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Background Patients with gastrointestinal cancer have a higher risk of malnutrition and postoperative infection. Objective To investigate the nutritional status of patients with gastrointestinal cancers and factors for postoperative infections. Method Based on the nutritional risk status, 294 patients with gastrointestinal tumours were divided into a nutritional risk group and a non-nutritional risk group, and the differences between the two groups were compared. Results Among the included patients, 128 were at preoperative nutritional risk (43.54%); there were significant differences between the two groups in terms of age (66.25 ± 11.73 vs. 58.36 ± 10.41 years, P  < 0.001), percentage of gastric cancers (39.84% vs. 28.92%, P  = 0.049), percentage of stage IV tumours (60.16% vs. 45.18%, P  = 0.011), total protein (64.90 ± 6.82 vs. 67.21 ± 7.41 g/L, P  = 0.007), albumin (38.32 ± 4.74 vs. 41.61 ± 5.10 g/L, P  < 0.001) and haemoglobin (112.72 ± 22.63 vs. 125.11 ± 22.79 g/L, P  < 0.001). Multivariate logistic regression analysis showed that risk factors for postoperative infections in patients included age ≥ 60 years (odds ratio [OR] = 2.266 95%CI = 1.357–4.134), Nutrition Risk Screening (NRS)-2002 score ≥ 3 (OR = 2.183, 95%CI = 1.218–4.102), alcohol history (OR = 2.505, 95%CI = 1.370–4.683), comorbid diabetes mellitus (OR = 2.110, 95%CI = 1.381–4.023) and surgical time ≥ 6 h (OR = 2.446, 95%CI = 1.359–4.758). Conclusion Patients with gastrointestinal cancers are at high incidence of preoperative nutritional risk, and those with an NRS-2002 score of > 3, history of alcohol consumption and surgical time of > 6 h have a higher risk of postoperative infections.

The development of an effective AIDS vaccine has been challenging because of viral genetic diversity and the difficulty of generating broadly neutralizing antibodies (bnAbs). We engineered trispecific antibodies (Abs) that allow a single molecule to interact with three independent HIV-1 envelope determinants: the CD4 binding site, the membrane-proximal external region (MPER), and the V1V2 glycan site. Trispecific Abs exhibited higher potency and breadth than any previously described single bnAb, showed pharmacokinetics similar to those of human bnAbs, and conferred complete immunity against a mixture of simian-human immunodeficiency viruses (SHIVs) in nonhuman primates, in contrast to single bnAbs. Trispecific Abs thus constitute a platform to engage multiple therapeutic targets through a single protein, and they may be applicable for treatment of diverse diseases, including infections, cancer, and autoimmunity.

During HIV-1 infection, antibodies are generated against the region of the viral gp120 envelope glycoprotein that binds CD4, the primary receptor for HIV-1. Among these antibodies, VRC01 achieves broad neutralization of diverse viral strains. We determined the crystal structure of VRC01 in complex with a human immunodeficiency virus HIV-1 gp120 core. VRC01 partially mimics CD4 interaction with gp120. A shift from the CD4-defined orientation, however, focuses VRC01 onto the vulnerable site of initial CD4 attachment, allowing it to overcome the glycan and conformational masking that diminishes the neutralization potency of most CD4-binding-site antibodies. To achieve this recognition, VRC01 contacts gp120 mainly through immunoglobulin V-gene regions substantially altered from their genomic precursors. Partial receptor mimicry and extensive affinity maturation thus facilitate neutralization of HIV-1 by natural human antibodies.

Isatuximab is a monoclonal antibody targeting the transmembrane receptor and ectoenzyme CD38, a protein highly expressed on hematological malignant cells, including those in multiple myeloma (MM). Upon binding to CD38-expressing MM cells, isatuximab is thought to induce tumor cell killing via fragment crystallizable (Fc)-dependent mechanisms, including antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP), and complement-dependent cytotoxicity (CDC), as well as via direct Fc-independent mechanisms. Here, these mechanisms of action were investigated in MM and diffuse large B-cell lymphoma (DLBCL) cell lines, as well as in peripheral blood mononuclear cells derived from healthy donors, and in MM patient-derived samples. Our findings show that isatuximab-mediated cytotoxicity occurred primarily via ADCC and ADCP in MM cell lines and via ADCC and apoptosis in DLBCL cell lines expressing high levels of CD38. We identified the programmed cell death-1/programmed cell death-ligand 1 (PD-1/PD-L1) pathway and MM cell-secreted transforming growth factor-beta (TGF-β) as tumor cell-related features that could suppress CD38-mediated ADCC. Furthermore, we established that isatuximab can directly activate natural killer (NK) cells and promote NK cell-mediated cytotoxicity via crosslinking of CD38 and CD16. Finally, isatuximab-induced CDC was observed in cell lines with high CD38 receptor density (>250,000 molecules/cell) and limited expression of inhibitory complement regulatory proteins (CD46, CD55, and CD59; <50,000 molecules/cell). Taken together, our findings highlight mechanistic insights for isatuximab and provide support for a range of combination therapy approaches that could be tested for isatuximab in the future.

Cross-reactive neutralizing antibodies (NAbs) are found in the sera of many HIV-1-infected individuals, but the virologic basis of their neutralization remains poorly understood. We used knowledge of HIV-1 envelope structure to develop antigenically resurfaced glycoproteins specific for the structurally conserved site of initial CD4 receptor binding. These probes were used to identify sera with NAbs to the CD4-binding site (CD4bs) and to isolate individual B cells from such an HIV-1-infected donor. By expressing immunoglobulin genes from individual cells, we identified three monoclonal antibodies, including a pair of somatic variants that neutralized over 90% of circulating HIV-1 isolates. Exceptionally broad HIV-1 neutralization can be achieved with individual antibodies targeted to the functionally conserved CD4bs of glycoprotein 120, an important insight for future HIV-1 vaccine design.

Whether the effect of migration-selection-drift equilibrium on population structure is governed by spatial or environmental differences is usually elucidated by isolation-by-distance (IBD), isolation-by-environment (IBE), and isolation-by-resistance (IBR) tests. The population structure of Ammopiptanthus mongolicus , a broad-leaved evergreen psammophyte in eastern Central Asia, was previously thought to follow an isolation by distance pattern. However, recent studies have emphasized the effects of environmental factors on its growth and distribution, suggesting an important influence of local adaptation on the genetic structure of the species. Using inter-simple sequence repeat (ISSR) markers, we verified the previously inferred low intra-population variation and high inter-population differentiation. However, in contrast to previous studies, the results of partial Mantel tests and a maximum likelihood population effects mixed model (MLPE) suggested that local climate differences, rather than geographic distances or resistance distances, are the main factor affecting population differentiation. Further analysis with removal of multicollinear climatic variables and univariate MLPE found that summer and winter precipitation were crucial for shaping the current population genetic structure. Since local precipitation is related to the regeneration, colonization, and overwintering survival of A. mongolicus , its influence on demographic change may explain its effect on the population genetic structure. In addition, precipitation is related to terrain despite westward decreases, which explains the independence of genetic difference and geographic distance. The identified role of IBE suggests that collecting germplasm resources from genetically differentiated populations could be a more effective strategy to preserve the overall genetic diversity of the species than the establishment of corridors to enhance gene flow among populations.

In the RV144 HIV-1 vaccine efficacy trial, IgG antibody (Ab) binding levels to variable regions 1 and 2 (V1V2) of the HIV-1 envelope glycoprotein gp120 were an inverse correlate of risk of HIV-1 infection. To determine if V1V2-specific Abs cross-react with V1V2 from different HIV-1 subtypes, if the nature of the V1V2 antigen used to asses cross-reactivity influenced infection risk, and to identify immune assays for upcoming HIV-1 vaccine efficacy trials, new V1V2-scaffold antigens were designed and tested. Protein scaffold antigens carrying the V1V2 regions from HIV-1 subtypes A, B, C, D or CRF01_AE were assayed in pilot studies, and six were selected to assess cross-reactive Abs in the plasma from the original RV144 case-control cohort (41 infected vaccinees, 205 frequency-matched uninfected vaccinees, and 40 placebo recipients) using ELISA and a binding Ab multiplex assay. IgG levels to these antigens were assessed as correlates of risk in vaccine recipients using weighted logistic regression models. Levels of Abs reactive with subtype A, B, C and CRF01_AE V1V2-scaffold antigens were all significant inverse correlates of risk (p-values of 0.0008-0.05; estimated odds ratios of 0.53-0.68 per 1 standard deviation increase). Thus, levels of vaccine-induced IgG Abs recognizing V1V2 regions from multiple HIV-1 subtypes, and presented on different scaffolds, constitute inverse correlates of risk for HIV-1 infection in the RV144 vaccine trial. The V1V2 antigens provide a link between RV144 and upcoming HIV-1 vaccine trials, and identify reagents and methods for evaluating V1V2 Abs as possible correlates of protection against HIV-1 infection. ClinicalTrials.gov NCT00223080.

The power conversion efficiency (PCE) of perovskite solar cells (PSCs) is sufficiently high for commercialization, however, the long‐term stabilities of PSCs and potential Pb leakage need to be addressed seriously. Self‐healing PSCs are very promising for developing long‐life and flexible devices. Herein, we provide a review on self‐healing PSCs and aim to contribute a valuable summary and support to the ongoing efforts devoted to this area. In the first part, the major factors affecting the stabilities of PSCs and the corresponding stability‐losing mechanisms are briefly introduced, which is the groundwork for developing self‐healing PSCs. The second part is a brief introduction on self‐healing materials, including the key requirements, self‐healing mechanisms, and the typical applications in soft electronics. With the information in the first two parts, we conduct a comprehensive review on the research of self‐healing PSCs in the third part. Last but not least, the main challenges and long‐term perspective for realizing the large scale utilizations of self‐healing PSCs are discussed. In addition to the fields of PSCs, self‐healing strategies are applicable to other flexible (opto)electronics as well. Therefore, a broad readership from varied areas of soft devices can also find interested points from this review. The self‐healing strategy is very promising for addressing the long‐term stabilities and potential Pb leakage of perovskite solar cells (PSCs). Here, we provide a comprehensive review on the research of self‐healing PSCs. The main challenges and long‐term perspective of this area are also discussed. Besides self‐healing PSCs, a broad readership from other soft electronics can find interested points as well.

The objective of this study is to quantify the clinical accuracy of the Cyberknife Xsight Lung Tracking System (XLTS) in our center and calculate the PTV margin of XLTS treated lung tumors. Data from the treatment log files of 22 lung cancer patients treated with the CyberKnife XLTS were analyzed and the PTV margin was calculated. Segmentation, deformation, correlation, prediction and targeting errors were calculated from the log files of XLTS treatments. Two different methods were used to calculate anisotropic treatment margin. The relationships between tumor motion ranges and the correlation and prediction errors were also analyzed. Based on our estimation of a 4 mm global margin, 95% coverage in the S-I direction and 100% coverage in the L-R and A-P directions were obtained. Strong correlations between tumor motion range and the standard deviation (SD) of correlation and prediction errors were also found. Tumor position motion caused by respiration can be compensated using the Xsight Lung Tracking System. We found total tracking errors to be less than 4 mm in all three directions. This result could provide a reference for the selection of PTV margin for treatment with the CyberKnife XLTS.

Life depends on energy-carrying molecules to power many sustaining processes. There is evidence that these molecules may predate the rise of life on Earth, but how and when these dependencies formed is unknown. The resurrection of ancient enzymes provides a unique tool to probe the enzyme’s function and usage of energy-carrying molecules, shedding light on their biochemical origins. Through experimental reconstruction, this research investigates the ancestral dependence of a nitrogen-fixing enzyme on the energy carrier ATP, a requirement for function in the modern enzyme. We show that the resurrected ancestor does not have generalist nucleotide specificity. Rather, the ancestor has a strict requirement for ATP, like the modern enzyme, with similar function and efficiency. The findings elucidate the early-evolved necessity of energy-yielding molecules, delineating their role in ancient biochemical processes. Ultimately, these insights contribute to unraveling the intricate tapestry of evolutionary biology and the origins of life-sustaining dependencies.