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The plasma membrane is enriched for receptors and signaling proteins that are accessible from the extracellular space for pharmacological intervention. Here we conducted a series of CRISPR screens using human cell surface proteome and integrin family libraries in multiple cancer models. Our results identified ITGAV (integrin αV) and its heterodimer partner ITGB5 (integrin β5) as the essential integrin α/β pair for cancer cell expansion. High-density CRISPR gene tiling further pinpointed the integral pocket within the β-propeller domain of ITGAV for integrin αVβ5 dimerization. Combined with in silico compound docking, we developed a CRISPR-Tiling-Instructed Computer-Aided (CRISPR-TICA) pipeline for drug discovery and identified Cpd_AV2 as a lead inhibitor targeting the β-propeller central pocket of ITGAV. Cpd_AV2 treatment led to rapid uncoupling of integrin αVβ5 and cellular apoptosis, providing a unique class of therapeutic action that eliminates the integrin signaling via heterodimer dissociation. We also foresee the CRISPR-TICA approach to be an accessible method for future drug discovery studies.

Objective To assess global, regional and national trends in the impact of floods from 1990 to 2022 and determine factors influencing flood-related deaths. Methods We used data on flood disasters from the International Disaster Database for 1990-2022 from 168 countries. We calculated the annual percentage change to estimate trends in the rates of people affected and killed by floods by study period, World Health Organization (WHO) region, country income level and flood type. We used multivariable logistic regression analysis to assess the factors associated with death from floods. Findings From 1990 to 2022, 4713 floods were recorded in 168 countries, which affected > 3.2 billion people, caused 218 353 deaths and were responsible for more than 1.3 trillion United States dollars of economic losses. The WHO Western Pacific Region had the most people affected by floods (> 2.0 billion), accounting for 63.19% (2 024 599 380/3 203 944 965) of all affected populations. The South-East Asia Region had the most deaths (71 713, 32.84%). The African and Eastern Mediterranean Regions had the highest number of people affected and killed by floods per 100 000 population in 2022. The odds of floods causing more than 50 deaths were significantly higher in low-income countries (adjusted odds ratio: 14.34; 95% confidence interval: 7.46 to 30.04) compared with high-income countries. Numbers of people affected and mortality due to floods declined over time. Conclusion Despite the decreases in populations affected and deaths, floods still have a serious impact on people and economies globally, particularly in lower-income countries. Action is needed to improve disaster risk management and flood mitigation. Objectif Evaluer les tendances mondiales, regionales et nationales relatives a l'impact des inondations entre 1990 et 2022, mais aussi determiner les facteurs influengant les deces causes par ces inondations. Methodes Nous avons exploite les donnees concernant 168 pays et reprises dans la base de donnees internationale sur les catastrophes pour la periode allant de 1990 a 2022. Nous avons ensuite calcule la variation annuelle en pourcentage afin de degager des tendances quant au nombre de personnes touchees, voire tuees par des inondations en fonction de la periode d'etude, de la region telle que definie par l'Organisation mondiale de la Sante (OMS), du niveau de revenu du pays et du type d'inondation. Enfin, nous avons employe une analyse multivariee de regression logistique pour determiner les facteurs associes aux deces en cas d'inondations. Resultats Entre 1990 et 2022, 4713 inondations ont ete recensees dans 168 pays. Elles ont touche plus de 3,2 milliards de personnes, cause 218 353 morts et entraine des pertes economiques superieures a 1,3 billion de dollars americains. La region du Pacifique occidental de l'OMS est celle ou le plus grand nombre d'habitants ont ete affectes par ces phenomenes (> 2 milliards), representant 63,19% (2 024 599 380 / 3 203 944 965) de l'ensemble des populations impactees. C'est la region d'Asie du Sud-Est qui comptait le plus grand nombre de deces (71 713, soit 32,84%). La region Africaine et la region de la Mediterranee orientale denombraient toutes deux la plus grande proportion de personnes touchees et tuees lors d'inondations par 100 000 habitants en 2022. La probability que les inondations soient a l'origine de plus de 50 morts etait nettement plus importante dans les pays a revenu faible (odds ratio ajuste : 14,34; intervalle de confiance a 95% : 7,46 a 30,04) que dans les pays a revenu eleve. Letendue des repercussions et le taux de mortalite des inondations diminuaient au fil du temps. Conclusion Malgre une baisse du nombre de personnes touchees et tuees, les inondations continuent a avoir un impact considerable sur les populations et les economies a travers le monde, surtout dans les pays aux revenus plus faibles. Des actions sont requises pour ameliorer la gestion des risques de catastrophes et la lutte contre les inondations. Objetivo Evaluar las tendencias mundiales, regionales y nacionales del impacto de las inundaciones de 1990 a 2022 y determinar los factores que influyen en las muertes relacionadas con las inundaciones. Metodos Se utilizaron datos sobre catastrofes por inundaciones de la Base de Datos Internacional sobre catastrofes para 1990-2022 de 168 paises. Se calculo la variacion porcentual anual para estimar las tendencias de las tasas de personas afectadas y fallecidas por inundaciones segun el periodo de estudio, la region de la Organizacion Mundial de la Salud (OMS), el nivel de ingresos del pais y el tipo de inundacion. Se utilizo un analisis de regresion logistica multivariable para evaluar los factores asociados a la muerte por inundaciones. Resultados Entre 1990 y 2022, se registraron 4713 inundaciones en 168 paises, que afectaron a >3200 millones de personas, causaron 218 353 muertes y fueron responsables de mas de 1,3 billones de dolares estadounidenses de perdidas economicas. La Region del Pacifico Occidental de la OMS fue la mas afectada por las inundaciones (>2000 millones), con un 63,19% (2 024 599 380/3 203 944 965) de todas las poblaciones afectadas. La Region de Asia Sudoriental fue la que registro mas muertes (71 713, 32,84%). Las regiones de Africa y el Mediterraneo Oriental registraron el mayor numero de personas afectadas y fallecidas por inundaciones por cada 100 000 habitantes en 2022. Las probabilidades de que las inundaciones causaran mas de 50 muertes fueron significativamente mayores en los paises de ingresos bajos (razon de probabilidades ajustada: 14,34; intervalo de confianza del 95%: 7,46 a 30,04) en comparacion con los paises de ingresos altos. El numero de personas afectadas y la mortalidad por inundaciones disminuyeron con el tiempo. Conclusion A pesar de la disminucion de las poblaciones afectadas y de las muertes, las inundaciones siguen teniendo un grave impacto en las personas y las economias de todo el mundo, en especial en los paises con ingresos mas bajos. Es preciso actuar para mejorar la gestion del riesgo de catastrofes y la mitigacion de las inundaciones. [phrase omitted], Introduction Natural disasters are catastrophic events of atmospheric, geological and hydrological origins. These disasters include earthquakes, floods, volcanic eruptions, landslides, tsunamis and droughts. (1) From 1998 to 2017, 1.3 million [...]

In order to identify the pathogen that caused rust of Bletilla striata in Guangxi Zhuang Autonomous Region and to screen resistance resources for B. striata, the rust pathogen was isolated from infected leaves of B. striata and identified using morphology and molecular methods. At the same time, the resistance of 23 B. striata from different regions was evaluated by artificial inoculation of pathogen. The results were as follows: (1) The urediopores of strain X2 isolated from diseased leaves in B. striata were golden yellow, oval, (21.43-30.95) μm × (13.10-19.05) μm. The teleutospores were golden yellow, obovate or clavate, (17.25-30) μm × (5.5-6.65) μm. (2) The length of ITS sequence of strain X2(OQ826009) was 689 bp, which were compared with other ITS sequences in the GenBank, and the similarity reached 95.86% compared with Coleosporium sp. (KY783686.1). But the phylogenetic tree showed that the sequence was clustered together with two sequences of Coleosporium bletiae (MN108161.1, OP363680.1). The strain X2 was identified as Coleosporium bletiae by combining morphology and molecular methods. (3) After 14 days of artificial inoculation with strain X2, the disease index of 23 Bletilla striata ranged from 0 to 70.7. And the resistance of strain X2 from 23 B. striata were divided into six different levels according to the disease index. Among them, one immune materials was identified for the disease index was 0. Four highly resistant materials were identified for the disease index was 1.7-4.7. Six disease-resistant materials were identified for the disease index was 5.6-9.4. Five medium-resistant materials were identified for the disease index was 12.7-18.3. Five susceptible materials were identified for the disease index was 32.0-49.1 and two highly susceptible materials were identified for the disease index was 62.2-70.7. In conclusion, five materials (one immune material and four highly resistant materials) of B. striata from different places (Honghe City in Yunnan Province, Gongcheng County and Baise City in Guangxi Zhuang Autonomous Region, Zunyi City in Guizhou Province and Yichang City in Hubei Province, respectively) can be promoted directly or applied as parent materials for creating excellent germplasm to resist the rust in B. striata for they express immune or highly resistance. This study provides the basis for further research on pathogenesis and control of rust in B. striata.