Cross-linking mass spectrometry (XL-MS) is widely used in the analysis of protein structure and protein-protein interactions (PPIs). Throughout the entire workflow, the utilization of cross-linkers and the interpretation of cross-linking data are the core steps. In recent years, the development of cross-linkers and analytical software mostly follow up on the classical models of non-cleavable cross-linkers such as BS3/DSS and MS-cleavable cross-linkers such as DSSO. Although such a paradigm promotes the maturity and robustness of the XL-MS field, it confines the innovation and flexibility of new cross-linkers and analytical software. This critical insight will discuss the classification, advantages, and disadvantages of existing data analysis search engines. Take the new platinum-based metal cross-linker as an example, potential pitfalls in characterization of cross-linked peptides using existing software are discussed. Finally, ideas on developing more flexible, comprehensive, and user-friendly cross-linkers and software tools are proposed.

Lower urinary tract symptoms (LUTS) are one of the most commonly described urination disorders worldwide. Previous investigations have focused predominantly on the prospective identification of cases that meet the researchers\' criteria; thus, the genuine demands regarding LUTS from patients and related issues may be neglected.
We aimed to examine web-based search trends and behaviors related to LUTS on a national and regional scale by using the dominant, major search engine in mainland China.
Baidu Index was queried by using LUTS-related terms for the period of January 2011 to September 2020. The search volume for each term was recorded to analyze search trends and demographic distributions. For user interest, user demand graph data and trend data were collected and analyzed.
Of the 13 LUTS domains, 11 domains are available in the Baidu Index database. The Baidu search index for each LUTS domain varied from 37.78% to 1.47%. The search trends for urinary frequency (2011-2018: annual percent change APC=7.82%; P<.001), incomplete emptying (2011-2014: APC=17.74%; P<.001), nocturia (2011-2018: APC=11.54%; P<.001), dysuria (2017-2020: APC=20.77%; P<.001), and incontinence (2011-2016: APC=13.39%; P<.001) exhibited fluctuations over time. The search index trends for weak stream (2011-2017: APC=-4.68%; P<.001; 2017-2020: APC=9.32%; P=.23), split stream (2011-2013: APC=9.50%; P=.44; 2013-2020: APC=2.05%; P=.71), urgency (2011-2018: APC=-2.63%; P=.03; 2018-2020: APC=8.58%; P=.19), and nocturnal enuresis (2011-2018: APC=-3.20%; P=.001; 2018-2020: APC=-4.21%; P=.04) remained relatively stable and consistent. The age distribution of the population for all LUTS-related inquiries showed that individuals aged 20 to 40 years made 73.86% (49,218,123/66,635,247) of the total search inquiries. Further, individuals aged 40 to 49 years made 12.29% (8,193,922/66,635,247) of the total search inquiries for all LUTS-related terms. People from the east part of China made 67.79% (45,172,031/66,635,247) of the total search queries. Additionally, most of the searches for LUTS-related terms were related to those for urinary diseases to varying degrees.
Web-based interest in LUTS-related terms fluctuated wildly and was reflected timely by Baidu Index in mainland China. The web-based search popularity of each LUTS-related term varied significantly and differed based on personal interests, the population\'s concerns, regional variations, and gender. These data can be used by care providers to track the prevalence of LUTS and the population\'s interests, guide the establishment of disease-specific health care policies, and optimize physician-patient health care sessions.

Search engines display helpline notices when people query for suicide-related information.
In this study, we aimed to examine if these notices and other information displayed in response to suicide-related queries are correlated with subsequent searches for suicide prevention rather than harmful information.
Anonymous suicide-related searches made on Bing and Google in the United States, the United Kingdom, Hong Kong, and Taiwan in a span of 10 months were extracted. Descriptive analyses and regression models were fit to the data to assess the correlation with observed behaviors.
Display of helpline notices was not associated with an observed change in the likelihood of or future suicide searches (P=.42). No statistically significant differences were observed in the likelihood of people making future suicide queries (both generally and specific types of suicide queries) when comparing search engines in locations that display helpline notices versus ones that do not. Pages with higher rank, being neutral to suicide, and those shown among more antisuicide pages were more likely to be clicked on. Having more antisuicide Web pages displayed was the only factor associated with further searches for suicide prevention information (hazard=1.18, P=.002).
Helpline notices are not associated with harm. If they cause positive change in search behavior, it is small. This is possibly because of the variability in intent of users seeking suicide-related information. Nonetheless, helpline notice should be displayed, but more efforts should be made to improve the visibility and ranking of suicide prevention Web pages.