Objective To analyze gene expression profiles of biopsy specimens from breast cancer patients who were treated with neoadjuvant chemotherapy(NAC) after biopsies, and to identify the genes which are closely associated with the efficacy of neoadjuvant chemotherapy with T/FAC [docetaxel(Taxotere), 5-fluorouracil, doxorubicin and cyclophosphamide] or T/FEC (Taxotere, 5-fluorouracil, epirubicin and cyclophosphamide) regimen.Methods We retrieved and collected gene expression profiles from publicly available databases.Four datasets, a total of 844 samples, were finally retained because all the patients had received a uniform neoadjuvant chemotherapy regimen.Response to neoadjuvant chemotherapy was categorized as a pathological complete response (pCR) or residual invasive cancer (RD).The differentially expressed genes (adjusted P-value<0.05) and therapeutic efficacy were analyzed and explored.Results After differential analysis, genes whose expressions were higher or lower in pCR group than in RD group were identified in each of the four datasets, respectively.There were 34 and 42 genes which were simultaneously more highly expressed or more lowly expressed in pCR group than in RD group in the four datasets.The unsupervised clustering, based on the 76 intersection genes, showed that the pCR specimens tended to form one cluster and the RD tended to form the other.Conclusion The seventy-six differentially expressed genes are associated with the efficacy of neoadjuvant chemotherapy and are likely to be novel predictive biomarkers for the efficacy of neoadjuvant chemotherapy.

On the basis of pre-experiment research and the hypothesis of“amputated lumbricus”, this research was aimed to explore mechanism of active components of the amputated lumbricus to promote wound healing. Skin excision was used to establish the mice model. The amputated lumbricus extract was prepared. HE staining and immunohistochemistry techniques were used in the determination of the wound healing rate and changes of VEGF, bFGF, TGF-β1 expression during wound healing period. The results showed that compared with the blank control group, the healing rate of the amputated lumbricus extract group was better. And the HE staining showed better improvement of traumatic tissues. There was no statistic differences on the expression of VEGF and TGF-β1 between the amputated lumbricus extract group and the normal saline group (P> 0.05). The expression of bFGF in amputated lumbricus extract group reached peak earlier than the control group and also lasted a longer time. The amputated lumbricus extract group reached peak on the first day, which had a significant difference (P < 0.05) compared with the control group at the same timepoint. It was concluded that the external application of amputated lumbricus extract had wound healing effect on traumatic skin of mice. Its mechanism may be irrelevant to the expression of VEGF and TGF-β1. However, it may be related to the increasing of bFGF expression in the injured regions during the inflammation stage and proliferation stage.

Objective To identify the eye movement characteristics that can distinguish reading interest and comprehensibilityin order to provide reference for prediction of reading interest and comprehensibility based on eye movement.Methods Tobii Glasses 3 was used to collect eye tracking data from 11 participants who read 12 texts on different topics.After reading all the texts,the participants marked each sentence with theirlevels of interest and comprehensibility.Then,Python R and excel software were used to preprocess and analyze the data,and the differences in eye movementamid the four combinations of reading interest(interested or not)and comprehensibility(levels of difficulty)were studiedat overall and individual levels.Results At the overall level,there were statistically significant differences in eye movement between the easy comprehension group and the difficult comprehensiongroup where interest was concerned,but there was little difference between the interested group and the disinterested groupwhen it came to comprehensibility.There were differences in eye movement behavior between individuals,and some of the statistically significant differences in eye movement were consistent across most of the participants.In addition,some of the eye movement characteristicswere oppositeacross different individuals or could not distinguish between the interested and disinterested at the overall level,but could be distinguished within individuals.Conclusion At the overall level,it is relatively easy to determine comprehensibility through eye movement,but it is more difficult to distinguish whether the participant is interested in the sentence or not,especially when the text is easily comprehensible.At the individual level,eye movement behavior varies widely between individuals,and individuals manifest different characteristics in distinguishing reading interest and comprehensibility.

The emergence of SARS-CoV-2 variants of concern and repeated outbreaks of coronavirus epidemics in the past two decades emphasize the need for next-generation pan-coronaviral therapeutics. Drugging the multi-functional papain-like protease (PLpro) domain of the viral nsp3 holds promise. However, none of the known coronavirus PLpro inhibitors has been shown to be in vivo active. Herein, we screened a structurally diverse library of 50,080 compounds for potential coronavirus PLpro inhibitors and identified a noncovalent lead inhibitor F0213 that has broad-spectrum anti-coronaviral activity, including against the Sarbecoviruses (SARS-CoV-1 and SARS-CoV-2), Merbecovirus (MERS-CoV), as well as the Alphacoronavirus (hCoV-229E and hCoV-OC43). Importantly, F0213 confers protection in both SARS-CoV-2-infected hamsters and MERS-CoV-infected human DPP4-knockin mice. F0213 possesses a dual therapeutic functionality that suppresses coronavirus replication via blocking viral polyprotein cleavage, as well as promoting antiviral immunity by antagonizing the PLpro deubiquitinase activity. Despite the significant difference of substrate recognition, mode of inhibition studies suggest that F0213 is a competitive inhibitor against SARS2-PLpro via binding with the 157K amino acid residue, whereas an allosteric inhibitor of MERS-PLpro interacting with its 271E position. Our proof-of-concept findings demonstrated that PLpro is a valid target for the development of broad-spectrum anti-coronavirus agents. The orally administered F0213 may serve as a promising lead compound for combating the ongoing COVID-19 pandemic and future coronavirus outbreaks.
Animals ; Coronavirus Papain-Like Proteases/antagonists & inhibitors* ; Cricetinae ; Humans ; Mice ; Pandemics ; SARS-CoV-2/enzymology* ; COVID-19 Drug Treatment