievements have been made in target-oriented CADA reactions, diversity-oriented CADA reactions are regarded as more challenging and remain elusive due to the lack of synthons featuring multiple reaction sites and the difficulty in precise control of chemo-, regio-, and enantio-selectivity. In this work, o-QDIs are employed as a versatile building block, enabling the chemo-divergent dearomative arylation and [4 + 2] cycloaddition reactions of indoles. Under the catalysis of chiral phosphoric acid and mild conditions, various indolenines, furoindolines/pyrroloindolines, and six-membered-ring fused indolines are collectively prepared in good yields with excellent enantioselectivities. This diversity-oriented synthesis protocol enriches the o-quinone chemistry and offers new opportunities for CADA reactions.

Catalytic asymmetric dearomatization of phenols via divergent intermolecular (3 + 2) and alkylation reactions.

The catalytic asymmetric dearomatization (CADA) reaction has proved to be a powerful protocol for rapid assembly of valuable three-dimensional cyclic compounds from readily available planar aromatics. In contrast to the well-studied indoles and naphthols, phenols have been considered challenging substrates for intermolecular CADA reactions due to the combination of strong aromaticity and potential regioselectivity issue over the multiple nucleophilic sites (O, C2 as well as C4). Reported herein are the chiral phosphoric acid-catalyzed divergent intermolecular CADA reactions of common phenols with azoalkenes, which deliver the tetrahydroindolone and cyclohexadienone products bearing an all-carbon quaternary stereogenic center in good yields with excellent ee values. Notably, simply adjusting the reaction temperature leads to the chemo-divergent intermolecular (3 + 2) and alkylation dearomatization reactions. Moreover, the stereo-divergent synthesis of four possible stereoisomers in a kind has been achieved via changing the sequence of catalyst enantiomers.

Dinuclear Zinc-Catalyzed Asymmetric Desymmetrization of Cyclopentendiones: Access to Functional Cyclopentanediones Bearing an All-carbon Quaternary Stereocenter.

The success in the identification of the two enantioisomeric surfaces of electrophiles by dinuclear zinc catalysts is disclosed. This protocol realizes a dinuclear zinc-cocatalyzed desymmetrization of cyclopentendiones using α-hydroxy aryl ketones as nucleophiles through Michael addition reaction. Under mild conditions, a series of functional cyclopentanediones bearing multiple stereogenic centers including an all-carbon quaternary stereocenter, were obtained in moderate to good yields with excellent stereoselectivities.

Zn-ProPhenol catalyzed asymmetric inverse-electron-demand Diels-Alder reaction.

The first Zn-ProPhenol catalyzed asymmetric inverse-electron-demand Diels-Alder reaction has been accomplished. This protocol was carried out by a dual-activation mode under mild conditions, allowing the preparation of various biologically important dihydropyrans in good yields with excellent stereoselectivities.

Novel 2-Amino-1,4-Naphthoquinone Derivatives Induce A549 Cell Death through Autophagy.

A series of 1,4-naphthoquinone derivatives containing were synthesized as anti-cancer agents and the crystal structure of compound 5a was confirmed by X-ray diffraction. In addition, the inhibitory activities against four cancer cell lines (HepG2, A549, K562, and PC-3) were tested, respectively, and compound 5i showed significant cytotoxicity on the A549 cell line with the IC50 of 6.15 µM. Surprisingly, in the following preliminary biological experiments, we found that compound 5i induced autophagy by promoting the recycling of EGFR and signal transduction in the A549 cell, resulting in the activation of the EGFR signal pathway. The potential binding pattern between compound 5i and EGFR tyrosine kinase (PDB ID: 1M17) was also identified by molecular docking. Our research paves the way for further studies and the development of novel and powerful anti-cancer drugs.

Catalytic asymmetric de novo construction of 4-pyrrolin-2-ones via intermolecular formal [3+2] cycloaddition of azoalkenes with azlactones.

The chiral phosphoric acid-catalyzed asymmetric intermolecular formal [3+2] cycloaddition of azoalkenes with azlactones has been established. This convergent protocol leads to a facile and enantioselective de novo construction of a wide range of fully substituted 4-pyrrolin-2-ones bearing a fully substituted carbon atom in good yields and with excellent enantioselectivities (26 examples, 72-95% yields and 87-99% ee).

Plasma-Membrane-Localized Transporter NREET1 is Responsible for Rare Earth Element Uptake in Hyperaccumulator Dicranopteris linearis.

Rare earth elements (REEs) are critical for numerous modern technologies, and demand is increasing globally; however, production steps are resource-intensive and environmentally damaging. Some plant species are able to hyperaccumulate REEs, and understanding the biology behind this phenomenon could play a pivotal role in developing more environmentally friendly REE recovery technologies. Here, we identified a REE transporter NRAMP REE Transporter 1 (NREET1) from the REE hyperaccumulator fern Dicranopteris linearis. Although NREET1 belongs to the natural resistance-associated macrophage protein (NRAMP) family, it shares a low similarity with other NRAMP members. When expressed in yeast, NREET1 exhibited REE transport capacity, but it could not transport divalent metals, such as zinc, nickel, manganese, or iron. NREET1 is mainly expressed in D. linearis roots and predominantly localized in the plasma membrane. Expression studies in Arabidopsis thaliana revealed that NREET1 functions as a transporter mediating REE uptake and transfer from root cell walls into the cytoplasm. Moreover, NREET1 has a higher affinity for transporting light REEs compared to heavy REEs, which is consistent to the preferential enrichment of light REEs in field-grown D. linearis. We therefore conclude that NREET1 may play an important role in the uptake and consequently hyperaccumulation of REEs in D. linearis. These findings lay the foundation for the use of synthetic biology techniques to design and produce sustainable, plant-based REE recovery systems.

The Distribution Pattern and Species Richness of Scorpionflies (Mecoptera: Panorpidae).

The uneven distribution of species diversity on earth, with mountainous regions housing half of the high species diversity areas, makes mountain ecosystems vital to biodiversity conservation. The Panorpidae are ecological indicators, ideal for studying the impact of climate change on potential insect distribution. This study examines the impact of environmental factors on the distribution of the Panorpidae and analyzes how their distribution has changed over three historical periods, the Last Interglacial (LIG), the Last Glacial Maximum (LGM), and Current. The MaxEnt model is used to predict the potential distribution area of Panorpidae based on global distribution data. The results show that precipitation and elevation are the primary factors affecting species richness, and the suitable areas for Panorpidae are distributed in southeastern North America, Europe, and southeastern Asia. Throughout the three historical periods, there was an initial increase followed by a decrease in the area of suitable habitats. During the LGM period, there was a maximum range of suitable habitats for cool-adapted insects, such as scorpionflies. Under the scenarios of global warming, the suitable habitats for Panorpidae would shrink, posing a challenge to the conservation of biodiversity. The study provides insights into the potential geographic range of Panorpidae and helps understand the impact of climate change on their distribution.

Zinc-Catalyzed Asymmetric Cascade Michael/Acyl Transfer Reaction between α-Hydroxy Aryl Ketones and Enynones.

We described herein a neoteric enantioselective cascade Michael/acyl transfer reaction of enynones and α-hydroxy aryl ketones catalyzed by dinuclear zinc cooperative catalysis. A series of structurally diverse chiral 1,5-dicarbonyl compounds were synthesized in good yields with excellent stereoselectivities. This strategy features broad substrate scope, high atom economy, as well as enynones as efficient electrophilic acyl transfer reagents in asymmetric cascade reactions for the first time.

Zinc-Catalyzed Enantioselective [3 + 3] Annulation for Synthesis of Chiral Spiro[indoline-3,4'-thiopyrano[2,3-b]indole] Derivatives.

With a dinuclear zinc-ProPhenol complex as a catalyst, an efficient and novel [3 + 3] annulation of indoline-2-thiones and isatylidene malononitriles has been successfully developed via the Brønsted base and Lewis acid cooperative activation model. This practical methodology gives access to a broad range of chiral spiro[indoline-3,4'-thiopyrano[2,3-b]indole] derivatives in good yields with excellent levels of enantioselectivities (up to 88% yield and 99% ee).

Manual acupuncture for neuromusculoskeletal disorders: The selection of stimulation parameters and corresponding effects.

As a minimally invasive method of physical stimulation, manual acupuncture (MA) is used globally as a sort of therapy for neuromusculoskeletal disorders. In addition to selecting appropriate acupoints, acupuncturists should also determine the stimulation parameters of needling, such as the manipulation (lifting-thrusting or twirling), needling amplitude, velocity, and stimulation time. At present, most studies focus on acupoint combination and mechanism of MA, the relationship between stimulation parameters and their therapeutic effects, as well as the influence on mechanism of action are relatively scattered, and lack of systematic summary and analysis. This paper reviewed the three types of stimulation parameters of MA, their common options and values, corresponding effects and potential mechanisms of action. The purpose of such efforts is to provide a useful reference for the dose-effect relationship of MA and the quantification and standardization of its clinical treatment of neuromusculoskeletal disorders to further promote the application of acupuncture in the world.

Measurement of the Thermic Effect of Food in a Chinese Mixed Diet in Young People / 生物医学与环境科学（英文）

OBJECTIVE@#To determine the thermic effect of food (TEF) in a Chinese mixed diet in young people.@*METHODS@#During the study, the participants were weighed and examined for body composition every morning. The total energy expenditure (TEE) of the participants was measured by the doubly labeled water method for 7 days, and during this period, basal energy expenditure was measured by indirect calorimetry and physical activity energy expenditure was measured by an accelerometer. The value obtained by subtracting basal energy expenditure and physical activity energy expenditure from TEE was used to calculate TEF.@*RESULTS@#Twenty healthy young students (18-30 years; 10 male) participated in the study. The energy intake of the participants was not significantly different from the Chinese Dietary Reference Intake of energy ( P > 0.05). The percentage of energy from protein, fat and carbohydrate were all in the normal range. The intakes of fruits, milk and dietary fiber of the participants were significantly lower than those in the Chinese Dietary Guidelines ( P < 0.05). There was no significant difference in the body weight of the participants during the experiment ( P > 0.05). When adjusted for body weight, there was no significant difference in either TEE or basal energy expenditure between the male and female participants ( P > 0.05). In addition, there was no significant difference in physical activity energy expenditure and TEF between the male and female participants ( P > 0.05). The percentage of TEF in TEE was 8.73%.@*CONCLUSION@#The percentage of TEF in TEE in a Chinese mixed diet in young people was significantly lower than 10% ( P < 0.001). A value of 10% is usually considered to be the TEF in mixed diets as a percentage of TEE.

The neural basis underlying primary dysmenorrhea: evidence from neuroimaging and animal model studies / 生理学报

Primary dysmenorrhea (PDM), cyclic menstrual pain in the absence of pelvic anomalies, is characterized by acute and chronic gynecological pain disorders in childbearing age women. PDM strongly affects the quality of life of patients and leads to economic losses. PDM generally do not receive radical treatment and often develop into other chronic pain disorders later in life. The clinical treatment status of PDM, the epidemiology of PDM and chronic pain comorbidities, and the abnormal physiological and psychological characteristics of patients with PDM suggest that PDM not only is related to the inflammation around the uterus, but also may be related to the abnormal pain processing and regulation function of patients' central system. Therefore, exploring the brain neural mechanism of PDM is indispensable and important to understand the pathological mechanism of PDM, and is also a hotspot of brain science research in recent years, which will bring new inspiration to explore the target of PDM intervention. Based on the progress of the neural mechanism of PDM, this paper systematically summarizes the evidence from neuroimaging and animal model studies.

Risk factors for urinary tract infection after a spinal cord injury / 中华物理医学与康复杂志

Objective:To explore the risk factors for urinary tract infection (UTI) after a spinal cord injury (SCI).Methods:The medical records of 403 SCI patients were analyzed retrospectively. They were divided into UTI group and no-UTI group according to whether they had a UTI at admission. Gender, age, cause of injury, injury level of the spinal cord, voluntary anal contraction, time from injury to admission, American Spinal Injury Association (ASIA) grade, axillary temperature at admission, complications at admission (diabetes, hypertension, fracture of the pelvis, pressure sores or anemia), white blood cell count and urinary bacteria were compared between the two groups. Binary logistic regression was used to highlight the risk factors for a UTI after an SCI.Results:Of the 354 patients included in the final analysis, 62 (17.51%) had a UTI at admission. The regression showed that UTI after an SCI was closely related to an inability to voluntarily contract the anus, anemia, elevated white blood cell count and a high level of bacteria in the urine.Conclusions:Inability to contract the anus, fever, anemia and an elevated white blood cell count are independent indicators of a UTI after an SCI. A temperature ≥37.3°C is a simple indicator of a concentration of bacteria in the urine ≥1266/μL.

Risk factors for deep vein thrombosis after a spinal cord injury: A retrospective study / 中华物理医学与康复杂志

Objective:To explore the risk factors for lower extremity deep vein thrombosis (DVT) in patients with a spinal cord injury (SCI).Methods:The medical records of 276 hospitalized SCI patients were analyzed retrospectively. They were divided into a DVT group ( n=63) and a no-DVT group ( n=213). Gender, age, blood type, smoking history, surgical history, the time from SCI to admission, cause of SCI, fracture, SCI segments, American Spinal Cord Injury Association grade and complications were compared between the two groups. Binomial logistic regression was used to isolate the risk factors for lower extremity DVT among such patients. Results:Among 84% of the 63 with a lower extremity DVT, it was a calf muscle venous thrombosis. Anemia, hyponatremia and time from SCI to admission (which ranged from 74 to 195 days) were the most serious DVT risk factors.Conclusions:SCI patients are of high risk for DVT, with anemia and hyponatremia being independent risk factors.

Clinical and molecular biological characterization of patients with accelerated chronic lymphocytic leukemia / 中华血液学杂志

Objective: To investigate the clinical and molecular biological characteristics of patients with accelerated chronic lymphocytic leukemia (aCLL) . Methods: From January 2020 to October 2022, the data of 13 patients diagnosed with aCLL at The First Affiliated Hospital of Nanjing Medical University were retrospectively analyzed to explore the clinical and molecular biological characteristics of aCLL. Results: The median age of the patients was 54 (35-72) years. Prior to aCLL, five patients received no treatment for CLL/small lymphocytic lymphoma (SLL), while the other patients received treatment, predominantly with BTK inhibitors. The patients were diagnosed with aCLL through pathological confirmation upon disease progression. Six patients exhibited bulky disease (lesions with a maximum diameter ≥5 cm). Positron emission tomography (PET) -computed tomography (CT) images revealed metabolic heterogeneity, both between and within lesions, and the median maximum standardized uptake value (SUVmax) of the lesion with the most elevated metabolic activity was 6.96 (2.51-11.90). Patients with unmutated IGHV CLL accounted for 76.9% (10/13), and the most frequent genetic and molecular aberrations included +12 [3/7 (42.9% ) ], ATM mutation [6/12 (50% ) ], and NOTCH1 mutation [6/12 (50% ) ]. Twelve patients received subsequent treatment. The overall response rate was 91.7%, and the complete response rate was 58.3%. Five patients experienced disease progression, among which two patients developed Richter transformation. Patients with aCLL with KRAS mutation had worse progression-free survival (7.0 month vs 26.3 months, P=0.015) . Conclusion: Patients with aCLL exhibited a clinically aggressive course, often accompanied by unfavorable prognostic factors, including unmutated IGHV, +12, ATM mutation, and NOTCH1 mutation. Patients with CLL/SLL with clinical suspicion of disease progression, especially those with bulky disease and PET-CT SUVmax ≥5, should undergo biopsy at the site of highest metabolic uptake to establish a definitive pathological diagnosis.

Research advances on the role of ACSL3 in the atherosclerosis / 生理学报

Lipids droplets are organelles that store neutral lipids and are closely related to lipid accumulation. Long chain acyl-coenzyme A synthetase 3 (ACSL3) is a lipid droplet-associated protein mainly distributed in the cell membrane, endoplasmic reticulum, and intracellular lipid droplets, and its distribution depends on cell type and fatty acid supply. ACSL3 is a key regulator of fatty acid metabolism that is closely related to intracellular lipid accumulation, and plays an important role in various pathophysiological processes such as lipid droplet synthesis and lipid metabolism, cellular inflammation, and ferroptosis. This paper mainly reviews the role of ACSL3 in lipid synthesis, ferroptosis, and inflammatory response, with focus on the mechanism of its role in lipid accumulation in atherosclerosis, and provides new ideas for exploring potential therapeutic targets in atherosclerotic diseases.

Progress in the classification of hereditary dentin disorders and clinical management strategies / 中华口腔医学杂志

Heterogeneous mutations in dentin sialophosphoprotein (DSPP) gene, which is located on autosome 4, are associated with hereditary dentin developmental disorders. According to the new classification proposed by de La Dure-Molla et al, diseases caused by DSPP gene mutations mainly manifested as abnormal dentin development are collectively referred to as dentinogenesis imperfecta (DI), including dentin dysplasia type Ⅱ (DD-Ⅱ), dentinogenesis imperfecta type Ⅱ (DGI-Ⅱ) and dentinogenesis imperfecta type Ⅲ (DGI-Ⅲ) in Shields classification. And dentin dysplasia type Ⅰ (DD-Ⅰ) in Shields classification is redesignated as radicular dentin dysplasia. In this paper, progress in the classification, clinical characteristics and genetic mechanisms of DI are reviewed. This paper also provides clinical management and treatment strategies for patients suffering DI.

Surgical treatment methods and classification of proximal clavicle fracture / 中国骨伤

OBJECTIVE@#To summarize the surgical treatment of different proximal clavicle fractures, and discuss the classification of proximal clavicle fractures.@*METHODS@#Total of 24 patients with displaced proximal clavicle fractures were treated from January 2017 to December 2020 including 16 males and 8 females, aged 28 to 66 years old. Among them, 20 cases were fresh fractures and 4 cases were old fractures. According to the Edinburgh classification, 14 cases were type 1B1 fractures and 10 cases were type 1B2 fractures. The different internal fixation methods were selected for internal fixation treatment according to different fracture types.The operation time, blood loss, preoperative and postoperative displacement difference, fracture healing time and Rockwood scoring system were recorded.@*RESULTS@#All patients were followed up for 12 to 24 months. There were no patients with infection or loss of reduction after the operation. Three patients had internal fixation failure after operation, and the internal fixation device was removed. Results The operation time was 30 to 65 min, and the blood loss was 15 to 40 ml. No important nerves, blood vessels, or organs were damaged. The imaging healing time was 3 to 6 months. According to the Rockwood functional score, the total score was (13.50±1.86), pain (2.57±0.50), range of motion (2.78±0.41), muscle strength (2.93±0.28), restricted daily activity (2.85±0.35), subjective results (2.63±0.61);the results were excellent in 20 cases, good in 3 cases, fair in 1 case.@*CONCLUSION@#Proximal clavicular fracture is a type of fracture with low incidence. According to different fracture types, different internal fixation methods and treatment methods can be selected, and satisfactory surgical results can be achieved.

Finite element analysis of PMMA bone cement reinforced screw plate fixation for osteoporotic proximal humeral fracture / 中国骨伤

OBJECTIVE@#With the help of finite element analysis, to explore the effect of proximal humeral bone cement enhanced screw plate fixation on the stability of internal fixation of osteoporotic proximal humeral fracture.@*METHODS@#The digital model of unstable proximal humeral fracture with metaphyseal bone defect was made, and the finite element models of proximal humeral fracture bone cement enhanced screw plate fixation and common screw plate fixation were established respectively. The stress of cancellous bone around the screw, the overall stiffness, the maximum stress of the plate and the maximum stress of the screw were analyzed.@*RESULTS@#The maximum stresses of cancellous bone around 6 screws at the head of proximal humeral with bone cement enhanced screw plate fixation were 1.07 MPa for No.1 nail, 0.43 MPa for No.2 nail, 1.16 MPa for No.3 nail, 0.34 MPa for No.4 nail, 1.99 MPa for No.5 nail and 1.57 MPa for No.6 nail. These with common screw plate fixation were:2.68 MPa for No.1 nail, 0.67 MPa for No.2 nail, 4.37 MPa for No.3 nail, 0.75 MPa for No.4 nail, 3.30 MPa for No.5 nail and 2.47 MPa for No.6 nail. Overall stiffness of the two models is 448 N/mm for bone cement structure and 434 N/mm for common structure. The maximum stress of plate appears in the joint hole:701MPa for bone cement structure and 42 0MPa for common structure. The maximum stress of screws appeared at the tail end of No.4 nail:284 MPa for bone cement structure and 240.8 MPa for common structure.@*CONCLUSION@#Through finite element analysis, it is proved that the proximal humerus bone cement enhanced screw plate fixation of osteoporotic proximal humeral fracture can effectively reduce the stress of cancellous bone around the screw and enhance the initial stability after fracture operation, thus preventing from penetrating out and humeral head collapsing.