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A deep understanding of two-phase displacement in porous media with permeability contrast is essential for the design and optimisation of enhanced oil recovery processes. In this paper, we investigate the forced imbibition behaviour in two dual-permeability geometries that are of equal permeability contrast. First, a mathematical model is developed for the imbibition in a pore doublet, which shows that the imbibition dynamics can be fully described by the viscosity ratio$\\lambda$and capillary number$Ca_m$which creatively incorporates the influence of channel width and length. Through the finite difference solution of the mathematical model, a$\\lambda$–$Ca_m$phase diagram is established to characterise the imbibition preference in the pore doublet. We then investigate the imbibition process in a dual-permeability pore network using a well-established lattice Boltzmann method, focusing on the competition between the viscous and capillary forces. Like in the pore doublet, the preferential imbibition occurs in high-permeability zone at high$Ca_{m}$but in low-permeability zone at low$Ca_{m}$. When$Ca_m$is not sufficiently high, an oblique advancing pattern is observed which is attributed to non-trivial interfacial tension. Using the newly defined capillary number, the critical$Ca_{m}$curve on which the breakthrough simultaneously occurs in both permeability zones is found to match well with that from the pore doublet and it is the optimal condition for maximising the imbibition efficiency in the entire pore network.

Prohibiting deep oxidation remains a challenging task in oxidative dehydrogenation of light alkane since the targeted alkene is more reactive than parent substrate. Here we tailor dual active sites to isolate dehydrogenation and oxidation instead of homogeneously active sites responsible for these two steps leading to consecutive oxidation of alkene. The introduction of HY zeolite with acid sites, three-dimensional pore structure and supercages gives rise to Ni 2+ Lewis acid sites (LAS) and NiO nanoclusters confined in framework wherein catalytic dehydrogenation of ethane occurs on Ni 2+ LAS resulting in the formation of ethene and hydrogen while NiO nanoclusters with decreased oxygen reactivity are responsible for selective oxidation of hydrogen rather than over-oxidizing ethene. Such tailored strategy achieves near 100% ethene selectivity and constitutes a promising basis for highly selective oxidation catalysis beyond oxidative dehydrogenation of light alkane. It is important but challenging to prohibit deep oxidation of alkene in oxidative dehydrogenation of light alkane. Here, dual active sites are tailored to isolate dehydrogenation and oxidation thus achieving superior ethene selectivity.

Continuous evolution of Omicron has led to a rapid and simultaneous emergence of numerous variants that display growth advantages over BA.5 (ref. 1 ). Despite their divergent evolutionary courses, mutations on their receptor-binding domain (RBD) converge on several hotspots. The driving force and destination of such sudden convergent evolution and its effect on humoral immunity remain unclear. Here we demonstrate that these convergent mutations can cause evasion of neutralizing antibody drugs and convalescent plasma, including those from BA.5 breakthrough infection, while maintaining sufficient ACE2-binding capability. BQ.1.1.10 (BQ.1.1 + Y144del), BA.4.6.3, XBB and CH.1.1 are the most antibody-evasive strains tested. To delineate the origin of the convergent evolution, we determined the escape mutation profiles and neutralization activity of monoclonal antibodies isolated from individuals who had BA.2 and BA.5 breakthrough infections 2 , 3 . Owing to humoral immune imprinting, BA.2 and especially BA.5 breakthrough infection reduced the diversity of the neutralizing antibody binding sites and increased proportions of non-neutralizing antibody clones, which, in turn, focused humoral immune pressure and promoted convergent evolution in the RBD. Moreover, we show that the convergent RBD mutations could be accurately inferred by deep mutational scanning profiles 4 , 5 , and the evolution trends of BA.2.75 and BA.5 subvariants could be well foreseen through constructed convergent pseudovirus mutants. These results suggest that current herd immunity and BA.5 vaccine boosters may not efficiently prevent the infection of Omicron convergent variants. Convergent mutations in hotspots of the SARS-CoV-2 Omicron receptor-binding domain can cause immune evasion and maintain sufficient ACE2-binding capability.

The continuing emergence of SARS-CoV-2 variants highlights the need to update COVID-19 vaccine compositions. However, immune imprinting induced by vaccination based on the ancestral (hereafter referred to as WT) strain would compromise the antibody response to Omicron-based boosters 1 – 5 . Vaccination strategies to counter immune imprinting are critically needed. Here we investigated the degree and dynamics of immune imprinting in mouse models and human cohorts, especially focusing on the role of repeated Omicron stimulation. In mice, the efficacy of single Omicron boosting is heavily limited when using variants that are antigenically distinct from WT—such as the XBB variant—and this concerning situation could be mitigated by a second Omicron booster. Similarly, in humans, repeated Omicron infections could alleviate WT vaccination-induced immune imprinting and generate broad neutralization responses in both plasma and nasal mucosa. Notably, deep mutational scanning-based epitope characterization of 781 receptor-binding domain (RBD)-targeting monoclonal antibodies isolated from repeated Omicron infection revealed that double Omicron exposure could induce a large proportion of matured Omicron-specific antibodies that have distinct RBD epitopes to WT-induced antibodies. Consequently, immune imprinting was largely mitigated, and the bias towards non-neutralizing epitopes observed in single Omicron exposures was restored. On the basis of the deep mutational scanning profiles, we identified evolution hotspots of XBB.1.5 RBD and demonstrated that these mutations could further boost the immune-evasion capability of XBB.1.5 while maintaining high ACE2-binding affinity. Our findings suggest that the WT component should be abandoned when updating COVID-19 vaccines, and individuals without prior Omicron exposure should receive two updated vaccine boosters. Exposure to early variants of SARS-CoV-2 results in immune imprinting in mouse models and in humans, reducing neutralizing antibody titres against Omicron variants, which could be mitigated with multiple updated boosters.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages BA.2.12.1, BA.4 and BA.5 exhibit higher transmissibility than the BA.2 lineage 1 . The receptor binding and immune-evasion capability of these recently emerged variants require immediate investigation. Here, coupled with structural comparisons of the spike proteins, we show that BA.2.12.1, BA.4 and BA.5 (BA.4 and BA.5 are hereafter referred collectively to as BA.4/BA.5) exhibit similar binding affinities to BA.2 for the angiotensin-converting enzyme 2 (ACE2) receptor. Of note, BA.2.12.1 and BA.4/BA.5 display increased evasion of neutralizing antibodies compared with BA.2 against plasma from triple-vaccinated individuals or from individuals who developed a BA.1 infection after vaccination. To delineate the underlying antibody-evasion mechanism, we determined the escape mutation profiles 2 , epitope distribution 3 and Omicron-neutralization efficiency of 1,640 neutralizing antibodies directed against the receptor-binding domain of the viral spike protein, including 614 antibodies isolated from people who had recovered from BA.1 infection. BA.1 infection after vaccination predominantly recalls humoral immune memory directed against ancestral (hereafter referred to as wild-type (WT)) SARS-CoV-2 spike protein. The resulting elicited antibodies could neutralize both WT SARS-CoV-2 and BA.1 and are enriched on epitopes on spike that do not bind ACE2. However, most of these cross-reactive neutralizing antibodies are evaded by spike mutants L452Q, L452R and F486V. BA.1 infection can also induce new clones of BA.1-specific antibodies that potently neutralize BA.1. Nevertheless, these neutralizing antibodies are largely evaded by BA.2 and BA.4/BA.5 owing to D405N and F486V mutations, and react weakly to pre-Omicron variants, exhibiting narrow neutralization breadths. The therapeutic neutralizing antibodies bebtelovimab 4 and cilgavimab 5 can effectively neutralize BA.2.12.1 and BA.4/BA.5, whereas the S371F, D405N and R408S mutations undermine most broadly sarbecovirus-neutralizing antibodies. Together, our results indicate that Omicron may evolve mutations to evade the humoral immunity elicited by BA.1 infection, suggesting that BA.1-derived vaccine boosters may not achieve broad-spectrum protection against new Omicron variants. Biochemical and structural studies of the interactions between antibodies and spike proteins from SARS-CoV-2 Omicron subvariants indicate how these variants have evolved to escape antibody-mediated neutralization.

Small nucleolar RNA SNORD50A and SNORD50B (SNORD50A/B) has been reported to be recurrently deleted and function as a putative tumor suppressor in different types of cancer by binding to and suppressing the activity of the KRAS oncoproteins. Its deletion correlates with poorer patient survival. However, in this study, we surprisingly found that SNORD50A/B loss predicted a better survival in breast cancer patients carrying wild-type p53. Functional studies showed that SNORD50A/B deletion strongly inhibited the proliferation, migration, invasion and tumorigenic potential, and induced cell cycle arrest and apoptosis in p53 wild-type breast cancer cells, while exerted the opposite effects in p53 mutated breast cancer cells. This was also supported by ectopically expressing SNORD50A/B in both p53 wild-type and mutated breast cancer cells. Mechanistically, SNORD50A/B clearly enhances the interaction between E3 ubiquitin ligase TRIM21 and its substrate GMPS by forming a complex among them, thereby promoting GMPS ubiquitination and its subsequent cytoplasmic sequestration. SNORD50A/B deletion in p53 wild-type breast cancer cells will release GMPS and induce the translocation of GMPS into the nucleus, where GMPS can recruit USP7 and form a complex with p53, thereby decreasing p53 ubiquitination, stabilizing p53 proteins, and inhibiting malignant phenotypes of cancer cells. Altogether, the present study first reports that SNORD50A/B plays an oncogenic role in p53 wild-type breast cancers by mediating TRIM21-GMPS interaction.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of XBB lineages on the receptor-binding domain (RBD) L455F and F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, and HK.3. Here, we show that neutralizing antibody (NAb) evasion drives the convergent evolution of F456L, while the epistatic shift caused by F456L enables the subsequent convergence of L455F through ACE2 binding enhancement and further immune evasion. L455F and F456L evade RBD-targeting Class 1 public NAbs, reducing the neutralization efficacy of XBB breakthrough infection (BTI) and reinfection convalescent plasma. Importantly, L455F single substitution significantly dampens receptor binding; however, the combination of L455F and F456L forms an adjacent residue flipping, which leads to enhanced NAbs resistance and ACE2 binding affinity. The perturbed receptor-binding mode leads to the exceptional ACE2 binding and NAb evasion, as revealed by structural analyses. Our results indicate the evolution flexibility contributed by epistasis cannot be underestimated, and the evolution potential of SARS-CoV-2 RBD remains high.

Polyamines have been reported to be involved in grain filling and they might contribute to the construction of heat resistance of some cereals. In this study, the hybrid rice ‘YLY 689’ was used to explore the possible effects of exogenous spermidine (Spd) on seed quality under high temperature during the filling stage. Rice spikes were treated with Spd or its synthesis inhibitor cyclohexylamine (CHA) after pollination, and then the rice plants were transferred to 40 °C for 5-day heat treatment. The results showed that, compared with the control under high temperature, Spd pretreatment significantly improved the germination percentage, germination index, vigor index, seedling shoot height, and dry weight of seeds harvested at 35 days after pollination, while the CHA significantly decreased the seed germination and seedling growth. Meanwhile, Spd significantly increased the peroxidase (POD) activity and decreased the malondialdehyde (MDA) content in seeds. In addition, after spraying with Spd, the endogenous content of spermidine and spermine and the expression of their synthetic genes, spermidine synthase (SPDSYN) and spermine synthase (SPMS1 and SPMS2), significantly increased, whereas the accumulation of amylose and total starch and the expression of their related synthase genes, soluble starch synthase II-3 (SS II-3) and granules bound starch synthase I (GBSSI), also increased to some extent. The data suggests that exogenous Spd pretreatment could alleviate the negative impacts of high temperature stress on rice seed grain filling and improve the rice seed quality to some extent, which might be partly caused by up-regulating endogenous polyamines and starch metabolism.

Transition metal carbide shows excellent performance in selective hydrogenation of acetylene, however, the carburization of Pd-based intermetallic compounds remains infeasible. Here we report the successful synthesis of an unprecedented Pd 3 ZnC x intermetallic carbide, via co-infiltration of zinc and carbon in one-step carburization by syngas. Utilizing state-of-the-art in situ characterizations and theoretical calculation, we unveil the dynamic evolution of Pd 3 ZnC x during carburization, forming a Pd 3 Zn like cubic phase carbide structure. A unique transitional state (Pd t ) with low content of Zn/C co-infiltration is clearly identified facilitating phase transition and sustain incorporation of carbon and zinc at elevated temperatures. The Pd 3 ZnC x carbide shows by far the best catalytic performance in the selective hydrogenation of acetylene with a high selectivity (>90%) even at a high H 2 /C 2 H 2 ratio. Our results therefore provide a co-infiltration strategy and dynamic insights for the one-step synthesis of Pd based intermetallic carbides, towards high-performance intermetallic compound for selective hydrogenation of acetylene. Transition metal carbides exhibit outstanding performance in the selective hydrogenation of acetylene, but carburizing Pd-based intermetallic compounds has been challenging. Here, the authors present a successful synthesis of Pd 3 ZnC x intermetallic carbide for selective hydrogenation of acetylene through a one-step co-infiltration of zinc and carbon using syngas.

Background C-X-C motif chemokine ligand 10 (CXCL10) is implicated in HIV-associated neuroinflammation, yet its association with HIV-associated neurocognitive disorders (HAND) remains unclear. We conducted a meta-analysis to evaluate cerebrospinal fluid (CSF) CXCL10 differences between people living with HIV (PLWH) with and without HAND and to assess the odds of HAND in relation to high versus low CSF CXCL10 levels. Methods PubMed, Embase, and Web of Science were systematically searched. Observational studies reporting CSF CXCL10 levels in adult PLWH with and without HAND were included. Standardized mean difference (SMD) and odds ratio (OR) were pooled using random-effects models accounting for the potential influence of heterogeneity. Results Eleven studies involving 1,536 PLWH were included. Compared to those without HAND, PLWH with HAND had significantly higher CSF CXCL10 levels (SMD: 0.56, 95% CI: 0.17–0.96; p  < 0.001), with high heterogeneity (I² = 86% and τ² = 0.31). The 95% prediction interval (PI: − 0.78 to 1.91) indicated substantial between-study variability. Subgroup analyses showed significantly greater CXCL10 elevation in studies with ≤ 50% ART coverage (SMD: 0.90 vs. 0.17; p  = 0.04) and in those evaluating HIV-associated dementia (SMD: 1.45 vs. 0.37; p  < 0.001). Meta-regression did not identify any statistically significant moderators, although ART proportion and CD4 + count explained 29.2% and 25.6% of the variance, respectively. No significant association was found between high CSF CXCL10 and HAND (OR: 1.41, 95% CI: 0.90–2.22; p  = 0.13). Conclusion Elevated CSF CXCL10 may be associated with HAND in PLWH, particularly among ART-naïve individuals and in more severe cognitive impairment. However, substantial heterogeneity and a wide PI suggest that the strength of this association varies across populations. CSF CXCL10 remains a promising but not definitive biomarker for HAND risk stratification.