Engineering an Organic Nanoplatform for Augmented Pyroeletroimmunotherapy.

Photothermal immunotherapy has shown great promise in the treatment of tumor metastasis. However, the thermal resistance of tumor cells substantially compromises the treatment effect of photothermal immunotherapy. Herein, a high-performance organic pyroelectric nanoplatform, tBu-TPAD-BF2 nanoparticles (NPs), is rationally engineered for the effective pyroelectroimmunotherapy of tumor metastasis. Biocompatible tBu-TPAD-BF2 NPs with excellent pyroelectric and photothermal conversion properties are constructed by assembling organic, low-bandgap pyroelectric molecules with amphiphilic polymers. After internalization by tumor cells, treatment with tBu-TPAD-BF2 NPs causes an apparent temperature elevation upon near-infrared (NIR) laser irradiation, inducing potent immunogenic cell death (ICD). Additionally, the temperature variations under alternating NIR laser irradiation facilitate reactive oxygen species production for pyroelectric therapy, thus promoting ICD activation and lowering thermal resistance. Importantly, in vivo assessments illustrate that tBu-TPAD-BF2 NPs in combination with NIR laser exposure notably inhibit primary and distant tumor proliferation and prominently retarded lung metastasis. RNA profiling reveals that treatment with tBu-TPAD-BF2 NPs markedly suppresses metastasis under NIR laser illumination by downregulating metastasis-related genes and upregulating immune response-associated pathways. Therefore, this study provides a strategy for designing high-performance pyroelectric nanoplatforms to effectively cure tumor metastasis, thereby overcoming the inherent shortcomings of photothermal immunotherapy.

The emergence and circulation of human immunodeficiency virus (HIV)-1 subtype C.

Introduction. Human immunodeficiency virus (HIV)-1 subtype C is the most prevalent globally and is thought to have originated in non-human primates in the Democratic Republic of Congo.Hypothesis/Gap Statement. Although the global dominance of HIV-1 subtype C is well established, a thorough understanding of its evolutionary history and transmission dynamics across various risk populations remains elusive. The current knowledge is insufficient to fully capture the global diversification and dissemination of this subtype.Aim. We for the first time sought to investigate the global evolutionary history and spatiotemporal dynamics of HIV-1 subtype C using a selection of maximum-likelihood-based phylodynamic approaches on a total of 1210 near full-length genomic sequences sampled from 32 countries, collected in 4 continents, with sampling dates between 1986-2019 among various risk groups were analysed.Methodology. We subsampled the HIV-1 subtype C genomic datasets based on continent and risk group traits, and performed nucleotide substitution model selection analysis, maximum likelihood (ML) phylogenetic reconstruction, phylogenetic tree topology similarity analysis, temporal signal analysis and traced the timings of viral spread both geographically and by risk group.Results. Based on the phylodynamic analyses of four datasets (full1210, locrisk626, loc562 and risk393), we inferred the time to the most recent common ancestor (TMRCA) in the 1930s and an evolutionary rate of 0.0023 substitutions per site per year. The total number of introduction events of HIV-1 subtype C between continents and between risk groups is estimated to be 71 and 115, respectively. The largest number of introductions occurred from Africa to Europe (n=32), from not-recorded to heterosexual (n=40) and from heterosexual to not-recorded (n=51) risk groups.Conclusion. Our results emphasize that HIV subtype C has mainly spread from Africa to Europe, likely through heterosexual transmission.

Enantioselective synthesis of spiro-N,O-ketals via iridium and Brønsted acid co-catalyzed asymmetric formal [4+2] cycloaddition.

We present an iridium and Brønsted acid co-catalyzed enantioselective formal [4+2] cycloaddition reaction of cyclic enamides with 2-(1-hydroxyallyl)phenols. This method yields a wide range of N-unsubstituted spiro-N,O-ketals, with good efficiency (up to 94%) and excellent enantioselectivities (most >95% ee). The protocol features easy scale-up and facile product derivatization.

Optimizing ancestral trait reconstruction of large HIV Subtype C datasets through multiple-trait subsampling.

Large datasets along with sampling bias represent a challenge for phylodynamic reconstructions, particularly when the study data are obtained from various heterogeneous sources and/or through convenience sampling. In this study, we evaluate the presence of unbalanced sampled distribution by collection date, location, and risk group of human immunodeficiency virus Type 1 Subtype C using a comprehensive subsampling strategy and assess their impact on the reconstruction of the viral spatial and risk group dynamics using phylogenetic comparative methods. Our study shows that a most suitable dataset for ancestral trait reconstruction can be obtained through subsampling by all available traits, particularly using multigene datasets. We also demonstrate that sampling bias is inflated when considerable information for a given trait is unavailable or of poor quality, as we observed for the trait risk group. In conclusion, we suggest that, even if traits are not well recorded, including them deliberately optimizes the representativeness of the original dataset rather than completely excluding them. Therefore, we advise the inclusion of as many traits as possible with the aid of subsampling approaches in order to optimize the dataset for phylodynamic analysis while reducing the computational burden. This will benefit research communities investigating the evolutionary and spatio-temporal patterns of infectious diseases.

Formal (4+2) cycloaddition of azoalkenes with trifluoromethylimidoyl sulfoxonium ylides: synthesis of trifluoromethyl pyridazine derivatives.

CF3-substituted imidoyl sulfoxonium ylides (TFISYs) are extraordinarily versatile and powerful synthons for use in cyclization chemistry that affords diverse CF3-substituted N-heterocycles. We first reacted TFISYs as a two-atom synthon with readily available azoalkenes and then subjected the products to metal-free formal (4+2) cycloaddition chemistry. This protocol features mild conditions and broad substrate scope, is simple to operate, and provides highly functionalized trifluoromethylpyridazines that are widely found in bioactive molecules.

Fall Direction Detection in Motion State Based on the FMCW Radar.

Accurately detecting falls and providing clear directions for the fall can greatly assist medical staff in promptly developing rescue plans and reducing secondary injuries during transportation to the hospital. In order to facilitate portability and protect people's privacy, this paper presents a novel method for detecting fall direction during motion using the FMCW radar. We analyze the fall direction in motion based on the correlation between different motion states. The range-time (RT) features and Doppler-time (DT) features of the person from the motion state to the fallen state were obtained by using the FMCW radar. We analyzed the different features of the two states and used a two-branch convolutional neural network (CNN) to detect the falling direction of the person. In order to improve the reliability of the model, this paper presents a pattern feature extraction (PFE) algorithm that effectively eliminates noise and outliers in RT maps and DT maps. The experimental results show that the method proposed in this paper has an identification accuracy of 96.27% for different falling directions, which can accurately identify the falling direction and improve the efficiency of rescue.

Emotion Recognition Using Different Sensors, Emotion Models, Methods and Datasets: A Comprehensive Review.

In recent years, the rapid development of sensors and information technology has made it possible for machines to recognize and analyze human emotions. Emotion recognition is an important research direction in various fields. Human emotions have many manifestations. Therefore, emotion recognition can be realized by analyzing facial expressions, speech, behavior, or physiological signals. These signals are collected by different sensors. Correct recognition of human emotions can promote the development of affective computing. Most existing emotion recognition surveys only focus on a single sensor. Therefore, it is more important to compare different sensors or unimodality and multimodality. In this survey, we collect and review more than 200 papers on emotion recognition by literature research methods. We categorize these papers according to different innovations. These articles mainly focus on the methods and datasets used for emotion recognition with different sensors. This survey also provides application examples and developments in emotion recognition. Furthermore, this survey compares the advantages and disadvantages of different sensors for emotion recognition. The proposed survey can help researchers gain a better understanding of existing emotion recognition systems, thus facilitating the selection of suitable sensors, algorithms, and datasets.

Rhodium-Catalyzed 1,4-Aryl Rearrangement of Sulfur Ylide for the Synthesis of 2-Pyridyl Thioethers.

We report a novel rhodium-catalyzed rearrangement involving N-substituted 2-thiopyridones and diazoesters. This reaction proceeds through the rhodium-catalyzed formation of sulfur ylides, followed by a direct C-N bond cleavage to achieve N-to-C 1,4-pyridyl migration. The protocol can be used to construct various thiopyridines possessing tetrasubstituted carbon stereocenters in moderate to excellent yields, which expands the transformation pattern of sulfur ylide intermediates in rearrangement reactions.

Tracing the origin of an imported HIV-1 sub-subtype A6 strain first identified in Zhejiang Province, China.

Human migration and mobility have been identified as key drivers of HIV dissemination among nations, which increases the problem of genetic diversity. Here, we report the near full-length genome of HIV-1 A6 identified in a female patient in the remote mountain area of Lishui, Zhejiang Province, which is the first time A6 has been reported in China. The near full-length genome was amplified with two large amplicons of 5.5 kb and 3.7 kb, and then target PCR products were sequenced by Sanger sequencing. The A6 strain was confirmed by the Basic Local Alignment Search Tool (BLAST) and a maximum-likelihood (ML) phylogenetic tree. The time to the most recent common ancestor (tMRCA) was inferred to be 2004 (95% HPD interval: 2003-2006). The sequence harbored the L74I mutation, which is a key characteristic genetic marker of A6. Combining the above evidence with epidemiological investigations, this A6 strain was determined to be from Ukraine, which was supported by phylogenetic analysis. This study identified a foreign imported strain, indicating a trend of increasing complication in the HIV-1 epidemic in Zhejiang, China.

Highly Efficient and para-Selective C-H Functionalization of Polystyrene Providing a Versatile Platform for Diverse Applications.

Postpolymerization modification of polystyrene (PS) can afford numerous value-added materials with different functions and applications, but it has been hampered by the lack of efficient methods. We report herein a highly efficient and para-selective conversion of the C-H bonds of the aromatic ring of PS into diverse functional groups using a combination of thianthrenation and thio-Suzuki-Miyaura coupling reaction. Notably, the thianthrenation efficiency of PS is as high as 99% and the degree of thianthrenation can be conveniently controlled using stoichiometric tuning of the amount of thianthrene-S-oxide added, resulting in 24-99 mol % thianthrenation. In the subsequent thio-Suzuki-Miyaura coupling reaction, 18 functionalized PS containing various functional groups (-CH2OH, -OMe, -SMe, -OTBS, -CH3, -NHBoc, -OCOMe, -CHO, -COMe, -Si(Me)3, etc.) were successfully prepared with a high degree of functionalization (64-99 mol %). The obtained functionalized PS can be readily converted into diverse functional materials, including solid-phase synthesis resins, aggregation-induced emission fluorophores, as well as ionomer binders and ion-exchange membranes for energy conversion devices. This method imparts diverse functionality onto PS with extremely high efficiency and selectivity, providing a versatile platform to transform existing commodity PS plastics into high-performance materials.

Continuous epitaxy of single-crystal graphite films by isothermal carbon diffusion through nickel.

Multilayer van der Waals (vdW) film materials have attracted extensive interest from the perspective of both fundamental research1-3 and technology4-7. However, the synthesis of large, thick, single-crystal vdW materials remains a great challenge because the lack of out-of-plane chemical bonds weakens the epitaxial relationship between neighbouring layers8-31. Here we report the continuous epitaxial growth of single-crystal graphite films with thickness up to 100,000 layers on high-index, single-crystal nickel (Ni) foils. Our epitaxial graphite films demonstrate high single crystallinity, including an ultra-flat surface, centimetre-size single-crystal domains and a perfect AB-stacking structure. The exfoliated graphene shows excellent physical properties, such as a high thermal conductivity of ~2,880 W m-1 K-1, intrinsic Young's modulus of ~1.0 TPa and low doping density of ~2.2 × 1010 cm-2. The growth of each single-crystal graphene layer is realized by step edge-guided epitaxy on a high-index Ni surface, and continuous growth is enabled by the isothermal dissolution-diffusion-precipitation of carbon atoms driven by a chemical potential gradient between the two Ni surfaces. The isothermal growth enables the layers to grow at optimal conditions, without stacking disorders or stress gradients in the final graphite. Our findings provide a facile and scalable avenue for the synthesis of high-quality, thick vdW films for various applications.

Self-Assembled Aza-Boron-Dipyrromethene for Ferroptosis-Boosted Sonodynamic Therapy.

The presence of apoptosis inhibition proteins renders the cancer cells resistant to apoptosis, severely compromising the antitumor efficacy of sonodynamic therapy (SDT). Here, an intelligent anticancer nanoplatform based on an Aza-boron-dipyrromethene dye (denoted as Aza-BDY) is elaborately established for ferroptosis augmented SDT through cysteine (Cys) starvation. After endocytosis by tumor cells, Aza-BDY serves as both a ferroptosis inducing agent and a sonosensitizer for tumor treatment. The specific Cys response facilitates the disruption of redox homeostasis and initiation of cellular ferroptosis. Meanwhile, the released sonosensitizer causes efficient SDT and augments ferroptosis under ultrasound irradiation. Detailed in vitro and in vivo investigations demonstrate that the synergistic effect of Cys depletion and singlet oxygen (1 O2 ) generation significantly induces cancer-cell death and suppresses tumor proliferation with a high inhibition rate of 97.5 %.

The emergence and transmission dynamics of HIV-1 CRF07_BC in Mainland China.

A total of 1155 partial pol gene sequences of human immunodeficiency virus (HIV)-1 CRF07_BC were sampled between 1997 and 2015, spanning 13 provinces in Mainland China and risk groups [heterosexual, injecting drug users (IDU), and men who have sex with men (MSM)] to investigate the evolution, adaptation, spatiotemporal and risk group dynamics, migration patterns, and protein structure of HIV-1 CRF07_BC. Due to the unequal distribution of sequences across time, location, and risk group in the complete dataset ('full1155'), subsampling methods were used. Maximum-likelihood and Bayesian phylogenetic analysis as well as discrete trait analysis of geographical location and risk group were carried out. To study mutations of a cluster of HIV-1 CRF07_BC (CRF07-1), we performed a comparative analysis of this cluster to the other CRF07_BC sequences ('backbone_295') and mapped the mutations observed in the respective protein structure. Our findings showed that HIV-1 CRF07_BC most likely originated among IDU in Yunnan Province between October 1992 to July 1993 [95 per cent hightest posterior density (HPD): May 1989-August 1995] and that IDU in Yunnan Province and MSM in Guangdong Province likely served as the viral sources during the early and more recent spread in Mainland China. We also revealed that HIV-1 CRF07-1 has been spreading for roughly 20 years and continues to cause local transmission in Mainland China and worldwide. Overall, our study sheds light on the dynamics of HIV-1 CRF07_BC distribution patterns in Mainland China. Our research may also be useful in formulating public health policies aimed at controlling acquired immune deficiency syndrome in Mainland China and globally.

Concerns on the multiple nomenclature systems for SARS-CoV-2.

The multiple nomenclature systems of SARS-CoV-2 are confusing and have several issues. The emergence of variants of concern and variants of interest has posed an increased risk to global health. To assist with public discussion and communication with nonscientific audiences about significant mutations, and ultimately to inform the ongoing response to the COVID-19 pandemic, we scientists need to develop easy-to-pronounce and nonstigmatizing labels for significant mutations.

Lattice Polarity Manipulation of Quasi-vdW Epitaxial GaN Films on Graphene Through Interface Atomic Configuration.

Quasi van der Waals epitaxy, a pioneering epitaxy of sp3 -hybridized semiconductor films on sp2 -hybridized 2D materials, provides a way, in principle, to achieve single-crystal epilayers with preferred atom configurations that are free of substrate. Unfortunately, this has not been experimentally confirmed in the case of the hexagonal semiconductor III-nitride epilayer until now. Here, it is reported that the epitaxy of gallium nitride (GaN) on graphene can tune the atom arrangement (lattice polarity) through manipulation of the interface atomic configuration, where GaN films with gallium and nitrogen polarity are achieved by forming CONGa(3) or COGaN(3) configurations, respectively, on artificial CO surface dangling bonds by atomic oxygen pre-irradiation on trilayer graphene. Furthermore, an aluminum nitride buffer/interlayer leads to unique metal polarity due to the formation of an AlON thin layer in a growth environment containing trace amounts of oxygen, which explains the open question of why those reported wurtzite III-nitride films on 2D materials always exhibit metal polarity. The reported atomic modulation through interface manipulation provides an effective model for hexagonal nitride semiconductor layers grown on graphene, which definitely promotes the development of novel semiconductor devices.

Omicron: Call for updated vaccines.

The Omicron SARS-CoV-2 variant was potentially generated from a chronically infected COVID-19 patient vaccinated with an messenger RNA (mRNA)- or non-mRNA-based vaccine, offering the opportunity for the virus to evolve and mutate to evade the body's immune response. To understand the significance of this SARS-CoV-2 variant and what it means for the global response to the pandemic, vaccinologists should systematically evaluate the role of mRNA- and non-mRNA-based vaccines in the generation of novel SARS-CoV-2 variants, including variants of concerns (VOCs) and interest (VOIs), that occur via breakthrough vaccine-elicited immunity. Although COVID vaccine boosters are likely to offer some protection and mRNA- or non-mRNA-based vaccines can be adapted to new variants, such as Omicron, the requirement of a booster so soon after full vaccination, with further shots potentially required, is of concern given the impacts on human health. Therefore, in the race to protect the global population against novel SARS-CoV-2 VOCs and VOIs, there is an urgent need to create much more effective one-dose vaccines that can protect people over their entire lifetime.

Organocatalytic asymmetric formal oxidative coupling for the construction of all-aryl quaternary stereocenters.

A new catalytic asymmetric formal cross dehydrogenative coupling process for the construction of all-aryl quaternary stereocenters is disclosed, which provides access to rarely explored chiral tetraarylmethanes with excellent enantioselectivity. The suitable oxidation conditions and the hydrogen-bond-based organocatalysis have enabled efficient intermolecular C-C bond formation in an overwhelmingly crowded environment under mild conditions. para-Quinone methides bearing an ortho-directing group serve as the key intermediate. The precise loading of DDQ is critical to the high enantioselectivity. The chiral products have also been demonstrated as promising antiviral agents.