A cuproptosis-related gene expression signature predicting clinical prognosis and immune responses in intrahepatic cholangiocarcinoma detected by single-cell RNA sequence analysis.

BACKGROUND: Cholangiocarcinoma represents a malignant neoplasm originating from the hepatobiliary tree, with a subset of tumors developing inside the liver. Intrahepatic cholangiocarcinomas (ICC) commonly exhibit an asymptomatic presentation, rendering both diagnosis and treatment challenging. Cuproptosis, an emerging regulated cell death pathway induced by copper ions, has garnered attention recently. As cancer cells show altered copper metabolism and comparatively higher copper needs, cuproptosis may play a role in the development of ICC. However, studies investigating this possibility are currently lacking. METHODS: Single-cell and bulk RNA sequence data were analyzed, and correlations were established between the expression of cuproptosis-related molecules and ICC patient survival. Genes with predicting survival were used to create a CUPT score using Cox and LASSO regression and tumor mutation burden (TMB) analysis. The CIBERSORT software was employed to characterize immune cell infiltration within the tumors. Furthermore, immune infiltration prediction, biological function enrichment, and drug sensitivity analyses were conducted to explore the potential implications of the cuproptosis-related signature. The effects of silencing solute carrier family 39 member 4 gene (SLC39A4) expression using siRNA were investigated using assays measuring cell proliferation, colony formation, and cell migration. Key genes of cuproptosis were detected by western blotting. RESULTS: The developed CUPT score divided patients into high and low CUPT score groups. Those with a low score had significantly better prognosis and longer survival. In contrast, high CUPT scores were associated with worse clinical outcomes and significantly higher TMB. Comparisons of the two groups also indicated differences in the immune infiltrate present in the tumors. Finally, we were able to identify 95 drugs potentially affecting the cuproptosis pathway. Some of these might be effective in the treatment of ICC. The in vitro experiments revealed that suppressing the expression of SLC39A4 in ICC cell lines resulted in reduced cell proliferation, colony formation, and cell migration. It also led to an increase in cell death and the upregulation of key genes associated with cuproptosis, namely ferredoxin 1 (FDX1) and dihydrolipoyl transacetylase (DLAT). These findings strongly suggest that this cuproptosis-associated molecule may play a pivotal role in the development and metastasis of ICC. CONCLUSIONS: Changes in the expression of a cuproptosis-related gene signature can predict the clinical prognosis of ICC with considerable accuracy. This supports the notion that cuproptosis influences the diversity and complexity of the immune microenvironment, mutational landscape, and biological behavior of ICC. Understanding this pathway better may hold promise for the development of innovative strategies in the management of this disease.

Retracted: Resveratrol Suppresses Human Nasopharyngeal Carcinoma Cell Growth Via Inhibiting Differentiation Antagonizing Non-Protein Coding RNA (DANCR) Expression.

The authors have requested retraction due to the identification of errors in the data. Reference: Jiafeng Zhang, Xiaojie Jin, Chuan Zhou, Hui Zhao, Ping He, Yalin Hao, Qiongna Dong. Resveratrol Suppresses Human Nasopharyngeal Carcinoma Cell Growth Via Inhibiting Differentiation Antagonizing Non-Protein Coding RNA (DANCR) Expression. Med Sci Monit, 2020; 26: e923622. DOI: 10.12659/MSM.923622.

Computational fluid dynamics-based design and in vitro characterization of a novel pediatric pump-lung.

BACKGROUND: Although extracorporeal membrane oxygenation (ECMO) has been used to provide temporary support for pediatric patients suffering severe respiratory or cardiac failure since 1970, ECMO systems specifically designed for pediatric patients, particularly for long-term use, remain an unmet clinical need. We sought to develop a new pediatric ECMO system, that is, pediatric pump-lung (PPL), consisting of a unique cylinder oxygenator with an outside-in radial flow path and a centrifugal pump. METHODS: Computational fluid dynamics was used to analyze the blood fluid field for optimized biocompatible and gas exchange performances in terms of flow characteristics, hemolysis, and gas transfer efficiency. Ovine blood was used for in vitro hemolysis and gas transfer testing. RESULTS: Both the computational and experimental data showed that the pressure drop through the PPL's oxygenator is significantly low, even at a flow rate of more than 3.5 L/min. The PPL showed better hemolysis performance than a commercial ECMO circuit consisting of the Quadrox-iD pediatric oxygenator and the Rotaflow pump at a 3.5 L/min flow rate and 250 mm Hg afterload pressure. The oxygen transfer rate of the PPL can reach over 200 mL/min at a flow rate of 3.5 L/min. CONCLUSIONS: The PPL has the potential to provide adequate blood pumping and excellent respiratory support with minimal risk of hemolysis for a wide range of pediatric patients.

Multiple-ion Management of Perovskites by Regulating Spatial Distribution of Hydroxyls in Oligosaccharides.

Suppressing migrations of intrinsic and extrinsic ions (e.g., Pb2+ , I- , FA+ /MA+ , and Li+ ) in organic-inorganic hybrid perovskites is critical for alleviating the hysteresis and degradation of perovskite solar cells (PSCs). However, various additives reported for that purpose usually interact with one or two types of those ions, not inhibiting multiple-ion migrations simultaneously. Two oligosaccharides (ß-cyclodextrin (ß-CD) and maltotetraose (G4)), containing 14 hydroxyls (-OH) with different spatial distributions, for the suppression of multiple-ion migrations in PSCs is herein employed. Compared to linear arrangement of -OH in G4, annular distribution of -OH around wide and narrow rims of ß-CD can form supramolecular multi-site interactions in a focal manner with various ions, more effectively capturing and immobilizing these migrated ions. With this multiple-ion management strategy, ß-CD-based PSCs exhibit an impressive efficiency of 24.22% with negligible hysteresis and excellent device stability. This work highlights the significances of multi-site interactions and molecular configuration of the additive for inhibiting multi-ion migrations in PSCs.

Identification and genomic characterization of a novel HIV-1 unique recombinant form (CRF01_AE/CRF07_BC) in Zhejiang Province, China.

Mutation and recombination are important mechanisms leading to the frequent evolution and genetic diversity of viruses as HIV-1. In this study, we identified the near full-length genomic characterization of a novel HIV-1 unique recombinant form (URF) strain (Sample ID: ZJ20202195/ZJ/CHN/2020, hereafter referred to as ZJ20202195) isolated during the HIV-1 molecular surveillance in 2020 in Zhejiang Province, China, through different recombination analysis tools and phylogenetic analysis. Our results amply proved that the near full-length genome (NFLG) sequence of ZJ20202195 was a novel HIV-1 unique recombinant form (URF) consisting of CRF01_AE and CRF07_BC subtype, and delimited three recombinant segments, of which the Segment I (HXB2:776-5559 nucleotide (nt)) and Segment III (HXB2:6224-9412 nt) were mainly originated from CRF01_AE cluster g4a strains prevalent in China and Segment II (HXB2:5560-6223 nt) was from CRF07_BC subtype. Overall, our findings provide insight and a scientific basis in the genetic diversity and accurate determination of HIV-1 recombinant strains in China.

Identification and relative contributions of environmental driving factors for abundant and rare bacterial taxa to thermal stratification evolution.

The thermal stratification of reservoir affects water quality, and water quality evolution is largely driven by microorganisms. However, few studies have been conducted on the response of abundant taxa (AT) and rare taxa (RT) to thermal stratification evolution in reservoirs. Here, using high-throughput absolute quantitative techniques, we examined the classification, phylogenetic diversity patterns, and assembly mechanisms of different subcommunities during different periods and investigated the key environmental factors driving community construction and composition. The results showed that community and phylogenic distances of RT were higher than AT (P < 0.001), and community and phylogenic distances of the different subcommunities were significantly positively correlated with the dissimilarity of environmental factors (P < 0.001). Nitrate (NO3--N) was the main driving factor of AT and RT in the water stratification period, and Mn was the main driving factor in the water mixing period (MP) based on redundancy analysis (RDA) and random forest analysis (RF). The interpretation rate of key environmental factors based on the selected indicator species in RT by RF was higher than that of AT, and Xylophilus (10.5%) and Prosthecobacter (0.1%) had the highest average absolute abundance in AT and RT during the water stable stratification period (SSP), whereas Unassigned had the highest abundance during the MP and weak stratification period (WSP). The network of RT and environmental factors was more stable than that of AT, and stratification made the network more complex. NO3--N was the main node of the network during the SSP, and manganese (Mn) was the main node during the MP. Dispersal limitation dominated community aggregation, the proportion of AT was higher than that of RT. Structural Equation Model (SEM) showed that NO3--N and temperature (T) had the highest direct and total effects on ß-diversity of AT and RT for the SP and MP, respectively.

Spatial and temporal dynamic response of abundant and rare aerobic denitrifying bacteria to dissolved organic matter in natural water: A case study of Lake Baiyangdian, China.

Revealing the responses of abundant and rare aerobic denitrifying bacteria to dissolved organic matter (DOM) composition is essential for understanding the aquatic N cycle ecosystems. In this study, fluorescence region integration and high-throughput sequencing techniques were used to investigate the spatiotemporal characteristics and dynamic response of DOM and aerobic denitrifying bacteria. The DOM compositions were significantly different among the four seasons (P < 0.001) without spatial differences. Tryptophan-like substances (P2, 27.89-42.67%) and microbial metabolites (P4, 14.62-42.03%) were the dominant components, and DOM exhibited strong autogenous characteristics. Abundant (AT), moderate (MT), and rare taxa (RT) of aerobic denitrifying bacteria showed significant and spatiotemporal differences (P < 0.05). The responses of α-diversity and niche breadth of AT and RT to DOM differed. The DOM explanation proportion for aerobic denitrifying bacteria exhibited spatiotemporal differences based on redundancy analysis. Foliate-like substances (P3) had the highest interpretation rate of AT in spring and summer, while humic-like substances (P5) had the highest interpretation rate of RT in spring and winter. Network analysis showed that RT networks were more complex than AT networks. Pseudomonas was the main genus associated with DOM in AT on a temporal scale, and was more strongly correlated with tyrosine-like substances (P1), P2, and P5. Aeromonas was the main genus associated with DOM in AT on a spatial scale and was more strongly correlated with P1 and P5. Magnetospirillum was the main genus associated with DOM in RT on a spatiotemporal scale, which was more sensitive to P3 and P4. Special operational taxonomic units were transformed between AT and RT with seasonal changes, but not between the two regions. To summarize, our results revealed that bacteria with different abundances utilized DOM components differently, and provides new insight on the spatiotemporal response of DOM and aerobic denitrifying bacteria in aquatic ecosystems of biogeochemical significance.

A diagnostic model based on color vision examination for dysthyroid optic neuropathy using Hardy-Rand-Rittler color plates.

PURPOSE: To investigate color vision deficiency and the value of Hardy-Rand-Rittler (HRR) color plates in monitoring dysthyroid optic neuropathy (DON) to improve the diagnosis of DON. METHODS: The participants were divided into DON and non-DON (mild and moderate-to-severe) groups. All the subjects underwent HRR color examination and comprehensive ophthalmic examinations. The random forest and decision tree models based on the HRR score were constructed by R software. The ROC curve and accuracy of different models in diagnosing DON were calculated and compared. RESULTS: Thirty DON patients (57 eyes) and sixty non-DON patients (120 eyes) were enrolled. The HRR score was lower in DON patients than in non-DON patients (12.1 ± 6.2 versus 18.7 ± 1.8, p < 0.001). The major color deficiency was red-green deficiency in DON using HRR test. The HRR score, CAS, RNFL, and AP100 were found to be important factors in predicting DON from random forest and selected by decision tree to construct the multifactor model. The sensitivity, specificity, and the area under the curve (AUC) of the HRR score were 86%, 72%, and 0.87, respectively. The HRR score decision tree had a sensitivity, specificity, and AUC of 93%, 57%, and 0.75, respectively, with an accuracy of 82%. The data of the multifactor decision tree were 90%, 89%, and 0.93 for sensitivity, specificity, and AUC, respectively, with an accuracy of 91%. CONCLUSION: The HRR test was valid as screening method for DON. The multifactor decision tree based on the HRR test improved the diagnostic efficacy for DON. An HRR score of less than 12 and red-green deficiency may be characteristic of DON.

Advanced inter-spacecraft offset frequency setting strategy for the Taiji program based on a two-stage optimization algorithm.

For space-based gravitational wave (GW) detection, the continuity of detection data acquisition is crucial to the inversion of wave sources and the realization of scientific goals. To control the inter-spacecraft beat-note frequency in an appropriate range for continuous gravitational wave detection and to reduce the upper bound of the beat-note frequency for improving the detection capability, a two-stage optimization algorithm is proposed to solve the offset frequency setting strategy in the Taiji program. The optimization objectives are the maximum offset frequency duration and minimum upper bound of the beat-note frequency. Considering all feasible phase-locked schemes, Doppler frequency shift, and the bandwidth of the phasemeter, a series of offset frequency setting strategies satisfying the conditions was obtained. The solution results show that the upper bound can be reduced to 16 MHz and, in this case, the offset frequency changes nine times with a minimum and maximum offset frequency duration of 90 days and 713 days, respectively. If the Doppler frequency shift is constrained, the minimum upper bound can be reduced to 14 MHz. When the minimum duration is increased, the minimum upper bound is increased. These results show that, by varying the offset frequency a limited number of times, the data continuity requirements of the Taiji program can be satisfied, and the phasemeter development difficulty and detection capability can be balanced, and may provide a reference for the phasemeter design, the setting of phase-locking schemes, and inter-spacecraft offset frequency in the Taiji program.

Hematological characteristics of COVID-19 patients with fever infected by the Omicron variant in Shanghai: A retrospective cohort study in China.

BACKGROUND: A wave of the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has rapidly spread in Shanghai, China. Hematological abnormalities have been reported in coronavirus disease 2019 (COVID-19) patients; however, the difference in hematological parameters between COVID-19 patients with fever and patients who are febrile from other causes remains unexplored. METHODS: This retrospective cohort study enrolled 663 SARS-CoV-2 positive patients identified by RT-PCR. Clinical parameters, including age, sex, and threshold cycle values of all COVID-19 patients, and hematological parameters of COVID-19 patients in the fever clinic were abstracted for analysis. RESULTS: Overall, 60.8% of COVID-19 patients were male, and the median age was 45 years. Most of COVID-19 patients were asymptomatic, while 25.8% of patients showed fever and 10.9% of patients had other emergencies. COVID-19 patients with fever had significantly lower white blood cells (WBCs), neutrophils, lymphocytes, platelets and C-reactive protein (CRP), and significantly higher monocyte-to-lymphocyte ratio (MLR), platelet-to-lymphocyte ratio (PLR), mean platelet volume (MPV), and mean platelet volume-to-platelet ratio (MPR) levels, compared with those in SARS-CoV-2 negative patients with fever from other causes (p < 0.05). Neutrophil-to-lymphocyte ratio (NLR), PLR, and systemic inflammatory index (SII) levels were significantly higher in COVID-19 patients with emergencies (p < 0.05). WBCs showed the best performance with an area under the curve (0.756), followed by neutrophils (0.730) and lymphocytes (0.694) in the diagnosis of COVID-19 in the fever clinic. CONCLUSION: WBCs, neutrophils, lymphocytes, platelets, CRP and MLR, PLR, and MPR may be useful in early diagnosis of COVID-19 in the fever clinic.

Spinal Cord Infarction With Prolonged Femoral Venoarterial Extracorporeal Membrane Oxygenation.

OBJECTIVES: There have been sporadic reports of ischemic spinal cord injury (SCI) during venoarterial extracorporeal membrane oxygenation (VA-ECMO) support. The authors observed a troubling pattern of this catastrophic complication and evaluated the potential mechanisms of SCI related to ECMO. DESIGN: This study was a case series. SETTING: This study was performed at a single institution in a University setting. PARTICIPANTS: Patients requiring prolonged VA-ECMO were included. INTERVENTIONS: No interventions were done. This was an observational study. MEASUREMENTS AND MAIN RESULTS: Four hypotheses of etiology were considered: (1) hypercoagulable state/thromboembolism, (2) regional hypoxia/hypocarbia, (3) hyperperfusion and spinal cord edema, and (4) mechanical coverage of spinal arteries. The SCI involved the lower thoracic (T7-T12 level) spinal cord to the cauda equina in all patients. Seven out of 132 (5.3%) patients with prolonged VA-ECMO support developed SCI. The median time from ECMO cannulation to SCI was 7 (range: 6-17) days.There was no evidence of embolic SCI or extended regional hypoxia or hypocarbia. A unilateral, internal iliac artery was covered by the arterial cannula in 6/7 86%) patients, but flow into the internal iliac was demonstrated on imaging in all available patients. The median total flow (ECMO + intrinsic cardiac output) was 8.5 L/min (LPM), and indexed flow was 4.1 LPM/m2. The median central venous oxygen saturation was 88%, and intracranial pressure was measured at 30 mmHg in one patient, suggestive of hyperperfusion and spinal cord edema. CONCLUSIONS: An SCI is a serious complication of extended peripheral VA-ECMO support. Its etiology remains uncertain, but the authors' preliminary data suggested that spinal cord edema from hyperperfusion or venous congestion could contribute.

Enhanced Detection Precision of the Taiji Program by Frequency Setting Strategy Based on a Hierarchical Optimization Algorithm.

For space-based gravitational wave detection, a laser interferometric measurement system composed of a three-spacecraft formation offers the most rewarding bandwidth of astrophysical sources. There are no oscillators available that are stable enough so that each spacecraft could use its own reference frequency. The conversion between reference frequencies and their distribution between all spacecrafts for the synchronization of the different metrology systems is the job of the inter-spacecraft frequency setting strategy, which is important for continuously acquiring scientific data and suppressing measurement noise. We propose a hierarchical optimization algorithm to solve the frequency setting strategy. The optimization objectives are minimum total readout displacement noise and maximum beat-note frequency feasible range. Multiple feasible parameter combinations were obtained for the Taiji program. These optimized parameters include lower and upper bounds of the beat note, sampling frequency, pilot tone signal frequency, ultrastable clock frequencies, and modulation depth. Among the 20 Pareto optimal solutions, the minimum total readout displacement noise was 4.12 pm/Hz, and the maximum feasible beat-note frequency range was 23 MHz. By adjusting the upper bound of beat-note frequency and laser power transmitted by the telescope, we explored the effects of these parameters on the minimum total readout displacement noise and optimal local laser power in greater depth. Our results may serve as a reference for the optimal design of laser interferometry system instrument parameters and may ultimately improve the detection performance and continuous detection time of the Taiji program.

Hue Recognition Competitive Fluorescent Lateral Flow Immunoassay for Aflatoxin M1 Detection with Improved Visual and Quantitative Performance.

Immunological detection of small molecules in a point-of-care (POC) format is of great significance yet remains challenging for accurate visual discrimination and quantitative analysis. Here, we report a novel hue recognition competitive fluorescent lateral flow immunoassay (HCLFIA) strip that allows both visual and quantitative detection of aflatoxin M1 (AFM1). The HCLFIA strip works on the basis of the ratiometric change of emission, arising from the overlap of fluorescence signals of two nanocomposites tagged with probe antibodies and coated antigens. A visually discernible orange-red-to-green fluorescence color change allows the naked eye semiquantitative readout of AFM1 around the threshold concentration (0.05 ng mL-1), yielding a visible detection limit of 0.02 ng mL-1. Moreover, using a custom smartphone-based device and color chart analysis, ultrasensitive quantitative detection of AFM1 can be achieved with a low limit of detection at 0.0012 ng mL-1, which is considerably better than those of the previously reported colorimetric and fluorescent strips. The accuracy performed in spiked milk samples ranged from 97.91 to 113.12% with a coefficient of variation below 7.8%, showing good consistency with the results from isotope dilution liquid chromatography-tandem mass spectrometry. Thanks to the unique hue recognition scheme, the HCLFIA strip holds great potential for POC detection of small molecules.

Neutrophil dysfunction due to continuous mechanical shear exposure in mechanically assisted circulation in vitro.

OBJECTIVE: Leukocytes play an important role in the body's immune system. The aim of this study was to assess alterations in neutrophil phenotype and function in pump-assisted circulation in vitro. METHODS: Human blood was circulated for four hours in three circulatory flow loops with a CentriMag blood pump operated at a flow of 4.5 L/min at three rotational speeds (2100, 2800, and 4000 rpm), against three pressure heads (75, 150, and 350 mm Hg), respectively. Blood samples were collected hourly for analyses of neutrophil activation state (Mac-1, CD62L, CD162), neutrophil reactive oxygen species (ROS) production, apoptosis, and neutrophil phagocytosis. RESULTS: Activated neutrophils indicated by both Mac-1 expression and decreased surface expression of CD62L and CD162 receptors increased with time in three loops. The highest level of neutrophil activation was observed in the loop with the highest rotational speed. Platelet-neutrophil aggregates (PNAs) progressively increased in two loops with lower rotational speeds. PNAs peaked at one hour after circulation and decreased subsequently in the loop with the highest rotational speed. Neutrophil ROS production dramatically increased at one hour after circulation and decreased subsequently in all three loops with similar levels and trends. Apoptotic neutrophils increased with time in all three loops. Neutrophil phagocytosis capacity in three loops initially elevated at one hour after circulation and decreased subsequently. Apoptosis and altered phagocytosis were dependent on rotational speed. CONCLUSIONS: Our study revealed that the pump-assisted circulation induced neutrophil activation, apoptosis, and functional impairment. The alterations were strongly associated with pump operating condition and duration.

Inter-spacecraft offset frequency setting strategy in the Taiji program.

For controlling the beat frequency of heterodyne interferometry so that the Taiji program can detect gravitational waves in space, an offset frequency setting strategy based on a linear programming algorithm is proposed. Considering factors such as Doppler frequency shift, phase-locking scheme, laser relative intensity noise, and phase detector bandwidth, inter-spacecraft offset frequency setting results suitable for the Taiji program are obtained. During the six years of running the detection process, the use of frequency bounds in the range of [5 MHz, 25 MHz] showed that offset frequencies will remain unchanged for a maximum of 1931 days. If the upper and lower bounds are adjusted, and the relative motion between spacecraft is further constrained, the offset frequencies do not need to change during the time of the mission. These results may provide insights into selecting the phase detector and designing operation parameters such as orbit and laser modulation frequency in the Taiji program.

Research advances of N6-methyladenosine in diagnosis and therapy of pancreatic cancer.

BACKGROUND: N6-methyladenosine (m6A) is the addition of a methyl group on the N6 position of adenosine and is the most prevalent and abundant epigenetic modification in eukaryote mRNA. m6A marks are added to mRNA by the m6A methyltransferase complex ("writers"), removed by m6A demethylases ("erasers"), and recognized by m6A-binding proteins ("readers"). Recent evidence has shown that the m6A modification plays a crucial role in the pathogenic mechanism and malignant progression of pancreatic cancer, with roles in cell survival, proliferation, migration, invasion, tumor metastasis, and drug resistance. METHODS: Literature was searched in Pubmed and Web of Science for the following keywords: "N6-methyladenosine", "pancreatic cancer", "epigenetic modification", "immunotherapy". RESULTS: Among classical m6A regulators, while METTL3, METTL14, WTAP, FTO, YTHDF2, IGF2BP1-3, hnRNPC, and NKAP are upregulated in pancreatic cancer, METTL16 and ALKBH5 are downregulated in pancreatic cancer. m6A modification has been investigated in pancreatic cancer therapy. CONCLUSION: Dysregulated m6A and its related factors in pancreatic cancer cells and patients indicate their potential values as novel biomarkers in pancreatic cancer diagnosis and targeted therapy.

Models of Shear-Induced Platelet Activation and Numerical Implementation With Computational Fluid Dynamics Approaches.

Shear-induced platelet activation is one of the critical outcomes when blood is exposed to elevated shear stress. Excessively activated platelets in the circulation can lead to thrombus formation and platelet consumption, resulting in serious adverse events such as thromboembolism and bleeding. While experimental observations reveal that it is related to the shear stress level and exposure time, the underlying mechanism of shear-induced platelet activation is not fully understood. Various models have been proposed to relate shear stress levels to platelet activation, yet most are modified from the empirically calibrated power-law model. Newly developed multiscale platelet models are tested as a promising approach to capture a single platelet's dynamic shape during activation, but it would be computationally expensive to employ it for a large-scale analysis. This paper summarizes the current numerical models used to study the shear-induced platelet activation and their computational applications in the risk assessment of a particular flow pattern and clot formation prediction.

Deeper Insight into the Role of Organic Ammonium Cations in Reducing Surface Defects of the Perovskite Film.

Organic ammonium salts (OASs) have been widely used to passivate perovskite defects. The passivation mechanism is usually attributed to coordination of OASs with unpaired lead or halide ions, yet ignoring their interaction with excess PbI2 on the perovskite film. Herein, we demonstrate that OASs not only passivate defects by themselves, but also redistribute excess aggregated PbI2 into a discontinuous layer, augmenting its passivation effect. Moreover, alkyl OAS is more powerful to disperse PbI2 than a F-containing one, leading to better passivation and device efficiency because F atoms restrict the intercalation of OAS into PbI2 layers. Inspired by this mechanism, exfoliated PbI2 nanosheets are adopted to provide better dispersity of PbI2 , further boosting the efficiency to 23.14 %. Our finding offers a distinctive understanding of the role of OASs in reducing perovskite defects, and a route to choosing an OAS passivator by considering substitution effects rather than by trial and error.

Phylogenetic evidence of HIV-1 transmission linkage between two men who have sex with men.

BACKGROUND: In China, an HIV-infected man (complainant; P2) alleged that another man (defendant; P1) had unlawfully infected him with HIV through unprotected homosexual contact in 2018. METHODS: We employed epidemiological, serological and phylogenetic analyses to investigate the transmission linkage between two men who have sex with men (MSM). Partial segments of three HIV-1 gene regions (gag, pol, and env) were amplified and sequenced by cloning. Maximum-likelihood (ML) and Bayesian methods were used to determine the direction and estimate the timing of transmission. Local control sequences and database control sequences were also used in the phylogenetic analysis. RESULTS: It indicated that P2 underwent HIV seroconversion after P1 was diagnosed as HIV positive. The time to the most recent common ancestor (tMRCA) estimates consistently showed that P1 most likely became HIV-1 infected at an earlier date than P2. P1 and P2 were infected with the same HIV-1 CRF01_AE subtype according to segments of all three gene regions (gag, pol, and env). All three genetic regions of P1 have been subject to more potential selective forces than those of P2, indicating a longer evolutionary history. Bayesian and ML trees showed similar paraphyletic-monophyletic topologies of gag and env, with the virus from P1 located at the root, which supported a P1-to-P2 transmission direction. CONCLUSIONS: Phylogenetic investigations can elucidate HIV transmission linkage and might empower its use in the opposition of the intentional transmission of HIV-1 as a forensic tool.

Design, green synthesis, antioxidant activity screening, and evaluation of protective effect on cerebral ischemia reperfusion injury of novel monoenone monocarbonyl curcumin analogs.

Antioxidants with high efficacy and low toxicity have the potential to treat cerebral ischemia reperfusion injury (CIRI). Dienone monocarbonyl curcumin analogs (DMCA) capable of overcoming the instability and pharmacokinetic defects of curcumin possess notable antioxidant activity but are found to be significantly toxic. In this study, a novel skeleton of the monoenone monocarbonyl curcumin analogue sAc possessing reduced toxicity and improved stability was designed on the basis of the DMCA skeleton. Moreover, 32 sAc analogs were obtained by applying a green, simple, and economical synthetic method. Multiple sAc analogs with an antioxidant protective effect in PC12 cells were screened using an H2O2-induced oxidative stress damage model, and quantitative evaluation of structure-activity relationship (QSAR) model with regression coefficient of R2 = 0.918921 was built through random forest algorithm (RF). Among these compounds, the optimally active compound sAc15 elicited a potent protective effect on cell growth of PC12 cells by effectively eliminating ROS generation in response to oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway. In addition, sAc15 exhibited good protection against CIRI in the mice middle cerebral artery occlusion (MCAO) model. In this paper, we provide a novel class of antioxidants and a potential compound for stroke treatment.