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Electrons not only serve as a "reactant" in redox reactions but also play a role in "catalyzing" some chemical processes. Despite the significance and ubiquitousness of electron-induced chemistry, many related scientific issues still await further exploration, among which is the impact of molecular assembly. In this work, microscopic insights into the vital role of molecular assembly in tweaking the electron-induced surface chemistry are unfolded by combined scanning tunneling microscopy and density functional theory studies. It is shown that the selective dissociation of a C-Cl bond in 4,4â³-dichloro-1,1':3',1''-terphenyl (DCTP) on Cu(111) can be efficiently triggered by an electron injection via the STM tip into the unoccupied molecular orbital. The DCTP molecules are embedded in different assembly structures, including its self-assembly and coassemblies with Br adatoms. The energy threshold for the C-Cl bond cleavage increases as more Br adatoms stay close to the molecule, indicative of the sensitive response of the electron-induced surface reactivity of the C-Cl bond to the subtle change in the molecular assembly. Such a phenomenon is rationalized by the energy shift of the involved unoccupied molecular orbital of DCTP that is embedded in different assemblies. These findings shed new light on the tuning effect of molecular assembly on electron-induced reactions and introduce an efficient approach to precisely steer surface chemistry.
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Acetylene production from mixed α-olefins emerges as a potentially green and energy-efficient approach with significant scientific value in the selective cleavage of C-C bonds. On the Pd(100) surface, it is experimentally revealed that C2 to C4 α-olefins undergo selective thermal cleavage to form surface acetylene and hydrogen. The high selectivity toward acetylene is attributed to the 4-fold hollow sites which are adept at severing the terminal double bonds in α-olefins to produce acetylene. A challenge arises, however, because acetylene tends to stay at the Pd(100) surface. By using the surface alloying methodology with alien Au, the surface Pd d-band center has been successfully shifted away from the Fermi level to release surface-generated acetylene from α-olefins as a gaseous product. Our study actually provides a technological strategy to economically produce acetylene and hydrogen from α-olefins.
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Ketamine, an N-methyl-d-aspartate (NMDA) receptor antagonist, induces deficits in cognition and information processing following chronic abuse. Adolescent ketamine misuse represents a significant global public health issue; however, the neurodevelopmental mechanisms underlying this phenomenon remain largely elusive. This study investigated the long-term effects of sub-chronic ketamine (Ket) administration on the medial prefrontal cortex (mPFC) and associated behaviors. In this study, Ket administration during early adolescence displayed a reduced density of excitatory synapses on parvalbumin (PV) neurons persisting into adulthood. However, the synaptic development of excitatory pyramidal neurons was not affected by ketamine administration. Furthermore, the adult Ket group exhibited hyperexcitability and impaired socialization and working memory compared to the saline (Sal) administration group. These results strongly suggest that sub-chronic ketamine administration during adolescence results in functional deficits that persist into adulthood. Bioinformatic analysis indicated that the gene co-expression module1 (M1) decreased expression after ketamine exposure, which is crucial for synapse development in inhibitory neurons during adolescence. Collectively, these findings demonstrate that sub-chronic ketamine administration irreversibly impairs synaptic development, offering insights into potential new therapeutic strategies.
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Neurônios GABAérgicos , Interneurônios , Ketamina , Parvalbuminas , Córtex Pré-Frontal , Sinapses , Animais , Ketamina/farmacologia , Ketamina/administração & dosagem , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Parvalbuminas/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Masculino , Interneurônios/efeitos dos fármacos , Interneurônios/metabolismo , Camundongos , Neurônios GABAérgicos/efeitos dos fármacos , Neurônios GABAérgicos/metabolismo , Camundongos Endogâmicos C57BL , Antagonistas de Aminoácidos Excitatórios/farmacologiaRESUMO
Background Preoperative local-regional tumor staging of gastric cancer (GC) is critical for appropriate treatment planning. The comparative accuracy of multiparametric MRI (mpMRI) versus dual-energy CT (DECT) for staging of GC is not known. Purpose To compare the diagnostic accuracy of personalized mpMRI with that of DECT for local-regional T and N staging in patients with GC receiving curative surgical intervention. Materials and Methods Patients with GC who underwent gastric mpMRI and DECT before gastrectomy with lymphadenectomy were eligible for this single-center prospective noninferiority study between November 2021 and September 2022. mpMRI comprised T2-weighted imaging, multiorientational zoomed diffusion-weighted imaging, and extradimensional volumetric interpolated breath-hold examination dynamic contrast-enhanced imaging. Dual-phase DECT images were reconstructed at 40 keV and standard 120 kVp-like images. Using gastrectomy specimens as the reference standard, the diagnostic accuracy of mpMRI and DECT for T and N staging was compared by six radiologists in a pairwise blinded manner. Interreader agreement was assessed using the weighted κ and Kendall W statistics. The McNemar test was used for head-to-head accuracy comparisons between DECT and mpMRI. Results This study included 202 participants (mean age, 62 years ± 11 [SD]; 145 male). The interreader agreement of the six readers for T and N staging of GC was excellent for both mpMRI (κ = 0.89 and 0.85, respectively) and DECT (κ = 0.86 and 0.84, respectively). Regardless of reader experience, higher accuracy was achieved with mpMRI than with DECT for both T (61%-77% vs 50%-64%; all P < .05) and N (54%-68% vs 51%-58%; P = .497-.005) staging, specifically T1 (83% vs 65%) and T4a (78% vs 68%) tumors and N1 (41% vs 24%) and N3 (64% vs 45%) nodules (all P < .05). Conclusion Personalized mpMRI was superior in T staging and noninferior or superior in N staging compared with DECT for patients with GC. Clinical trial registration no. NCT05508126 © RSNA, 2024 Supplemental material is available for this article. See also the editorial by Méndez and Martín-Garre in this issue.
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Estadiamento de Neoplasias , Neoplasias Gástricas , Tomografia Computadorizada por Raios X , Humanos , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/patologia , Neoplasias Gástricas/cirurgia , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Prospectivos , Idoso , Tomografia Computadorizada por Raios X/métodos , Gastrectomia/métodos , Adulto , Imageamento por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética Multiparamétrica/métodosRESUMO
Programmed cell death 1 (PD-1), a key immune checkpoint receptor, has been extensively studied for its role in regulating immune responses in cancer. However, recent research has unveiled a complex and dual role for PD-1 in tumorigenesis. While PD-1 is traditionally associated with immune cells, this article explores its expression in various cancer cells and its impact on cancer progression. PD-1's functions extend beyond immune regulation, as it has been found to both promote and suppress tumor growth, depending on the cancer type. These findings have significant implications for the future of cancer treatment and our understanding of the immune response in the context of cancer. This article calls for further research into the multifaceted roles of PD-1 to optimize its therapeutic potential and improve patient outcomes in the fight against cancer.
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Carcinogênese , Neoplasias , Receptor de Morte Celular Programada 1 , Humanos , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/imunologia , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Carcinogênese/imunologia , Carcinogênese/genética , Animais , Inibidores de Checkpoint Imunológico/uso terapêutico , Inibidores de Checkpoint Imunológico/farmacologiaRESUMO
Human adenovirus (HAdV) is a significant viral pathogen causing severe acute respiratory infections (SARIs) in children. To improve the understanding of type distribution and viral genetic characterization of HAdV in severe cases, this study enrolled 3404 pediatric SARI cases from eight provinces of China spanning 2017-2021, resulting in the acquisition of 112 HAdV strains. HAdV-type identification, based on three target genes (penton base, hexon, and fiber), confirmed the diversity of HAdV types in SARI cases. Twelve types were identified, including species B (HAdV-3, 7, 55), species C (HAdV-1, 2, 6, 89, 108, P89H5F5, Px1/Ps3H1F1, Px1/Ps3H5F5), and E (HAdV-4). Among these, HAdV-3 exhibited the highest detection rate (44.6%), followed by HAdV-7 (19.6%), HAdV-1 (12.5%), and HAdV-108 (9.8%). All HAdV-3, 7, 55, 4 in this study belonged to dominant lineages circulating worldwide, and the sequences of the three genes demonstrated significant conservation and stability. Concerning HAdV-C, excluding the novel type Px1/Ps3H1F1 found in this study, the other seven types were detected both in China and abroad, with HAdV-1 and HAdV-108 considered the two main types of HAdV-C prevalent in China. Two recombinant strains, including P89H5F5 and Px1/Ps3H1F1, could cause SARI as a single pathogen, warranting close monitoring and investigation for potential public health implications. In conclusion, 5 years of SARI surveillance in China provided crucial insights into HAdV-associated respiratory infections among hospitalized pediatric patients.
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Infecções por Adenovirus Humanos , Adenovírus Humanos , Infecções Respiratórias , Criança , Humanos , Adenovírus Humanos/genética , Análise de Sequência de DNA/métodos , Filogenia , Adenoviridae/genética , China/epidemiologia , Infecções Respiratórias/epidemiologiaRESUMO
This study employed structural and functional magnetic resonance imaging (MRI) to investigate changes in the function and structure of the cerebellum associated with gut-brain axis (GBA) regulation in patients diagnosed with Crohn's disease (CD). The study comprised 20 CD patients, including 12 with active disease (CD-A) and 8 in remission (CD-R), as well as 21 healthy controls. Voxel-based morphometry (VBM) was utilized for structural analysis of cerebellar gray matter volume, while independent component analysis (ICA) was applied for functional analysis of cerebellar functional connectivity (FC). The results showed significant GMV reduction in the left posterior cerebellar lobe across all CD patients compared to HCs, with more pronounced differences in the CD-A subgroup. Additionally, an increase in mean FC of the cerebellar network was observed in all CD patients, particularly in the CD-A subgroup, which demonstrated elevated FC in the vermis and bilateral posterior cerebellum. Correlation analysis revealed a positive relationship between cerebellar FC and the Crohn's Disease Activity Index (CDAI) and a trend toward a negative association with the reciprocal of the Self-rating Depression Scale (SDS) score in CD patients. The study's findings suggest that the cerebellum may play a role in the abnormal regulation of the GBA in CD patients, contributing to a better understanding of the neural mechanisms underlying CD and highlighting the cerebellum's potential role in modulating gut-brain interactions.
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The secondary structures of polypeptides, such as an α-helix and a ß-sheet, often impart specific properties and functions, making the regulation of their secondary structures of great significance. Particularly, water-soluble polypeptides bearing a ß-sheet conformation are rare and challenging to achieve. Here, a series of oligo(ethylene glycol)-modified lysine N-carboxylic anhydrides (EGmK-NCA, where m = 1-3) and the corresponding polymers EGmKn are synthesized, with urethane bonds as the linker between the side-chain EG and lysine. The secondary structure of EGmKn is delicately regulated by both m and n, the length (number of repeating units) of EG and the degree of polymerization (DP), respectively. Among them, EG2Kn adopts a ß-sheet conformation with good water solubility at an appropriate DP and forms physically cross-linked hydrogels at a concentration as low as 1 wt %. The secondary structures of EG1Kn can be tuned by DP, exhibiting either a ß-sheet or an α-helix, whereas EG3Kn appears to a adopt pure and stable α-helix with no dependence on DP. Compared to previous works reporting EG-modified lysine-derived polypeptides bearing exclusively an α-helix conformation, this work highlights the important and unexpected role of the urethane connecting unit and provides useful case studies for understanding the secondary structure of polypeptides.
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Peptídeos , Conformação Proteica em Folha beta , Solubilidade , Água , Peptídeos/química , Água/química , Polietilenoglicóis/química , Lisina/química , Hidrogéis/química , Etilenoglicol/química , Estrutura Secundária de Proteína , PolimerizaçãoRESUMO
BACKGROUND: Hepatitis B virus (HBV) infection can cause liver failure, while individuals with Acquired Immunodeficiency Virus Disease (AIDS) are highly susceptible to various opportunistic infections, which can occur concurrently. The treatment process is further complicated by the potential occurrence of immune reconstitution inflammatory syndrome (IRIS), which presents significant challenges and contributes to elevated mortality rates. CASE PRESENTATION: The 50-year-old male with a history of chronic hepatitis B and untreated human immunodeficiency virus (HIV) infection presented to the hospital with a mild cough and expectoration, revealing multi-drug resistant pulmonary tuberculosis (MDR-PTB), which was confirmed by XpertMTB/RIF PCR testing and tuberculosis culture of bronchoalveolar lavage fluid (BALF). The patient was treated with a regimen consisting of linezolid, moxifloxacin, cycloserine, pyrazinamide, and ethambutol for tuberculosis, as well as a combination of bictegravir/tenofovir alafenamide/emtricitabine (BIC/TAF/FTC) for HBV and HIV viral suppression. After three months of treatment, the patient discontinued all medications, leading to hepatitis B virus reactivation and subsequent liver failure. During the subsequent treatment for AIDS, HBV, and drug-resistant tuberculosis, the patient developed disseminated cryptococcal disease. The patient's condition worsened during treatment with liposomal amphotericin B and fluconazole, which was ultimately attributed to IRIS. Fortunately, the patient achieved successful recovery after appropriate management. CONCLUSION: Enhancing medical compliance is crucial for AIDS patients, particularly those co-infected with HBV, to prevent HBV reactivation and subsequent liver failure. Furthermore, conducting a comprehensive assessment of potential infections in patients before resuming antiviral therapy is essential to prevent the occurrence of IRIS. Early intervention plays a pivotal role in improving survival rates.
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Criptococose , Tuberculose Resistente a Múltiplos Medicamentos , Tuberculose Pulmonar , Humanos , Masculino , Pessoa de Meia-Idade , Criptococose/tratamento farmacológico , Criptococose/microbiologia , Criptococose/complicações , Tuberculose Pulmonar/tratamento farmacológico , Tuberculose Pulmonar/complicações , Tuberculose Resistente a Múltiplos Medicamentos/tratamento farmacológico , Tuberculose Resistente a Múltiplos Medicamentos/complicações , Falência Hepática/virologia , Síndrome da Imunodeficiência Adquirida/complicações , Síndrome da Imunodeficiência Adquirida/tratamento farmacológico , Hepatite B Crônica/complicações , Hepatite B Crônica/tratamento farmacológico , Coinfecção/tratamento farmacológico , Coinfecção/microbiologia , Coinfecção/virologia , Antituberculosos/uso terapêutico , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/tratamento farmacológico , Infecções Oportunistas Relacionadas com a AIDS/microbiologiaRESUMO
OBJECTIVE: The purpose of this study is to identify the presence of occult peritoneal metastasis (OPM) in patients with advanced gastric cancer (AGC) by using clinical characteristics and abdominopelvic computed tomography (CT) features. METHODS: This retrospective study included 66 patients with OPM and 111 patients without peritoneal metastasis (non-PM [NPM]) who underwent preoperative contrast-enhanced CT between January 2020 and December 2021. Occult PMs means PMs that are missed by CT but later diagnosed by laparoscopy or laparotomy. Patients with NPM means patients have neither PM nor other distant metastases, indicating there is no evidence of distant metastases in patients with AGC. Patients' clinical characteristics and CT features such as tumor marker, Borrmann IV, enhancement patterns, and pelvic ascites were observed by 2 experienced radiologists. Computed tomography features and clinical characteristics were combined to construct an indicator for identifying the presence of OPM in patients with AGC based on a logistic regression model. Receiver operating characteristic curves and the area under the receiver operating characteristic curve (AUC) were generated to assess the diagnostic performance of the combined indicator. RESULTS: Four independent predictors (Borrmann IV, pelvic ascites, carbohydrate antigen 125, and normalized arterial CT value) differed significantly between OPM and NPM and performed outstandingly in distinguishing patients with OPM from those without PM (AUC = 0.643-0.696). The combined indicator showed a higher AUC value than the independent risk factors (0.820 vs 0.643-0.696). CONCLUSIONS: The combined indicator based on abdominopelvic CT features and carbohydrate antigen 125 may assist clinicians in identifying the presence of CT OPMs in patients with AGC.
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AIMS: Neoadjuvant chemotherapy (NAC) is the primary preoperative therapy for breast cancer. The luminal subtype of breast cancer shows less NAC response than the basal subtype, with an inefficient NAC treatment effect. Understanding of the molecular and cellular mechanisms responsible for this chemoresistance is an important issue when determining optimal treatment. METHODS: Doxorubicin-induced apoptosis and ferroptosis was investigated using cytotoxicity, western blotting, and flow cytometry assays. The role of GATA3 in modulating doxorubicin-induced cell death was investigated both in vitro and in vivo. RNA-seq, qPCR, ChIP, and luciferase assay and association analyses were performed to investigate the regulation of CYB5R2 by GATA3. The function of GATA3 and CYB5R2 in regulating doxorubicin-induced ferroptosis was evaluated with iron, ROS, and lipid peroxidation detection assays. Immunohistochemistry was performed for results validation. RESULTS: Doxorubicin-induced basal breast cancer cell death is dependent on iron-mediated ferroptosis. Overexpression of the luminal signature transcriptional factor GATA3 mediates doxorubicin resistance. GATA3 promotes cell viability by decreasing ferroptosis-related gene CYB5R2 expression and by maintaining iron homeostasis. Analyzing data from the public and our cohorts demonstrates that GATA3 and CYB5R2 are associated with NAC response. CONCLUSIONS: GATA3 promotes doxorubicin resistance by inhibiting CYB5R2-mediated iron metabolism and ferroptosis. Therefore, patients with breast cancer who display high GATA3 expression do not benefit from doxorubicin-based NAC regimens.
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Neoplasias da Mama , Humanos , Feminino , Neoplasias da Mama/tratamento farmacológico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Doxorrubicina/farmacologia , Doxorrubicina/uso terapêutico , Apoptose , Ferro/metabolismo , Ferro/uso terapêutico , Catálise , Fator de Transcrição GATA3/genética , Fator de Transcrição GATA3/metabolismo , Fator de Transcrição GATA3/uso terapêuticoRESUMO
The aim of this work is to describe a rich set of acoustic transmission loss observations that were completed in a coastal environment. The data library, enumerated in detail and publicly posted, is comprised of pitch-catch acoustic transmission loss measurements along with concurrent high spatial resolution meteorological observations. The meteorological parameters include near-surface temperature profiles, vertical wind speed profiles in the acoustic propagation direction, and significant wave height estimates. The acoustic source is positioned on an anchored vessel such that the first several hundred meters of the acoustic range is over open water with one microphone array positioned at the shore. A second microphone array is placed several hundred meters inland along the same source-to-receiver heading. The path between the two acoustic arrays is uniform salt marsh vegetation. Observations were made during seven sessions, which represent a variety of atmospheric conditions. That variety of conditions allows for some experimental generalizations about transmission loss as a function of meteorological observations. These include (1) the relationship between vertical effective sound speed profile and transmission loss, and (2) the variability of acoustic pressure with turbulence over time and elevation.
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Grain size in rice (Oryza sativa L.) shapes yield and quality, but the underlying molecular mechanism is not fully understood. We functionally characterized GRAIN NUMBER AND LARGE GRAIN SIZE 44 (GNL44), encoding a RING-type protein that localizes to the cytoplasm. The gnl44 mutant has fewer but enlarged grains compared to the wild type. GNL44 is mainly expressed in panicles and developing grains. Grain chalkiness was higher in the gnl44 mutant than in the wild type, short-chain amylopectin content was lower, middle-chain amylopectin content was higher, and appearance quality was worse. The amylose content and gel consistency of gnl44 were lower, and protein content was higher compared to the wild type. Rapid Visco Analyzer results showed that the texture of cooked gnl44 rice changed, and that the taste value of gnl44 was lower, making the eating and cooking quality of gnl44 worse than that of the wild type. We used gnl44, qgl3, and gs3 monogenic and two-gene near-isogenic lines to study the effects of different combinations of genes affecting grain size on rice quality-related traits. Our results revealed additive effects for these three genes on grain quality. These findings enrich the genetic resources available for rice breeders.
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Oryza , Oryza/genética , Amilopectina , Amilose , Carbonato de Cálcio , Culinária , Grão Comestível/genéticaRESUMO
A 60-years-old man with previous hypertension was hospitalized because of colonoscopy revealed a cecal submucosal mass for community health examination 1 month ago. The patient has no symptoms such as poor appetite, fatigue, abdominal pain, diarrhea, nausea and vomiting. Laboratory tests and physical examination was unremarkable. A protrusion with multiple superficial small ulcers on the smooth surface measuring 1.5 × 2.0-cm was found beside the appendiceal orifice by colonoscopy. Abdominal computed tomography demonstrated a high-density mass without enhancement protruding towards the ileocecal cavity at the appendiceal orifice measured 1.5 × 1.8 cm. Laparoscopic ileocecal resection was performed because of appendiceal tumor couldn't be excluded and the patient's strong request. Pathology examination of the postoperative specimen revealed dilated appendix cavity with fecalith inside in the submucosal layer of the ileocecal region. The patient was diagnosed as appendiceal orifice submucosal fecalith. He was discharged home uneventfully and no symptoms was observed in 3 months follow-up.
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A previously healthy 39-year-old woman was hospitalized with upper abdominal pain for 1-month duration. A semipedunculated protrusion with smooth surface was found at the gastric angle measuring 2.0 × 2.5-cm by gastroscopy. Endoscopic ultrasound (EUS) showed a hypoechoic mass originated from the mucosal layer. Abdominal computed tomography (CT) revealed a circular pedunculated and slightly low-density mass with mild enhancement in the stomach cavity. Endoscopic submucosal dissection (ESD) was performed. Postoperative histopathology examination revealed the tumor was composed of proliferated spindle cells with eosinophil infiltration which were around small blood vessels and mucosal glands arranged in an "onion-skin" appearance. Immunohistochemical analysis of the spindle cells showed CD34 was positive and CD117, S100, DOG-1, SMA, Desmin were negative. The patient was diagnosed as gastric inflammatory fibroid polyp (IFP) and no symptoms was observed in 12 months follow-up.
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A previously healthy 56-year-old female was hospitalized with intermittent melena and transient syncope for 1-month duration. Physical examination on admission showed heart rate was 105 beats per minute and blood pressure was 89/55 mmHg. Her hemoglobin was 6.7 g/dl. She received fluid infusion, blood transfusion, acid suppression and hemostasis treatment. Abdominal enhanced computed tomography (CT) demonstrated a well-defined mass with uniform adipose density in the antrum measuring 4 × 5 cm. Gastroscopy revealed a giant submucosal tumor with superficial ulceration in anterior wall of the gastric antrum. Endoscopic ultrasound (EUS) showed a homogeneous, well-circumscribed, hyperechoic mass originated from the submucosa layer. Distal partial gastrectomy was performed. Postoperative histopathology examination of the resected specimen revealed the tumor was composed of closely arranged and uniformly shaped proliferative mature adipocytes, which located in the submucosa layer with superficial mucosal ulcer. The patient was diagnosed as giant gastric lipoma with superficial ulcer and no symptoms was observed in 3 months follow-up.
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Neoplasias Gástricas , Humanos , Feminino , Pessoa de Meia-Idade , Neoplasias Gástricas/complicações , Neoplasias Gástricas/diagnóstico por imagem , Neoplasias Gástricas/cirurgia , Úlcera/complicações , Hemorragia Gastrointestinal/diagnóstico por imagem , Hemorragia Gastrointestinal/etiologia , Hemorragia Gastrointestinal/cirurgia , Antro Pilórico , Gastrectomia/métodosRESUMO
PURPOSE: To methodically assess the effectiveness of augmentative plating (AP) and exchange nailing (EN) in managing nonunion following intramedullary nailing for long bone fractures of the lower extremity. METHODS: PubMed, EMBASE, Web of Science, and the Cochrane Library were searched to gather clinical studies regarding the use of AP and EN techniques in the treatment of nonunion following intramedullary nailing of lower extremity long bones. The search was conducted up until May 2023. The original studies underwent an independent assessment of their quality, a process conducted utilizing the Newcastle-Ottawa scale. Data were retrieved from these studies, and meta-analysis was executed utilizing Review Manager 5.3. RESULTS: This meta-analysis included 8 studies involving 661 participants, with 305 in the AP group and 356 in the EN group. The results of the meta-analysis demonstrated that the AP group exhibited a higher rate of union (odds ratio: 8.61, 95% confidence intervals (CI): 4.12 - 17.99, p < 0.001), shorter union time (standardized mean difference (SMD): -1.08, 95 % CI: -1.79 - -0.37, p = 0.003), reduced duration of the surgical procedure (SMD: -0.56, 95 % CI: -0.93 - -0.19, p = 0.003), less bleeding (SMD: -1.5, 95 % CI: -2.81 - -0.18), p = 0.03), and a lower incidence of complications (relative risk: -0.17, 95 % CI: -0.27 - -0.06, p = 0.001). In the subgroup analysis, the time for union in the AP group in nonisthmal and isthmal nonunion of lower extremity long bones was shorter compared to the EN group (nonisthmal SMD: -1.94, 95 % CI: -3.28 - -0.61, p < 0.001; isthmal SMD: -1.08, 95 % CI: -1.64 - -0.52, p = 0.002). CONCLUSION: In the treatment of nonunion in diaphyseal fractures of the long bones in the lower extremity, the AP approach is superior to EN, both intraoperatively (with reduced duration of the surgical procedure and diminished blood loss) and postoperatively (with an elevated union rate, shorter union time, and lower incidence of complications). Specifically, in the management of nonunion of lower extremity long bones with non-isthmal and isthmal intramedullary nails, AP demonstrated shorter union time in comparison to EN.
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ß-Branched chiral amines with contiguous stereocenters are valuable building blocks for preparing various biologically active molecules. However, their asymmetric synthesis remains challenging. Herein, we report a highly diastereo- and enantioselective biocatalytic approach for preparing a broad range of ß-branched chiral amines starting from their corresponding racemic ketones. This involves a dynamic kinetic resolution-asymmetric reductive amination process catalyzed using only an imine reductase. Four rounds of protein engineering endowed wild-type PocIRED with higher reactivity, better stereoselectivity, and a broader substrate scope. Using the engineered enzyme, various chiral amine products were synthesized with up to >99.9% ee, >99:1 dr, and >99% conversion. The practicability of the developed biocatalytic method was confirmed by producing a key intermediate of tofacitinib in 74% yield, >99.9% ee, and 98:2 dr at a challenging substrate loading of 110 g L-1. Our study provides a highly capable imine reductase and a protocol for developing an efficient biocatalytic dynamic kinetic resolution-asymmetric reductive amination reaction system.
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BACKGROUND: To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993-2021 were analyzed. METHODS: Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993-2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. RESULTS: With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020-2021 (average 0.5 per million). During 1993-2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. CONCLUSIONS: The evidence of low incidence during 2020-2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.
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Vírus do Sarampo , Sarampo , Humanos , Vírus do Sarampo/genética , Genótipo , Filogenia , China/epidemiologia , Sarampo/epidemiologia , Sarampo/prevenção & controleRESUMO
In this study, single Ni2 clusters (two Ni atoms bridged by a lattice oxygen) are successfully synthesized on monolayered CuO. They exhibit a remarkable activity toward low-temperature CO2 thermal dissociation, in contrast to cationic Ni atoms that nondissociatively adsorb CO2 and metallic Ni ones that are chemically inert for CO2 adsorption. Density functional theory calculations reveal that the Ni2 clusters can significantly alter the spatial symmetry of their unoccupied frontier orbitals to match the occupied counterpart of the CO2 molecule and enable its low-temperature dissociation. This study may help advance single-cluster catalysis and exploit the unexcavated mechanism for low-temperature CO2 activation.