Pokharel, M. | Search bioRxiv

bioRxiv2026

HS3ST1 regulates pulmonary inflammation and is a determinant of clinical outcomes after trauma and hemorrhagic shock

Mechanisms that promote organ injury after trauma and hemorrhagic shock (T/HS) remain poorly defined. Endothelial heparan sulfates with a 3-O-sulfate (3-OS) modification, controlled by the HS3ST1 gene, have anticoagulant and anti-inflammatory properties through their interaction with antithrombin. Our objective was to determine whether HS3ST1 deficiency drives organ injury and poor outcomes after T/HS. Hs3st1-/- and wild-type (WT) mice were subjected to T/HS followed by resuscitation with lactated ringers (LR) or fresh frozen plasma (FFP). While no differences were observed between WT and Hs3st1-/- LR resuscitated mice, lung injury and leukocyte infiltrates were significantly increased in FFP resuscitated Hs3st1-/-compared to WT mice. In vitro, leukocyte slow rolling and adherence was increased in HS3ST1 KO compared to WT cells. Among 472 T/HS patients, of which 31 (7%) were homozygous for the rs16881446 variant allele (GG), the number of ventilator free days was lower, and mortality was significantly higher in AG and GG patients. The rs16881446 genotype was independently associated with mortality. In conclusion, HS3ST1 deficiency mitigates organ protection from FFP resuscitation, partly through mediating EC:leukocyte engagement, and predicts mortality after T/HS. These findings identify a novel therapeutic target and prognostic tool that can be leveraged towards improved risk stratification after trauma.

cell biology↗

bioRxiv2022

Human-sloth bear conflict in Nepal - case study from an unprotected Churia forest

Human-sloth bear conflict, generally in the form of human attacks, is common throughout most areas where sloth bears co-occur with humans. The situation is more prevalent in multi-use forest landscapes outside protected areas. Although sloth bears are a conflict-prone species in Nepal, there is a clear lack of systematic studies that can inform human safety and conflict mitigation. We used data from questionnaire-based interviews with conflict-affected people and witnesses to provide detailed information about human-sloth bear conflict (1990- 2021) in the Trijuga forest, an important sloth bear stronghold outside protected areas in Nepal. The data were analyzed using descriptive statistics, chi-square tests, and regression analysis. For the time period, 66 conflict incidents involving 69 human individuals were recorded, with an annual average of 2.06 (SD = 1.48) incidents and 1.75 (SD = 1.34) attacks. Conflicts primarily impacted working-age group (25-55 years old) men, whose primary occupation was farming and who frequented the forest regularly. They typically occurred between 0900 and 1500, inside forests, and in habitats associated with poor land cover visibility. Poor visibility was also a significant positive determinant of bear attacks on humans. Fifty-six conflict incidents resulted in attacks that injured 59 people, with a fatality rate of 8.47%. Victims of bear attacks frequently had serious injuries, especially to the head and neck areas of the body. Serious injuries were more likely to occur to lone individuals than to people who were in groups of two or more. We suggest identification of conflict-risk habitats through a participatory mapping approach and education programs for the local people for effective human-sloth bear conflict management in Nepals unprotected forests.

ecology↗