查看更多>>摘要：Immune evasion is a pivotal force shaping the evolution of viruses.Nonetheless,the extent to which virus evolution varies among populations with diverse immune backgrounds remains an unsolved mystery.Prior to the widespread SARS-CoV-2 infections in December 2022 and January 2023,the Chinese population possessed a markedly distinct(less potent)immune background due to its low infection rate,compared to countries experiencing multiple infection waves,presenting an unprecedented opportunity to investigate how the virus has evolved under different immune contexts.We compared the mutation spectrum and functional potential of the newly derived mutations that occurred in BA.5.2.48,BF.7.14 and BA.5.2.49-variants prevalent in China-with their counterparts in other countries.We found that the emerging mutations in the receptor-binding-domain region in these lineages were more widely dispersed and evenly distributed across different epitopes.These mutations led to a higher angiotensin-converting enzyme 2(ACE2)binding affinity and reduced potential for immune evasion compared to their counterparts in other countries.These findings suggest a milder immune pressure and less evident immune imprinting within the Chinese population.Despite the emergence of numerous immune-evading variants in China,none of them outcompeted the original strain until the arrival of the XBB variant,which had stronger immune evasion and subsequently outcompeted all circulating variants.Our findings demonstrated that the continuously changing immune background led to varying evolutionary pressures on SARS-CoV-2.Thus,in addition to viral genome surveillance,immune background surveillance is also imperative for predicting forthcoming mutations and understanding how these variants spread in the population.
查看更多>>摘要：Endogenous opioid antinociception is a self-regulatory mechanism that reduces chronic pain,but its underlying circuit mechanism remains largely unknown.Here,we showed that endogenous opioid antinociception required the activation of mu-opioid receptors(MORs)in GABAergic neurons of the central amygdala nucleus(CEA)in a persistent-hyperalgesia mouse model.Pharmacogenetic suppression of these CEAMOR neurons,which mimics the effect of MOR activation,alleviated the persistent hyperalgesia.Furthermore,single-neuron projection analysis revealed multiple projectome-based subtypes of CEAMOR neurons,each innervating distinct target brain regions.We found that the suppression of axon branches projecting to the parabrachial nucleus(PB)of one subtype of CEAMOR neurons alleviated persistent hyperalgesia,indicating a subtype-and axonal-branch-specific mechanism of action.Further electrophysiological analysis revealed that suppression of a distinct CEA-PB disinhibitory circuit controlled endogenous opioid antinociception.Thus,this study identified the central neural circuit that underlies endogenous opioid antinociception,providing new insight into the endogenous pain modulatory mechanisms.
查看更多>>摘要：More than 1000 years,the Meiyu-Baiu have shaped the uniqueness of natural resources,civilization and culture in the Yangtze River Basin of China and the main islands of Japan.In recent decades,frequent rainstorms and droughts have seemingly diminished the misty features of traditional Meiyu-Baiu rainfall.However,there is still no consensus on whether their traditional nature is suspended.In this study,we quantitatively demonstrate that the Meiyu-Baiu almost completely lost their traditional features during 1961-2023,～80％of which can be attributed to anthropogenic warming.Furthermore,in a warmer future,the traditional Meiyu-Baiu will be more unlikely to appear.This study underscores the urgency in adapting to climate shift because destructive extremes are measurably taking the place of mild and maternal rains.
查看更多>>摘要：We present EPR-Net,a novel and effective deep learning approach that tackles a crucial challenge in biophysics:constructing potential landscapes for high-dimensional non-equilibrium steady-state systems.EPR-Net leverages a nice mathematical fact that the desired negative potential gradient is simply the orthogonal projection of the driving force of the underlying dynamics in a weighted inner-product space.Remarkably,our loss function has an intimate connection with the steady entropy production rate(EPR),enabling simultaneous landscape construction and EPR estimation.We introduce an enhanced learning strategy for systems with small noise,and extend our framework to include dimensionality reduction and the state-dependent diffusion coefficient case in a unified fashion.Comparative evaluations on benchmark problems demonstrate the superior accuracy,effectiveness and robustness of EPR-Net compared to existing methods.We apply our approach to challenging biophysical problems,such as an eight-dimensional(8D)limit cycle and a 52D multi-stability problem,which provide accurate solutions and interesting insights on constructed landscapes.With its versatility and power,EPR-Net offers a promising solution for diverse landscape construction problems in biophysics.
Fang ZhouLinyuan LüJianguo LiuManuel Sebastian Mariani...
142-151页
查看更多>>摘要：Understanding the heterogeneous role of individuals in large-scale information spreading is essential to manage online behavior as well as its potential offline consequences.To this end,most existing studies from diverse research domains focus on the disproportionate role played by highly connected'hub'individuals.However,we demonstrate here that information superspreaders in online social media are best understood and predicted by simultaneously considering two individual-level behavioral traits:influence and susceptibility.Specifically,we derive a nonlinear network-based algorithm to quantify individuals'influence and susceptibility from multiple spreading event data.By applying the algorithm to large-scale data from Twitter and Weibo,we demonstrate that individuals'estimated influence and susceptibility scores enable predictions of future superspreaders above and beyond network centrality,and reveal new insights into the network positions of the superspreaders.
查看更多>>摘要：Despite the discovery of a series of fullerenes and a handful of noncarbon clusters with the typical topology of Ih-C60,the smallest fullerene with a large degree of curvature,C20,and its other-element counterparts are difficult to isolate experimentally.In coinage metal nanoclusters(NCs),the first all-gold fullerene,Au32,was discovered after a long-lasting pursuit,but the isolation of similar silvery fullerene structures is still challenging.Herein,we report a flying saucer-shaped 102-nuclei silver NC(Ag102)with a silvery fullerene kernel of Ag32,which is embraced by a robust cyclic anionic passivation layer of(KPO4)10.This Ag32 kernel can be viewed as a non-centered icosahedron Ag12 encaged into a dodecahedron Ag20,forming the silvery fullerene of Ag12@Ag2o.The anionic layer(KPO4)10 is located at the interlayer between the Ag32 kernel and Ag70 shell,passivating the Ag32 silvery fullerene and templating the Ag70 shell.The tBuPhS-and CF3COO-ligands on the silver shell show a regioselective arrangement with the 60 tBuPhS-ligands as expanders covering the upper and lower of the flying saucer and 10 CF3COO-as terminators neatly encircling the edges of the structure.In addition,Ag102 shows excellent photothermal conversion efficiency(η)from the visible to near-infrared region(η=67.1％±0.9％at 450 nm,60.9％±0.9％at 660 nm and 50.2％±0.5％at 808 nm),rendering it a promising material for photothermal converters and potential application in remote laser ignition.This work not only captures silver kernels with the topology of the smallest fullerene C20,but also provides a pathway for incorporating alkali metal(M)into coinage metal NCs via M-oxoanions.
查看更多>>摘要：Chemically modified superatoms have emerged as promising candidates in the new periodic table,in which Au13 and its doped MnAu13-n have been widely studied.However,their important counterpart,Ag13 artificial element,has not yet been synthesized.In this work,we report the synthesis of Ag13 nanoclusters using strong chelating ability and rigid ligands,that fills the gaps in the icosahedral superatomic metal clusters.After further doping Ag13 template with different degrees of Au atoms,we gained insight into the evolution of their optical properties.Theoretical calculations show that the kernel metal doping can modulate the transition of the excited-state electronic structure,and the electron transfer process changes from local excitation(LE)to charge transfer(CT)to LE.This study not only enriches the families of artificial superatoms,but also contributes to the understanding of the electronic states of superatomic clusters.
查看更多>>摘要：Covalent-organic frameworks(COFs)with photoinduced donor-acceptor(D-A)radical pairs show enhanced photocatalytic activity in principle.However,achieving long-lived charge separation in COFs proves challenging due to the rapid charge recombination.Here,we develop a novel strategy by combining[6+4]nodes to construct zyg-type 3D COFs,first reported in COF chemistry.This structure type exhibits a fused Olympic-rings-like shape,which provides a platform for stabilizing the photoinduced D-A radical pairs.The zyg-type COFs containing catalytically active moieties such as triphenylamine and phenothiazine(PTZ)show superior photocatalytic production rates of hydrogen peroxide(H2O2).Significantly,the photochromic radical states of these COFs show up to 400％enhancement in photocatalytic activity compared to the parent states,achieving a remarkable H2O2 synthesis rate of 3324 μmol g-1 h-1,which makes the PTZ-COF one of the best crystalline porous photocatalysts in H2O2 production.This work will shed light on the synthesis of efficient 3D COF photocatalysts built on topologies that can facilitate photogenerating D-A radical pairs for enhanced photocatalysis.
查看更多>>摘要：Radiotherapy is widely used for cancer treatment,but its clinical utility is limited by radioresistance and its inability to target metastases.Nanoscale metal-organic frameworks(MOFs)have shown promise as high-Z nanoradiosensitizers to enhance radiotherapy and induce immunostimulatory regulation of the tumor microenvironment.We hypothesized that MOFs could deliver small-molecule therapeutics to synergize with radiotherapy for enhanced antitumor efficacy.Herein,we develop a robust nanoradiosensitizer,GA-MOF,by conjugating a STING agonist,2',3'-cyclic guanosine monophosphate-adenosine monophosphate(GA),on MOFs for synergistic radiosensitization and STING activation.GA-MOF demonstrated strong anticancer efficacy by forming immune-cell-rich nodules(artificial leukocytoid structures)and transforming them into immunostimulatory hotspots with radiotherapy.Further combination with an immune checkpoint blockade suppressed distant tumors through systemic immune activation.Our work not only demonstrates the potent radiosensitization of GA-MOF,but also provides detailed mechanisms regarding MOF distribution,immune regulatory pathways and long-term immune effects.
查看更多>>摘要：Ultrasensitive protein identification is of paramount importance in basic research and clinical diagnostics but remains extremely challenging.A key bottleneck in preventing single-molecule protein sequencing is that,unlike the revolutionary nucleic acid sequencing methods that rely on the polymerase chain reaction(PCR)to amplify DNA and RNA molecules,protein molecules cannot be directly amplified.Decoding the proteins via amplification of certain fingerprints rather than the intact protein sequence thus represents an appealing alternative choice to address this formidable challenge.Herein,we report a proof-of-concept method that relies on residue-resolved DNA barcoding and composition code counting for amplifiable protein fingerprinting(AmproCode).In AmproCode,selective types of residues on peptides or proteins are chemically labeled with a DNA barcode,which can be amplified and quantified via quantitative PCR.The operation generates a relative ratio as the residue-resolved'composition code'for each target protein that can be utilized as the fingerprint to determine its identity from the proteome database.We developed a database searching algorithm and applied it to assess the coverage of the whole proteome and secretome via computational simulations,proving the theoretical feasibility of AmproCode.We then designed the residue-specific DNA barcoding and amplification workflow,and identified different synthetic model peptides found in the secretome at as low as the fmol/L level for demonstration.These results build the foundation for an unprecedented amplifiable protein fingerprinting method.We believe that,in the future,AmproCode could ultimately realize single-molecule amplifiable identification of trace complex samples without further purification,and it may open a new avenue in the development of next-generation protein sequencing techniques.
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