T2T-YAO: A Telomere-to-telomere Assembled Diploid Reference Genome for Han Chinese.

Since its initial release in 2001, the human reference genome has undergone continuous improvement in quality, and the recently released telomere-to-telomere (T2T) version - T2T-CHM13 - reaches its highest level of continuity and accuracy after 20 years of effort by working on a simplified, nearly homozygous genome of a hydatidiform mole cell line. Here, to provide an authentic complete diploid human genome reference for the Han Chinese, the largest population in the world, we assembled the genome of a male Han Chinese individual, T2T-YAO, which includes T2T assemblies of all the 22 + X + M and 22 + Y chromosomes in both haploid. The quality of T2T-YAO is much better than all currently available diploid assemblies, and its haploid version, T2T-YAO-hp, generated by selecting the better assembly for each autosome, reaches the top quality of fewer than one error per 29.5 Mb, even higher than that of T2T-CHM13. Derived from an individual living in the aboriginal region of the Han population, T2T-YAO shows clear ancestry and potential genetic continuity from the ancient ancestors. Each haplotype of T2T-YAO possesses ∼ 330-Mb exclusive sequences, ∼ 3100 unique genes, and tens of thousands of nucleotide and structural variations as compared with CHM13, highlighting the necessity of a population-stratified reference genome. The construction of T2T-YAO, a truly accurate and authentic representative of the Chinese population, would enable precise delineation of genomic variations and advance our understandings in the hereditability of diseases and phenotypes, especially within the context of the unique variations of the Chinese population.

Corrigendum to "Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population".

[This corrects the article DOI: 10.34133/2022/9873831.].

A Self-Assembly ICG Nanoparticle Potentiating Targeted Photothermal and Photodynamic Therapy in NSCLC.

In nonsmall cell lung cancers (NSCLC), near-infrared (NIR) fluorescence imaging using indocyanine green (ICG) has proven to be an efficient approach for locating pulmonary nodules and pulmonary sentinel lymph nodes. However, due to a lack of tumor selectivity, ICG's use as a photosensitizer for photothermal therapy (PTT) and photodynamic therapy (PDT) is restricted. In the current study, we aimed to develop a type of high-performance NIR nanoparticle formulated with ICG to enhance its targeted efficacy and tumor specificity on NSCLC. An ICG-osimertinib nanoparticle (ICG-Osi) was self-assembled through π-π stacking, with a size of 276 nm and a surface charge of -7.4 mV. The NIR visibility and epidermal growth factor receptor (EGFR) targetability of the ICG-Osi was confirmed by its binding efficiency to EGFR-expressing NSCLC cells in vitro and in vivo, regardless of EGFR mutation status. The targeted effect was further confirmed in mouse xenograft models and showed an extended tumor retention time (>96 h). We demonstrated a significantly enhanced hyperthermia effect and a retained reactive oxygen species (ROS) generating ability of ICG-Osi, resulting in a 2-fold higher cell death rate than ICG alone. The ICG-Osi down-regulated GPX4 and p62 expression while up-regulating caspase-3 and beclin1 expression in NSCLC cells, indicating a complex network of cell death-related proteins. Considering the merits of simple assembly, EGFR binding efficacy, improved hyperthermia effect, and efficient cancer cell suppression, the ICG-Osi exhibits great potential for clinical application in EGFR-expressing NSCLC therapy.

Comprehensive Humoral and Cellular Immune Responses to SARS-CoV-2 Variants in Diverse Chinese Population.

The SARS-CoV-2 variants have been emerging and have made great challenges to current vaccine and pandemic control strategies. It is urgent to understand the current immune status of various Chinese populations given that the preexisting immunity has been established by national vaccination or exposure to past variants. Using sera from 85 individuals (including 21 convalescents of natural infection, 15 cases which suffered a breakthrough infection after being fully vaccinated, and 49 healthy vaccinees), we showed significantly enhanced neutralizing activities against SRAS-CoV-2 variants in convalescent sera, especially those who had been fully vaccinated. The neutralizing antibodies against Omicron were detectable in 75% of convalescents and 44.9% of healthy vaccinees (p = 0.006), with a GMT of 289.5, 180.9-463.3, and 42.6, 31.3-59, respectively. However, the neutralizing activities were weaker in young convalescents (aged < 18 y), with a detectable rate of 50% and a GMT of 46.4 against Omicron. We also examined and found no pan-sarbecovirus neutralizing activities in vaccinated SARS-CoV-1 survivors. A booster dose could further increase the breadth and magnitude of neutralization against WT and variants of concern (VOCs) to different degrees. In addition, we showed that COVID-19-inactivated vaccines can elicit Omicron-specific T-cell responses. The positive rates of ELISpot reactions were 26.7% (4/15) and 43.8% (7/16) in the full vaccination group and the booster vaccination group, respectively, although without statistically significant difference. The neutralizing antibody titers declined while T-cell responses remain consistent over 6 months. These findings will inform the optimization of public health vaccination and intervention strategies to protect diverse populations against SARS-CoV-2 variants. Advances. Breakthrough infection significantly boosted neutralizing activities against SARS-CoV-2 variants as compared to booster immunization with inactivated vaccine. Vaccine-induced virus-specific T-cell immunity, on the other hand, may compensate for the shortfall. Furthermore, the public health system should target the most vulnerable group due to a poorer protective serological response in both infected and vaccinated adolescents.

Comprehensive Risk Assessment of Typical High-Temperature Cities in Various Provinces in China.

Global climate change results in an increased risk of high urban temperatures, making it crucial to conduct a comprehensive assessment of the high-temperature risk of urban areas. Based on the data of 194 meteorological stations in China from 1986 to 2015 and statistical yearbooks and statistical bulletins from 2015, we used GIS technology and mathematical statistics to evaluate high-temperature spatial and temporal characteristics, high-temperature risk, and high-temperature vulnerability of 31 cities across China. Over the past 30 years, most Chinese cities experienced 5-8 significant oscillation cycles of high-temperature days. A 15-year interval analysis of high-temperature characteristics found that 87% of the cities had an average of 5.44 more high-temperature days in the 15-year period from 2001 to 2015 compared to the period from 1986 to 2000. We developed five high-temperature risk levels and six vulnerability levels. Against the background of a warming climate, we discuss risk mitigation strategies and the importance of early warning systems.

Follow-Ups on Persistent Symptoms and Pulmonary Function Among Post-Acute COVID-19 Patients: A Systematic Review and Meta-Analysis.

Objective: As the number of recovering COVID-19 patients increases worldwide, the persistence of symptoms and signs through the post-acute phase indicates an urgent need for prolonged follow-up care. To explore existing data about post-acute COVID-19 syndrome, this meta-analysis assesses the prevalence of persistent manifestations in multiple systems and abnormalities in lung function, as well as their related risks in patients with various severities. Methods: Articles about discharged COVID-19 patients (published from January 1, 2020 to February 23, 2021) were obtained by searching four databases. Cohort studies with follow-up periods >1 month post-discharge or >2 months post-admission were included. Results: A total of 4,478 COVID-19 patients from 16 cohort studies were included in this meta-analysis. Fatigue or weakness (47%) were the most prevalent physical effects of post-acute COVID-19 syndrome, while psychosocial (28%) symptoms were the most common manifestations among several systems. Abnormalities in lung function of recovering patients, i.e., DLCO <80% (47%, 95% CI: 32-61%) persisted for long periods. Severe patients were more likely to present joint pain (OR 1.84, 95% CI: 1.11-3.04) and decreased lung functions compared with non-severe patients, with pooled ORs for abnormal TLC, FEV1, FVC, and DLCO of 3.05 (95% CI: 1.88-4.96), 2.72 (95% CI: 1.31-5.63), 2.52 (95% CI: 1.28-4.98), and 1.82 (95% CI: 1.32-2.50), respectively. Conclusions: Our research indicates that patients recovering from COVID-19 manifest long-term, multi-system symptoms, and the adverse effects on psychosocial health and lung functions were the most extensive and persistent. These findings together may facilitate much needed in-depth study of clinical treatments for long-term, post-acute phase symptoms that affect a great number of recovering COVID-19 patients.