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摘要： Balancing the energy and stability is a key challenge in the design of energetic materials. In this work, a series of novel compounds were synthesized by introducing varying numbers of nitro groups through precise modifications to the 1,2,4-triazole skeleton. Comparative studies demonstrated that tuning nitro groups in metastable structural moieties optimized the oxygen balance and enhanced stability while maintaining favorable detonation performance. Specifically, compound N-(5-nitro-3-(trinitromethyl)-1,2,4-triazol-1-yl)­nitramide (NT-2) was obtained as solvent-free single crystals with a high density of 1.92 g cm^–3 through a regioisomeric approach. Compound 3-(dinitromethyl)-5-nitro-1,2,4-triazol-1-amine (NT-7) possesses a high thermal decomposition temperature of 179 °C and low mechanical sensitivity (FS = 128 N and IS = 23 J). Its detonation performance (V _D = 8990 m s^–1 and P = 35.6 GPa) is superior to that of RDX. Ignition experiments revealed that the type and number of nitro groups significantly affect the ignition behavior. Furthermore, a novel hydrolysis route was developed for the preparation of FOX-7 from gem-dinitro-substituted 1,2,4-triazole. This work could provide new insights into the energetic performance and structural design of energetic materials.

关键词： PD-1 resistance   colorectal cancer   MSI-H   DNA mismatch repair   MSH2   MSH6  

关键词： immune checkpoint inhibitor   non-small cell lung cancer   pembrolizumab   atezolizumab   real-world data  

摘要： Background: Immune checkpoint inhibitor monotherapy targeting the PD-1/PD-L1 axis is a standard first-line treatment option for patients with metastatic non-small cell lung cancer (NSCLC) and high PD-L1 expression. However, comparative real-world data evaluating PD-1 versus PD-L1 inhibitor monotherapy in this population remain limited. Methods: We conducted a retrospective, single-center real-world analysis of patients with metastatic NSCLC and high PD-L1 expression who initiated first-line immune checkpoint inhibitor monotherapy between May 2024 and January 2025. Patients were treated with either pembrolizumab (PD-1 inhibitor) or atezolizumab (PD-L1 inhibitor) as monotherapy. Progression-free survival (PFS) was estimated using the Kaplan-Meier method and compared using the log-rank test. Univariable and multivariable Cox proportional hazards regression models were applied to identify clinical factors associated with PFS. Results: A total of 125 patients were included, of whom 73 received pembrolizumab and 52 received atezolizumab. The median PFS was numerically longer in patients treated with pembrolizumab compared with atezolizumab (9.93 vs. 5.33 months), although this difference did not reach statistical significance (HR 1.14, 95% CI 0.74-1.74;p = 0.559). Poor performance status (ECOG PS 2) was independently associated with inferior PFS (HR 3.22, 95% CI 2.02-5.12), whereas very high PD-L1 expression (TPS 90-100%) was independently associated with improved PFS (HR 0.57, 95% CI 0.35-0.93). Conclusions: In this real-world cohort, pembrolizumab was associated with numerically longer PFS than atezolizumab;however, this difference was not statistically significant. Outcomes were primarily driven by baseline clinical factors, particularly performance status and the degree of PD-L1 expression. Larger cohorts with longer follow-up are warranted to clarify potential differences and assess long-term outcomes.

摘要： Type I interferons restrict HIV-1 replication by inducing antiviral genes, but the full spectrum of their effectors remains incompletely defined. Here we identify ZFP36L2, a nuclear RNA-binding protein, as an IFN-β-induced inhibitor of HIV-1 infection. Silencing ofZFP36L2impairs IFN-β-mediated HIV-1 inhibition, whereas overexpression of ZFP36L2 suppresses viral replication. Notably, reconstitution of ZFP36L2 in CD4⁺ T cells from HIV-1-infected individuals reduces viral spread ex vivo, and ZFP36L2 transcript levels inversely correlate with plasma viral loads in vivo. Mechanistically, ZFP36L2 binds to the HIV-1 Rev protein and inhibits the nuclear export of Rev response element-containing viral transcripts, thereby blocking downstream viral protein expression. A Rev mutant lacking amino acids 109–116 fails to bind ZFP36L2 and exhibits resistance to ZFP36L2-mediated inhibition, underscoring the functional significance of this interaction. These findings establish ZFP36L2 as an IFN-β-induced antiviral factor that suppresses HIV-1 replication through Rev-dependent inhibition of viral RNA export.