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Abstract Background and aim The association between gallstones/cholecystectomy and cancer remains inconclusive in the current literature. This study aimed to explore the causal connections between gallstones/cholecystectomy and cancer risk by utilizing a bidirectional two-sample multivariable Mendelian randomization approach with Genome-Wide Association Studies data. Methods Utilizing Genome-Wide Association Studies data from the UK Biobank and FinnGen, this research employed multivariable Mendelian randomization analyses to explore the impact of gallstones and cholecystectomy on the risk of 33 distinct cancer types. Instrumental variables for gallstones and cholecystectomy were carefully selected to ensure robust analyses, and sensitivity and heterogeneity tests were conducted to verify the findings’ validity. Results Multivariable Mendelian randomization analysis, incorporating data from more than 450,000 individuals for gallstones and cholecystectomy, revealed nuanced associations with cancer risk. Cholecystectomy was associated with a significantly increased risk of nonmelanoma skin cancer (OR = 1.59, 95% CI: 1.21 to 2.10, P = 0.001), while gallstones were linked to a decreased risk of the same cancer type (OR = 0.63, 95% CI: 0.47 to 0.84, P = 0.002). Interestingly, the analysis also suggested that cholecystectomy may lower the risk of small intestine tumors (OR = 0.18, 95% CI: 0.043 to 0.71, P = 0.015), with gallstones showing an inverse relationship, indicating an increased risk (OR = 6.41, 95% CI: 1.48 to 27.80, P = 0.013). Conclusions The multivariable Mendelian randomization analysis highlights the differential impact of gallstones and cholecystectomy on cancer risk, specifically for nonmelanoma skin cancer and small intestine tumors. These results underscore the importance of nuanced clinical management strategies and further research to understand the underlying mechanisms and potential clinical implications of gallstone disease and cholecystectomy on cancer risk.

Abstract Background Systemic conversion therapy provides patients with initially unresectable hepatocellular carcinoma (HCC) the chance to salvage radical liver resection and superior survival outcomes, but the optimal conversion strategy is unclear. Methods A systematic literature search was conducted on PubMed, EMBASE, Web of Science, Scopus, and the Cochrane Library between 2007 and 2024 focusing on studies reporting conversion therapy for HCC. The treatment groups were divided into Tyrosine kinase inhibitors (TKI), TKI plus loco-regional therapy (LRT), TKI plus anti-PD-1 therapy (TKI + PD-1), TKI + PD-1 + LRT, immune checkpoint inhibitors (ICI) plus LRT, and Atezolizumab plus bevacizumab (A + T) groups. The conversion to surgery rate (CSR), objective response rate (ORR), grade ≥ 3 treatment-related adverse events (AEs), overall survival (OS) and progression-free survival (PFS) were analyzed. Results 38 studies and 4,042 patients were included. The pooled CSR were 8% (95% CI, 5-12%) in TKI group, 13% (95% CI, 8-19%) in TKI + LRT group, 28% (95% CI, 19-37%) in TKI + PD-1 group, 33% (95% CI, 25-41%) in TKI + PD-1 + LRT group, 23% (95% CI, 1-46%) in ICI + LRT group, and 5% (95% CI, 3-8%) in A + T group, respectively. The pooled HR for OS (0.45, 95% CI, 0.35–0.60) and PFS (0.49, 95% CI, 0.35–0.70) favored survival benefit of conversion surgery. Subgroup analysis revealed that lenvatinib + PD-1 + LRT conferred higher CSR of 35% (95% CI, 26-44%) and increased ORR of 70% (95% CI, 56-83%). Conclusions The current study indicates that TKI + PD-1 + LRT, especially lenvatinib + PD-1 + LRT, may be the superior conversion therapy with a manageable safety profile for patients with initially unresectable HCC. The successful conversion therapy favors the superior OS and PFS compared with systemic treatment alone. Trial registration International prospective register of systematic reviews (PROSPERO) (registration code: CRD 42024495289).

Abstract Gut microbiota can regulate the metabolic and immunological aspects of ischemic stroke and modulate the treatment effects. The present study aimed to identify specific changes in gut microbiota in patients with large vessel occlusion (LVO) ischemic stroke and assess the potential association between gut microbiota and clinical features of ischemic stroke. A total of 63 CSVD patients, 64 cerebral small vessel disease (CSVD) patients, and 36 matching normal controls (NCs) were included in this study. The fecal samples were collected for all participants and analyzed for gut microbiota using 16S rRNA gene sequencing technology. The abundances of five gut microbiota, including genera Bifidobacterium, Butyricimonas, Blautia, and Dorea and species Bifidobacterium_longum, showed significant changes with high specificity in the LVO patients as compared to the NCs and CSVD patients. In LVO patients, the genera Bifidobacterium and Blautia and species Bifidobacterium_longum were significantly correlated with the National Institutes of Health Stroke Scale (NIHSS) scores at the admission and discharge of the patients. Serum triglyceride levels could significantly affect the association of the abundance of genus Bifidobacterium and species Bifidobacterium_longum with the NIHSS scores at admission and modified Rankin Scale (mRS) at discharge in LVO patients. The identification of five gut microbiota with high specificity were identified in the early stage of LVO stroke, which contributed to performed an effective clinical management for LVO ischemic stroke.

To evaluate the efficacy of the 18F–AlF-NOTA-RGD2 positron emission tomography (PET)/computed tomography (CT) molecular probe for the noninvasive staging of liver fibrosis in mini pigs, a potential alternative to invasive diagnostic methods was revealed. This study used 18F–AlF-NOTA-RGD2 PET/CT imaging of mini pigs to assess liver fibrosis. The methods included synthesis and quality control of the molecular probe, establishment of an animal model of liver fibrosis, blood serum enzymatic tests, histopathological examination, PET/CT imaging, collagen content and expression, and mitochondrial reserve function assessment. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe effectively differentiated various stages of liver fibrosis in mini pigs. Blood serum enzymatic tests revealed distinct stages of liver fibrosis, revealing significant increases in AST, ALT, TBIL, and DBIL levels as fibrosis advanced. Notably, ALT levels increased markedly in severe fibrosis patients. A gradual increase in collagen deposition and increasing α-SMA RNA expression and protein levels effectively differentiated between mild and severe fibrosis stages. Pathological examinations and Sirius Red staining confirmed these findings, highlighting substantial increases in collagen accumulation. PET/CT imaging results aligned with histopathological findings, showing that increased radiotracer uptake correlated with fibrosis severity. Assessments of mitochondrial function revealed a decrease in total liver glutathione content and mitochondrial reserve capacity, especially in patients with severe fibrosis. The 18F–AlF-NOTA-RGD2 PET/CT molecular probe is a promising tool for the noninvasive assessment of liver fibrosis, offering potential benefits over traditional diagnostic methods in hepatology.

Abstract Microvascular invasion (MVI) has been widely valued in the field of liver surgery because MVI positivity indicates poor prognosis in hepatocellular carcinoma (HCC) patients. However, the potential molecular mechanism underlying the poor prognosis of MVI‐positive HCC patients is unclear. Therefore, this study focused on identifying the key genes leading to poor prognosis in patients with a high degree of malignancy of HCC by examining the molecular signaling pathways in MVI‐positive HCC patients. Through RNA sequencing, TOX high mobility group box family member 3 (TOX3) was demonstrated to be significantly highly expressed in MVI‐positive HCC tissues, which was associated with poor prognosis. The results of in vivo and in vitro showed that TOX3 can promote the oncogenesis and development of HCC by targeting key molecules of the MAPK and EMT signaling pathways. The IP‐MS results indicated that proteasome degradation of TOX3 in HCC cells is potentially mediated by a tripartite motif containing 56 (TRIM56, an E3 ligase) in HCC cells. Inhibiting TRIM56 enhances TOX3 protein levels. Overall, our study identified TOX3 as a key gene in the MAPK and EMT signaling pathways in HCC, and its overexpression confers significant proliferation and invasiveness to tumor cells.

The secure computation of symmetric encryption schemes using Yao’s garbled circuits, such as AES, allows two parties, where one holds a plaintext block m and the other holds a key k, to compute Enc(k,m) without leaking m and k to one another. Due to its wide application prospects, secure AES computation has received much attention. However, the evaluation of AES circuits using Yao’s garbled circuits incurs substantial communication overhead. To further improve its efficiency, this paper, upon observing the special structures of AES circuits and the symmetries of an S-box, proposes a novel ciphertext reduction scheme for garbling an S-box in the last SubBytes step. Unlike the idea of traditional Yao’s garbled circuits, where the circuit generator uses the input wire labels to encrypt the corresponding output wire labels, our garbling scheme uses the input wire labels of an S-box to encrypt the corresponding “flip bit strings”. This approach leads to a significant performance improvement in our garbling scheme, which necessitates only 28 ciphertexts to garble an S-box and a single invocation of a cryptographic primitive for decryption compared to the best result in previous work that requires 8×28 ciphertexts to garble an S-box and multiple invocations of a cryptographic primitive for decryption. Crucially, the proposed scheme provides a new idea to improve the performance of Yao’s garbled circuits. We analyze the security of the proposed scheme in the semi-honest model and experimentally verify its efficiency.

The convergence of software-defined networking (SDN) and the Internet of Things (IoT) provides a scalable method for handling the considerable volumes of data produced by IoT devices. However, the lack of appropriate security measures can lead to unauthorized access to sensitive data, potential breaches, and privacy violations, as well as time-consuming and inefficient data retrieval methods in SDN-IoT systems that require decrypting the entire dataset. To address these challenges, this article proposes the time-attribute-based access control scheme in SDN-IoT (TAAC). The TAAC scheme combines ciphertext-policy attribute-based encryption with a novel time-attribute-based access tree to ensure fine-grained access control on time and attributes, enabling secure ciphertext interaction and information sharing across domains. Furthermore, the TAAC scheme also incorporates searchable encryption, which enhances the efficiency of data retrieval. By implementing searchable encryption techniques, the data receiver can generate trapdoors to search and retrieve specific encrypted data without the need to decrypt the entire dataset. In summary, the TAAC scheme improves storage efficiency and computation, enhances scalability, and provides robust security, offering an efficient and secure solution for ciphertext sharing in SDN-IoT environments. Experimental results have demonstrated that the TAAC scheme shows excellent performance and outperforms other attribute-based searchable encryption algorithms.

The Tengchong Cenozoic volcano is located near the collision boundary between the Indian and Eurasian plates. The tectonic activity in this area is strong, and the volcano has a potential for eruption. Studying the origin of the Tengchong volcano is important for understanding plate subduction processes and the mechanism of volcano eruption. This review first summarizes the latest researches on the origin of the Tengchong volcano, including new advances in geophysics and geochemistry, and then discusses the magma source and deep dynamic mechanism. These studies have found that the genesis of Tengchong volcanism is mainly related to plate subduction. The subducted residual oceanic plate and the currently subducting Indian plate may both contribute to the source of metasomatic materials. The oceanic plate released melt and fluid to form metasomatized asthenospheric and lithospheric mantles, and Tengchong magma originated from the mixing of lithospheric and asthenosphere mantle melts. The metasomatized lithospheric mantle is characterized by low 3He/4He (< 7.0 Ra) and Nb/La (average of 0.36) ratios as well as high 87Sr/86Sr (average of 0.707928) and La/Yb (average of 22.0) ratios. In contrast, the enriched asthenospheric mantle is characterized by high 3He/4He (> 7.0 Ra) and Nb/La (average of 0.52) ratios with relatively low 87Sr/86Sr (average of 0.706708) and La/Yb (average of 17.0) ratios. The increasing trend of 3He/4He ratios and decreasing trend of 87Sr/86Sr ratios over time suggest that the contribution of the metasomatized lithospheric mantle decreased relative to that of the enriched asthenosphere after the late Pleistocene, reflecting the progressive lithospheric extension and thinning. Tengchong basalts do not show clear correlation between 87Sr/86Sr ratio and SiO2 content, whereas basaltic andesite, andesite, and dacite display positive correlation between 87Sr/86Sr ratio and SiO2 content. This phenomenon indicates that Tengchong basalt suffered limited crustal contamination, while basaltic andesite, andesite, and dacite underwent obvious crustal contamination. Moreover, seismic imaging along with magnetotelluric and geothermal studies revealed several magma chambers (low-speed anomalies) in the crust beneath the Tengchong volcano. However, the size and depth of the magma chambers vary between different studies. The low-velocity bodies in the crust extend downward to the upper mantle, which may indicate that the magma chambers in the crust are fed by hot materials from the upper mantle. However, a consensus on the origin of hot materials has yet to be reached. Seismic tomography studies suggest that hot materials could be generated from the dehydration of the stagnant slab in the mantle transition zone, tearing of the subducted plate, or slab rollback. Differences in seismic imaging results may be caused by the limited observation data, data imaging methods, and the multi-solution of geophysical inversion. The utilization of more data and advanced geophysical methods will help obtain high-resolution imaging results to further constrain the origin of the Tengchong volcano.

With the continuous and rapid development of Cloud Computing, Big Data and Internet of Things, it is extremely critical to protect data with homomorphism, privacy and integrity. For this, Rezaeibagha et al. proposed a new cryptographic primitive, called homomorphic signcryption. However, the current homomorphic signcryption schemes either only support linear computation or are built on non-standard assumption. Therefore, it is interesting to design a leveled fully homomorphic signcryption (FHSC) scheme from the standard assumption. In this work, we present a leveled FHSC scheme from lattices. For this, we exert classical sign-then-encrypt method and surmount the difficulty of homomorphic multiplicative evaluation in the way of encrypting every elements. Moreover, we prove its indistinguishability against chosen plaintext attacks (IND-CPA) and strong unforgeability (SUF) under hard problems of standard lattices.

C 5 –C 7 light hydrocarbons are important components in petroleum and are extensively employed as an auxiliary approach in petroleum research. Consensus on the mechanism of light hydrocarbon generation has not yet been achieved. In this study, 20 gas samples were collected from the western part and northern margin of the Qaidam Basin. The molecular and carbon isotopic compositions of C 1 –C 3 gaseous hydrocarbons and C 5 –C 7 light hydrocarbons, as well as the carbon isotopes of oils were analyzed. Based on the relationships between carbon isotopes ( 13 C) of individual light hydrocarbons and calculated vitrinite reflectance, it suggests that organic matters play a fundamental role in the carbon isotopes of light hydrocarbons, and maturity mainly affects the carbon isotopes of n -alkanes in light hydrocarbons. In addition, carbon isotopic differences between n -, iso - and cyclo -alkanes indicate that light hydrocarbons with different structures are produced from various biological precursors. Besides, carbon isotopes of individual light hydrocarbons can be used to estimate the δ 13 C kerogen and distinguish cracked gas. On the one hand, small isotope fractionation between iso -alkanes and kerogen is observed. Average carbon isotopic compositions of iso -pentane ( i -C 5 ), 2-methylpentane (2-MC 5 ) and 3-methylpentane (3-MC 5 ) can provide a similar δ 13 C kerogen with actual values. On the other hand, the carbon isotopic difference between 2-MC 5 and n -C 6 generally decreases with increasing maturity. Combined with the parameter (2-MC 6 + 3-MC 6 )/ n -C 6 , kerogen-cracked gases are characterized by high δ 13 C 2MC5 –δ 13 C nC6 and low (2-MC 6 + 3-MC 6 )/ n -C 6 values, whereas oil-cracked gases exhibit the opposite features.

Phenotypic plasticity is the ability of an individual genotype to express phenotype variably in different environments. This study investigated the plasticity of yield-related traits of bread wheat by utilising 225 doubled haploid (DH) lines developed from cv. Westonia and cv. Kauz, through two field trials in Western Australia. Plasticity was quantified via two previously published methods: responsiveness to varying ecological conditions and slopes of reaction norms. The spikelets/spike was the most plastic trait, with an overall plasticity of 1.62. The least plastic trait was grain protein content, with an overall plasticity of 0.79. The trait hierarchy based on phenotypic plasticity was spikelets/spike > thousand kernel weight > seed number > seed length > grain yield > grain protein content. An increase in yield plasticity of 0.1 was associated with an increase in maximum yield of 4.45 kg ha−1. The plasticity of seed number and grain protein content were significantly associated with yield plasticity. The maximal yield was positively associated with spikelets/spike and grain yield, whereas it negatively associated with grain protein content. In contrast, the minimal yield was found to be negatively related to the plasticity of spikelets/spike and the plasticity of grain yield, whereas it was not related to grain protein content plasticity. Seed number and seed length exhibited plastic responses at the higher fertilisation state while remaining relatively stable at the lower fertilisation state for the wheat DH population. The finding of the current study will play a key role in wheat improvement under the changing climate. Seed length and seed number should be the breeding target for achieving stable yield in adverse environmental conditions.

Reproductive stage frost poses a major constraint for wheat production in countries such as Australia. However, little progress has been made in identifying key genes to overcome the constraint. In the present study, a severe frost event hit two large-scale field trials consisting of six doubled haploid (DH) wheat populations at reproductive stage (young microspore stage) in Western Australia, leading to the identification of 30 robust frost QTL on 17 chromosomes. The major 18 QTL with the phenotype variation over 9.5% were located on 13 chromosomes including 2A, 2B, 2D, 3A, 4A, 4B, 4D, 5A, 5D, 6D, 7A, 7B and 7D. Most frost QTL were closely linked to the QTL of anthesis, maturity, Zadok stages as well as linked to anthesis related genes. Out of those, six QTL were repetitively detected on the homologous regions on 2B, 4B, 4D, 5A, 5D, 7A in more than two populations. Results showed that the frost damage is associated with alleles of Vrn-A1a, Vrn-D1a, Rht-B1b, Rht-D1b, and the high copy number of Ppd-B1. However, anthesis QTL and anthesis related genes of Vrn-B1a and TaFT3-1B on chromosomes 5B and 1B did not lead to frost damage, indicating that these early-flowering phenotype related genes are compatible with frost tolerance and thus can be utilised in breeding. Our results also indicate that wild-type alleles Rht-B1a and Rht-D1a can be used when breeding for frost-tolerant varieties without delaying flowering time.

BackgroundNon-valvular atrial fibrillation (NVAF) is the most common cause of cardiogenic cerebral embolism (CCE). However, the underlying mechanism between cerebral embolism and NVAF is indefinite, and there is no effective and convenient biomarker to identify potential risk of CCE in patients with NVAF in clinic. The present study aims to identify risk factors for interpreting the potential association of CCE with NVAF and providing valuable biomarkers to predict the risk of CCE for NVAF patients.Methods641 NVAF patients diagnosed with CCE and 284 NVAF patients without any history of stroke were recruited in the present study. Clinical data including demographic characteristics, medical history, and clinical assessments, were recorded. Meanwhile, Blood cell counts, lipid profiles, high-sensitivity C-reactive protein, and coagulation function-related indicators were measured. Least absolute shrinkage and selection operator (LASSO) regression analysis was utilized to build a composite indicator model based on the blood risk factors.Results(1) CCE patients had significantly increased neutrophil-to-lymphocyte ratio, platelet-to-lymphocyte ratio (PLR), and D-dimer levels as compared with patients in the NVAF group, and these three indicators can distinguish CCE patients from ones in the NVAF group with an area under the curve (AUC) value of over 0.750, respectively. (2) Using the LASSO model, a composite indicator, i.e., the risk score, was determined based on PLR and D-dimer and displayed differential power for distinguishing CCE patients from NVAF patients with an AUC value of over 0.934. (3) The risk score was positively correlated with the National Institutes of Health Stroke Scale and CHADS2 scores in CCE patients. (4) There was a significant association between the change value of the risk score and the recurrence time of stroke in initial CCE patients.ConclusionsThe PLR and D-dimer represent an aggravated process of inflammation and thrombosis in the occurrence of CCE after NVAF. The combination of these two risk factors can contribute to identifying the risk of CCE for patients with NVAF with an accuracy of 93.4%, and the greater in change of composite indicator, the shorter in the recurrence of CCE for NVAF patients.

The Tengchong Cenozoic volcanic field lies in SE margin of the Tibetan Plateau. The basalts of the Tengchong field exhibit evident spatial-temporal variations, but consensus on their meaning has not been reached yet. In this study, we collected basalts from western, central and eastern areas in the Tengchong volcanic field and measured the whole-rock and olivine major and trace elements of basalts. Tengchong basalts exhibit remarkable chemical and isotopic diversity, showing a strong correlation with eruption locations and ages. Specifically, basalts in the western and eastern areas (formed at 7.2–2.8 Ma) are characterized by high 87Sr/86Sr and low 3He/4He ratios, while those in the central area (formed at 0.6–0.02 Ma) feature low 87Sr/86Sr and high 3He/4He ratios. Based on the temperature- and pressure-dependent elemental partition coefficients, this phenomenon is interpreted as mainly caused by the difference in lithospheric thickness among these areas. On the one hand, the estimated primary magmas in the eastern and western areas show higher SiO2, Na2O, (La/Sm)N, Hf/Lu and Ba/Zr ratios than those in the central area. On the other hand, the Ni contents in olivine phenocrysts are higher in the western and eastern areas than in the central area. As different amounts of extension result in different degrees of decompression of the asthenosphere, finally influencing the compositional variation of magmas, these results indicate that the lithosphere in the eastern and western areas is thicker than that in the central area. In addition, basalts erupted in the eastern and western areas are older than those in the central area, suggesting lithospheric thinning. We propose that lithospheric extension due to slab rollback may have caused lithospheric thinning. In addition, according to the different deformation modes of the crust and lithospheric mantle, our study supports mantle-crust decoupling south of ∼26°N in SE margin of the Tibetan Plateau.

ObjectiveAnxiety is one of the most common psychiatric symptoms of Parkinson’s disease (PD), and brain iron deposition is considered to be one of the pathological mechanisms of PD. The objective of this study was to explore alterations in brain iron deposition in PD patients with anxiety compared to PD patients without anxiety, especially in the fear circuit.MethodsSixteen PD patients with anxiety, 23 PD patients without anxiety, and 26 healthy elderly controls were enrolled prospectively. All subjects underwent neuropsychological assessments and brain magnetic resonance imaging (MRI) examinations. Voxel-based morphometry (VBM) was used to study morphological brain differences between the groups. Quantitative susceptibility mapping (QSM), an MRI technique capable of quantifying susceptibility changes in brain tissue, was used to compare susceptibility changes in the whole brain among the three groups. The correlations between brain susceptibility changes and anxiety scores quantified using the Hamilton Anxiety Rating Scale (HAMA) were compared and analyzed.ResultsPD patients with anxiety had a longer duration of PD and higher HAMA scores than PD patients without anxiety. No morphological brain differences were observed between the groups. In contrast, voxel-based and ROI-based QSM analyses showed that PD patients with anxiety had significantly increased QSM values in the medial prefrontal cortex, anterior cingulate cortex, hippocampus, precuneus, and angular cortex. Furthermore, the QSM values of some of these brain regions were positively correlated with the HAMA scores (medial prefrontal cortex: r = 0.255, p = 0.04; anterior cingulate cortex: r = 0.381, p

With the deepening of research, how to construct a fully homomorphic signcryption scheme based on standard assumptions is a problem that we need to solve. For this question, recently, Jin et al. proposed a leveled fully homomorphic signcryption scheme from standard lattices. However, when verifying, it is supposed to unsigncrypt first as they utilize sign-then-encrypt method. This leads to users being unable to verify the authenticity of the data first, which resulting in the waste of resources. This raises another question of how to construct an fully homomorphic signcryption (FHSC) scheme with public verifiability. To solve this problem, we propose a leveled fully homomorphic signcryption scheme that can be publicly verified and show its completeness, IND-CPA security, and strong unforgeability.

Abstract Hepatocellular carcinoma (HCC) is the sixth most common primary cancer with an unsatisfactory long-term survival. Gain of function mutations of PIK3CA occur in a subset of human HCC. Alpelisib, a selective PIK3CA inhibitor, has been approved by the FDA to treat PIK3CA mutant breast cancers. In this manuscript, we evaluated the therapeutic efficacy of alpelisib, either alone or in combination, for the treatment of HCC. We tested alpelisib in mouse HCC induced by hydrodynamic injection of c-Met/PIK3CA(H1047R) (c-Met/H1047R), c-Met/PIK3CA(E545K) (c-Met/E545K), and c-Met/sgPten gene combinations. Alpelisib slowed down the growth of c-Met/H1047R and c-Met/E545K HCC but was ineffective in c-Met/sgPten HCC. Mechanistically, alpelisib inhibited p-ERK and p-AKT in c-Met/H1047R and c-Met/E545K HCC progression but did not affect the mTOR pathway or genes involved in cell proliferation. In human HCC cell lines transfected with PIK3CA(H1047R), alpelisib synergized with the mTOR inhibitor MLN0128 or the CDK4/6 inhibitor palbociclib to suppress HCC cell growth. In c-Met/H1047R mice, alpelisib/MLN0128 or alpelisib/palbociclib combination therapy caused tumor regression. Our study demonstrates that alpelisib is effective for treating PIK3CA-mutated HCC by inhibiting MAPK and AKT cascades. Furthermore, combining alpelisib with mTOR or CDK4/6 inhibitors has a synergistic efficacy against PIK3CA-mutated HCC, providing novel opportunities for precision medicine against HCC.

BackgroundReliable and individualized biomarkers are crucial for identifying early cognitive impairment in subcortical small-vessel disease (SSVD) patients. Personalized brain age prediction can effectively reflect cognitive impairment. Thus, the present study aimed to investigate the association of brain age with cognitive function in SSVD patients and assess the potential value of brain age in clinical assessment of SSVD.Materials and methodsA prediction model for brain age using the relevance vector regression algorithm was developed using 35 healthy controls. Subsequently, the prediction model was tested using 51 SSVD patients [24 subjective cognitive impairment (SCI) patients and 27 mild cognitive impairment (MCI) patients] to identify brain age-related imaging features. A support vector machine (SVM)-based classification model was constructed to differentiate MCI from SCI patients. The neurobiological basis of brain age-related imaging features was also investigated based on cognitive assessments and oxidative stress biomarkers.ResultsThe gray matter volume (GMV) imaging features accurately predicted brain age in individual patients with SSVD (R2 = 0.535, p < 0.001). The GMV features were primarily distributed across the subcortical system (e.g., thalamus) and dorsal attention network. SSVD patients with age acceleration showed significantly poorer Mini-Mental State Examination and Montreal Cognitive Assessment (MoCA) scores. The classification model based on GMV features could accurately distinguish MCI patients from SCI patients (area under the curve = 0.883). The classification outputs of the classification model exhibited significant associations with MoCA scores, Trail Making Tests A and B scores, Stroop Color and Word Test C scores, information processing speed total scores, and plasma levels of total antioxidant capacity in SSVD patients.ConclusionBrain age can be accurately quantified using GMV imaging data and shows potential clinical value for identifying early cognitive impairment in SSVD patients.

Heat stress is a primary constraint to Australia's barley production. In addition to impacting grain yield, it adversely affects physical grain quality (weight and plumpness) and market value. The incidence of heat stress during grain filling is rising with global warming. However, breeding for new superior heat-tolerant genotypes has been challenging due to the narrow window of sensitivity, the unpredictable nature of heat stress, and its frequent co-occurrence with drought stress. Greater scientific knowledge regarding traits and mechanisms associated with heat tolerance would help develop more efficient selection methods. Our objective was to assess 157 barley varieties of contrasting genetic backgrounds for various developmental, agro-morphological, and physiological traits to examine the effects of heat stress on physical grain quality. Delayed sowing (i.e., July and August) increased the likelihood of daytime temperatures above 30°C during grain-filling. Supplementary irrigation of field trials ensured a reduced impact of drought stress. Heat tolerance appeared to be the primary factor determining grain plumpness. A wide variation was observed for heat tolerance, particularly among the Australian varieties. Genotypic variation was also observed for grain weight, plumpness, grain growth components, stay-green and stem water-soluble carbohydrates (WSC) content, and mobilisation under normal and delayed sown conditions. Compared to normal sowing, delayed sowing reduced duration of developmental phases, plant height, leaf size, head length, head weight, grain number, plumpness, grain width and thickness, stem WSC content, green leaf area retention, and harvest index (HI), and increased screenings, grain length, grain-filling rate (GFR), WSC mobilisation efficiency (WSCME), and grain protein content. Overall, genotypes with heavier and plumper grains under high temperatures had higher GFR, longer grain-filling duration, longer green leaf area retention, higher WSCME, taller stature, smaller leaf size, greater HI, higher grain weight/plumpness potentials, and earlier flowering. GFR played a significant role in determining barley grain weight and plumpness under heat-stress conditions. Enhancing GFR may provide a new avenue for improving heat tolerance in barley.

Based on Sun et al.'s multi-client symmetric searchable encryption (SSE) scheme (at ESORICS 2016), and combining Zhao's identity-concealed authenticated encryption (CCS 2016), a new SSE scheme with multi-data-owner functionalities is proposed. By setting two key generation centers, our scheme first implements multi-data-owner SSE. In particular, compared with Sun et al.'s scheme, the new scheme not only meets the same security requirements stated by them, but also further strengthens the securities of the same category relevant scheme by providing identity-concealment, authentication of data user to server and confidentiality of search token. The identity-concealment aims to provide privacy protection (Forward ID-Privacy) for data users by hiding their identity information, while the authentication is to resist the camouflage attack by applying certificate-based mechanism to our scheme. In particular, the confidentiality of the search token provides replay-attack-resistant by encrypting the plaintext search token generated by data user. While in other works, the adversary can employ the previously generated plaintext search tokens to force the server to perform the same search queries. Furthermore, by efficiency analysis, our scheme reaches almost the same level of efficiency as Sun et al.'s scheme.

Abstract Powdery mildew isa major disease of barley (Hordeum vulgare L.) for which breeders have traditionally relied on dominant, pathogen race‐specific resistance genes for genetic control. Directional selection pressures in extensive monocultures invariably result in such genes being overcome as the pathogen mutates to evade recognition. This has led to a widespread reliance on fungicides and a single broad‐spectrum recessive resistance provided by the mlo gene. The range of resistance genes and alleles found in wild crop relatives and landraces has been reduced in agricultural cultivars through an erosion of genetic diversity during domestication and selective breeding. Three novel major‐effect adult plant resistance (APR) genes from landraces, designated Resistance to Blumeria graminis f. sp. hordei (Rbgh1 to Rbgh3), were identified in the terminal regions of barley chromosomes 5HL, 7HS, and 1HS, respectively. The phenotype of the new APR genes showed neither pronounced penetration resistance, nor the spontaneous necrosis and mesophyll cell death typical of mlo resistance, nor a whole epidermal cell hypersensitive response, typical of race‐specific resistance. Instead, resistance was localized to the site of attempted penetration in an epidermal cell and was associated with cell wall appositions and cytosolic vesicle‐like bodies, and lacked strong induction of reactive oxygen species. The APR genes exhibited differences in vesicle‐like body sizes, their distribution, and the extent of localized 3,3‐diaminobenzidine staining in individual doubled haploid lines. The results revealed a set of unique basal penetration resistance genes that offer opportunities for combining different resistance mechanisms in breeding programs for robust mildew resistance.

Nitrogen (N) fertilizer is largely responsible for barley grain yield potential and quality, yet excessive application leads to environmental pollution and high production costs. Therefore, efficient use of N is fundamental for sustainable agriculture. In the present study, we investigated the performance of 282 barley accessions through hydroponic screening using optimal and low NH4NO3 treatments. Low-N treatment led to an average shoot dry weight reduction of 50%, but there were significant genotypic differences among the accessions. Approximately 20% of the genotypes showed high (>75%) relative shoot dry weight under low-N treatment and were classified as low-N tolerant, whereas 20% were low-N sensitive (≤55%). Low-N tolerant accessions exhibited well-developed root systems with an average increase of 60% in relative root dry weight to facilitate more N absorption. A genome-wide association study (GWAS) identified 66 significant marker trait associations (MTAs) conferring high nitrogen use efficiency, four of which were stable across experiments. These four MTAs were located on chromosomes 1H(1), 3H(1), and 7H(2) and were associated with relative shoot length, relative shoot and root dry weight. Genes corresponding to the significant MTAs were retrieved as candidate genes, including members of the asparagine synthetase gene family, several transcription factor families, protein kinases, and nitrate transporters. Most importantly, the high-affinity nitrate transporter 2.7 (HvNRT2.7) was identified as a promising candidate on 7H for root and shoot dry weight. The identified candidate genes provide new insights into our understanding of the molecular mechanisms driving nitrogen use efficiency in barley and represent potential targets for genetic improvement.

The first identity-based fully homomorphic encryption (IBFHE) scheme was constructed from identity-based encryption (IBE) and lattice-based cryptography by Gentry, Sahai, and Waters in CRYPTO 2013. Their IBFHE scheme is improved in this paper, exploiting Alperin-Sheriff and Peikert's tight and simple noise analysis method when evaluating homomorphically and Micciancio and Peikert's powerful and novel trapdoor. Furthermore, using the masking scheme(Mukherjee and Wichs in EUROCRYPT 2016), we construct an efficient multi-identity fully homomorphic encryption (MIFHE) scheme by expanding a “fresh” ciphertext under a single identity key to an “expanded” one under a combined key that enables ciphertexts under different identities to be homomorphically evaluated.

The previously proposed short comparable encryption (SCE) scheme can infer the plaintext relationship by comparing the ciphertexts relationship as well as ensuring data security in Internet of things.Unfortunately,it will incur high storage and computational burden during the process of comparing ciphertexts and generating tokens.To this end,an efficient short comparable encryption scheme called SCESW was proposed,which was utilizing the sliding window method with the same size window.Formal security analysis shows that the scheme can guarantee weak indistinguishability in standard model as well as data security and integrity.The experimental results demonstrate that the storage of the SCESW scheme is 1 t (t＞1) times shorter than that of the SCE scheme and the efficiency of the SCESW scheme is superior to that of the SCE scheme.

31 natural gases in the western Qaidam Basin of China were collected and analyzed for gas composition including light hydrocarbons (C5-C7) and carbon isotopic characteristics. Based on genetic type obtained from C1-C3 and C7 fractions, four types of gases are identified: oil-type gas, coal-type gas, biodegraded gas, and mixed gas. The oil-type gas is the predominant-type gas in the western Qaidam Basin; coal-type gas is mainly distributed in the Zhahaquan and Nanyishan fields; mixed gas is mainly in the Zhahaquan, Wunan, and Nanyishan fields; and biodegraded gas is mainly distributed in the Huatugou and Yuejinerhao fields. According to the empirical relationship between δ13C1 and the equivalent vitrinite reflectance (Ro, %) of source rock, the Ro values of gas range from 0.6% to 1.5%, with an average value of 0.9%. The generation temperatures of major reservoired hydrocarbons (GTMRH) calculated from the C7 components range from 115.6°C to 141.7°C, with an average value of 126.5°C. These two maturity indicators have relatively positive correlation and reveal that the maturity of gas increases from west to east in the southwestern Qaidam Basin. Moreover, combining GTMRH with the homogenous temperature of petroleum inclusions, it is inferred that major petroleum charge in the western Qaidam Basin mainly occurred during the late period of the Himalayan movement. Deep hydrocarbon fluid sources were found in the Shizigou, Yingdong, Zhahaquan, and Nanyishan fields; thus, the deep reservoirs of paleouplifts adjacent to the hydrocarbon-generating depressions are estimated as a favorable area for further exploration in the western Qaidam Basin.

The ancestry of the European bison (wisent) remains a mystery. Here, Cooper and colleagues examine ancient DNA from fossil remains of extinct bison, and reveal the wisent originated through the hybridization of the extinct Steppe bison and ancestors of modern cattle.

There are vast resources of oil shale in the Chang-7 section of the Upper Triasic Yanchang Formation, Ordos Basin, China. They would provide secure access to transportation fuels, if utilized in an effective, economic and environmental manner. A Chang-7 oil shale sample containing pyrite has been pyrolysed in a thermogravimetric analyzer at constant heating rates of 5, 10, 20℃/min up to 1150℃ with nitrogen as purge gas. Meanwhile, the pyrolysis-gas chromatograph-mass spectrometry experiments were performed on parallel samples of Chang-7 oil shale sample at 20℃/min in the four temperature sections, ranging from 100 to 700℃ to understand the decomposition mechanism. The initial decomposition temperature and the final decomposition temperature of hydrocarbonaceous material were about 367℃ and 521℃ (average values), respectively, which raised with the increase of heating rate. The decomposition of pyrite began to take place over 500℃, and the pyrolysates involving sulfur compounds are harmful to the environment and corrode the equipment. Thus, we recommended that the final temperature of Chang-7 oil shale pyrolysis was best not to exceed 550℃ considering the heating rate to avoid environmental pollution and damage of the instruments. Chang-7 oil shale exhibited a single stage decomposition in the range of about 367–521℃, representing the rearrangement of kerogen molecules in the temperature range of 100–350℃. The activation energies of kerogen decomposition were calculated using Coats–Redfern method at different heating rate. We found that both activation energy and pre-exponential factor increased with an increasing heating rate. Finally, the DTA curves of Chang-7 oil shale verified the reliability of the calculated activation energies.

The principal features of primary zone determine the performance parameters of the whole combustion chamber, such as the pollutant emissions and combustion efficiency. In this work, flow field and major species concentration measurements are conducted in the primary zone of an aero-engine combustion chamber. The operating conditions such as air inlet temperature, chamber pressure, and air-to-fuel ratio are chosen to replicate the realistic operating conditions. The velocity field and streamlines are obtained by particle imaging velocimetry technology. The concentrations of major species are acquired by a spontaneous Raman scattering system. This article validates the feasibility of two laser diagnostic measurement techniques and presents the initial results under realistic aero-engine conditions.

An Identity-based encryption (IBE) simplifies key management by taking users’ identities as public keys. However, how to dynamically revoke users in an IBE scheme is not a trivial problem. To solve this problem, IBE scheme with revocation (namely revocable IBE scheme) has been proposed. Apart from those lattice-based IBE, most of the existing schemes are based on decisional assumptions over pairing-groups. In this paper, we propose a revocable IBE scheme based on a weaker assumption, namely Computational Diffie-Hellman (CDH) assumption over non-pairing groups. Our revocable IBE scheme is inspired by the IBE scheme proposed by Döttling and Garg in Crypto2017. Like Döttling and Garg’s IBE scheme, the key authority maintains a complete binary tree where every user is assigned to a leaf node. To adapt such an IBE scheme to a revocable IBE, we update the nodes along the paths of the revoked users in each time slot. Upon this updating, all revoked users are forced to be equipped with new encryption keys but without decryption keys, thus they are unable to perform decryption any more. We prove that our revocable IBE is adaptive IND-ID-CPA secure in the standard model. Our scheme serves as the first revocable IBE scheme from the CDH assumption. Moreover, we extend our scheme to support Decryption Key Exposure Resistance (DKER) and also propose a server-aided revocable IBE to decrease the decryption workload of the receiver. In our schemes, the size of updating key in each time slot is only related to the number of newly revoked users in the past time slot.

The pig, a representative of the artiodactyla clade, is one of the first animals domesticated, and has become an important agriculture animal as one of the major human nutritional sources of animal based protein. The pig is also a valuable biomedical model organism for human health. The pig's importance to human health and nutrition is reflected in the decision to sequence its genome (3X). As an animal species with its wild ancestors present in the world, the pig provides a unique opportunity for tracing mammalian evolutionary history and defining signatures of selection resulting from both domestication and natural selection. Completion of the pig genome sequencing project will have significant impacts on both agriculture and human health. Following the pig whole genome sequence drafts, along with large-scale polymorphism data, it will be possible to conduct genome sweeps using association mapping, and identify signatures of selection. Here, we provide a description of the pig genome sequencing project and perspectives on utilizing genomic technologies to exploit pig genome evolution and the molecular basis for phenotypic traits for improving pig production and health.

Epigenetic changes to gene expression can result in heritable phenotypic characteristics that are not encoded in the DNA itself, but rather by biochemical modifications to the DNA or associated chromatin proteins. Interposed between genes and environment, these epigenetic modifications can be influenced by environmental factors to affect phenotype for multiple generations. This raises the possibility that epigenetic states provide a substrate for natural selection, with the potential to participate in the rapid adaptation of species to changes in environment. Any direct test of this hypothesis would require the ability to measure epigenetic states over evolutionary timescales. Here we describe the first single-base resolution of cytosine methylation patterns in an ancient mammalian genome, by bisulphite allelic sequencing of loci from late Pleistocene Bison priscus remains. Retrotransposons and the differentially methylated regions of imprinted loci displayed methylation patterns identical to those derived from fresh bovine tissue, indicating that methylation patterns are preserved in the ancient DNA. Our findings establish the biochemical stability of methylated cytosines over extensive time frames, and provide the first direct evidence that cytosine methylation patterns are retained in DNA from ancient specimens. The ability to resolve cytosine methylation in ancient DNA provides a powerful means to study the role of epigenetics in evolution.

BACKGROUND: Salvage liver transplantation (SLT) is restricted to patients who develop hepatocellular carcinoma (HCC) recurrence within Milan criteria (MC). Little is known about outcomes for SLT in patients with recurrent HCC within University of California San Francisco (UCSF) criteria after liver resection (LR). METHODS: Between January 2001 and December 2011, 380 patients with HCC meeting UCSF criteria, 200 of which were resected (LR group) from a perspective of SLT in case of recurrence, and 180 directly underwent LT (PLT). We compared patient characteristics, perioperative and long-term outcomes between SLT and PLT groups. We also assessed the outcome of LR and PLT groups. RESULTS: Among the 200 patients in LR group, 86 (43%) developed HCC recurrence and 15/86 (17%) of these patients presented HCC recurrence outside UCSF criteria. Only 39 of the 86 patients underwent SLT, a transplantation rate of 45% of patients with HCC recurrence. Compared with PLT group, LR group showed lower overall survival rate (P = 0.005) and higher recurrence rate (P = 0.006). Although intraoperative blood loss and required blood transfusion were more frequent in SLT group, the perioperative mortality and posttransplant complications were similar in SLT and PLT groups. The overall survival and recurrence rates did not significantly differ between the two groups. When stratifying by graft type in the SLT group, overall survival and recurrence rates did not significantly differ between deceased donor LT (DDLT) and living donor LT (LDLT) groups. In the subgroup analysis by MC, similar results were observed between patients with recurrent HCC meeting MC and patients with recurrent HCC beyond MC but within UCSF criteria. CONCLUSION: Our single institution experience demonstrated that prior hepatectomy and SLT for recurrent HCC within UCSF criteria was feasible and SLT could achieve the same outcome as PLT.