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BACKGROUND: Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear. METHODS: We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects. We then validated and investigated the role of one of the identified proteins using in vitro cell cultures, in vivo animal models, and independent cohort of human samples. RESULTS: Plasma proteomics identified high protein abundance levels of B2M (β2-microglobulin) in patients with PH-HFpEF. Interestingly, both circulating and skeletal muscle levels of B2M were increased in mice with skeletal muscle SIRT3 (sirtuin-3) deficiency or high-fat diet-induced PH-HFpEF. Plasma and muscle biopsies from a validation cohort of PH-HFpEF patients were found to have increased B2M levels, which positively correlated with disease severity, especially pulmonary capillary wedge pressure and right atrial pressure at rest. Not only did the administration of exogenous B2M promote migration/proliferation in pulmonary arterial vascular endothelial cells but it also increased PCNA (proliferating cell nuclear antigen) expression and cell proliferation in pulmonary arterial vascular smooth muscle cells. Finally, B2m deletion improved glucose intolerance, reduced pulmonary vascular remodeling, lowered PH, and attenuated RV hypertrophy in mice with high-fat diet-induced PH-HFpEF. CONCLUSIONS: Patients with PH-HFpEF display higher circulating and skeletal muscle expression levels of B2M, the magnitude of which correlates with disease severity. Our findings also reveal a previously unknown pathogenic role of B2M in the regulation of pulmonary vascular proliferative remodeling and PH-HFpEF. These data suggest that circulating and skeletal muscle B2M can be promising targets for the management of PH-HFpEF.

Objective: Kleefstra Syndrome (KS) is a rare genetic disorder caused by a deletion at 9q34.3. Studies showed that various heart defects are observed in 41–43% of patients and abnormal features on brain imaging in 58–63%. To date, the prenatal phenotype in KS has yet to be defined. Case report: We present the first prenatal diagnosis and chromosomal microarray analysis (CMA) of a case of 9q34.3 microdeletion in a fetus with increased amniotic fluid, supported by abnormal prenatal ultrasound findings, and confirmed via autopsy. CMA revealed a 2.1 Mb 9q34.3 microdeletion encompassing an OMIM gene of EHMT1, which is consistent with the diagnosis of Kleefstra syndrome and 9q subtelomeric deletion syndrome. Conclusion: When a fetus with normal karyotype presents with polyhydramnios or abnormalities noted during second-trimester prenatal ultrasound screening, CMA analysis can be considered as the next step to rule out or confirm the diagnosis of chromosomal or other genetic aberrations.

AIM: To investigate the patterns of short-term intraocular pressure (IOP) fluctuations and identify the contributing factors following intravitreal injection in patients with retinal vascular diseases. METHODS: Totally 81 patients were enrolled in this case control study. Eyes were categorized into 7 groups, including age-related macular degeneration (AMD), polypoidal choroidal vasculopathy (PCV), idiopathic choroidal neovascularization (CNV), proliferative diabetic retinopathy (PDR), diabetic macular edema (DME), macular edema secondary to branch (BVOME) and central (CVOME) retinal vein occlusion. IOP was measured in all patients using rebound tonometer at 7 preset time points perioperatively. Additionally, based on the administered medication, the eyes were classified into three treatment groups, including dexamethasone intravitreal implant (IVO), intravitreal conbercept (IVC), and intravitreal ranibizumab (IVR). To compare IOP values at various time points across groups, we employed one-way ANOVA, independent sample t-test or χ2 test and multivariate logistic regression analysis. RESULTS: Peak IOP values across all groups were observed at 40s, and 5min after intravitreal injection. Statistical differences in IOP were detected at the 5min among the 7 indication groups (F=2.50, P=0.029). When examing the impact of medications, the IVO group exhibited lower average IOP values at both 40s and 5min compared to the IVC and IVR groups (P

Imposter syndrome can lead to feelings of self-doubt, fear of failure, overpreparation, procrastination, and guilt about subsequent success. Because imposter syndrome is linked to structural inequities, women of color (WOC) may be particularly impacted by feelings of imposter syndrome due to encounters with racism, sexism, and gender discrimination. Drawing from studies primarily focused on imposter syndrome among WOC, the authors offer recommendations for how school psychologists can learn from these scholars to inform their practice and counter feelings of imposter syndrome that may ensue in their own lives.

Three new species belonging to Basidiomycota from southwestern China are described based on morphological and molecular data. Campanophyllum microsporum is morphologically characterized by dorsally pseudostipitate, pale orange to brownish orange pileus, excentric to lateral pseudostipe, crowded lamellae, cylindrical-ellipsoid basidiospores 3.0–4.2 × 1.7–2.2 µm, narrowly clavate to clavate basidia 14.5–23.0 × 3.0–4.2 µm, and cylindrical to clavate cheilocystidia 22.0–55.0 × 5.0–10.8 µm. Calocera multiramosa is morphologically characterized by stipitate, yellowish to orange, dendroid, and dichotomously branched basidiomata, cylindrical to clavate basidia 36.5–52.5 × 3.8–6.1 µm, navicular or reniform, 1–5-septate mature basidiospores 10.4–16.7 × 5.2–7.4 µm. Dacrymyces naematelioides is morphologically characterized by stipitate and cerebriform, orange to light brown basidiomata, cylindrical to clavate, smooth or roughened basidia 38.5–79.5 × 6.5–10.6 µm, broadly and elliptic-fusiform, 7-septate mature basidiospores 18.5–28.6 × 8.9–13.8 µm. These three new species are supported by the phylogenetic analyses using maximum likelihood (ML) and Bayesian inference (BI) analyses with combined nuclear ribosomal DNA (rDNA) internal transcribed spacer (ITS) and large ribosomal subunit (LSU) sequences. Full descriptions and photographs of these new species are provided.

Carnosine dipeptidase 1 (CNDP1), an enzyme integral to the hydrolysis of dipeptides containing histidine, plays an indispensable role in myriad physiological processes, including hydrolysis of proteins, maturation of specific biochemical functionalities within proteins, tissue regeneration, and regulation of cell cycle. However, the implications of CNDP1 in oncogenesis and its prognostic value are not yet fully elucidated. Initially, we procured the GSE40367 dataset from the Gene Expression Omnibus and established a protein–protein interaction network. Thereafter, we conducted functional and pathway enrichment analyses utilizing GO, KEGG, and GSEA. Moreover, we undertook an association analysis concerning the expression of CNDP1 with immune infiltration, along with survival analysis across various cancers and specifically in hepatocellular carcinoma (HCC). Our study uncovered a total of 2,248 differentially expressed genes, with a down-regulation of CNDP1 in HCC and other cancers. Our explorations into the relationship between CNDP1 and immune infiltration disclosed a negative correlation between CNDP1 expression and the presence of immune cells in HCC. Survival analyses revealed that diminished expression of CNDP1 correlates with an adverse prognosis in HCC and several other types of cancer. These observations intimate that CNDP1 holds promise as a novel prognostic biomarker for both pan-cancer and HCC.

Purpose Studies have elucidated that heart failure (HF) in people living with HIV manifests differently when compared with HF cases in the general population. This cohort aimed to examine the mortality risk factors, including biological and social factors, as well as suitable medical interventions to prevent death in this population.Participants The New York City Health+Hospitals HIV Heart Failure (NYC4H) cohort encompassed records from 11 major hospital sites. Adult individuals with confirmed HIV and HF were recruited from either inpatient or clinic hospital visits between July 2017 and June 2022. The first follow-up period began on the date of the first clinical encounter until June 2023, and the second follow-up period extended between July 2022 and October 2023.Findings to date In total, 1044 patients were enrolled in the study. The cohort comprised 657 (62.9%) males and 387 (37.1%) females. The average age was 61.6 years at baseline and the average follow-up time was 3.8 years. Overall, a total of 259 (24.8%) deaths were identified, of which 193 occurred in the first follow-up period (enrolling date to June 2022) and 66 during the second follow-up period (June 2022 to October 2023). The most common comorbidities within this population were hypertension (75.3%), chronic obstructive pulmonary disease (39.2%), type II diabetes mellitus (40%) and hyperlipidaemia (35.7%). The most common social adversities were polysubstance use (31.13%), mental health-related issues (20.7%) and lack of family support (14.5%). 601 (57.6%) patients had encountered at least one and more than one social adversity in their lifetime.Future plans Currently, nutritional notes from licensed dietitians and right and left heart catheterisation reports are under review. We are scheduled to complete the data collection for the comprehensive third follow-up period, which includes follow-up psychosocial evaluations, by the end of 2025. In addition, we intend to conduct annual follow-ups for specific high-risk groups, such as individuals with pulmonary hypertension, those facing higher social adversities and participants with poor HIV control.

5G Multicast Broadcast Services (MBS) are viewed as a promising 5G New Radio (NR) application, as standardization begins in 3GPP Release 17. With MBS, one next generation Node B (gNB) delivers data to multiple user equipments (UE) simultaneously, thus improving spectrum efficiency. Millimeter wave (mmWave) beamforming further enhances system performance by focusing signals in a dedicated direction. However, despite the advantages, we identify three issues of multicast with beamforming techniques. First, link directionality causes the gNB to transmit data over the beams sequentially, resulting in a combinatorial resource allocation problem. Confronting this beam scheduling issue, we develop an optimization algorithm that obtains an optimal solution in polynomial time. Second, UEs may falsely report their valuations over beam resources to gain more utility. Under this scenario, the gNB cannot allocate the resources to those in need due to the lack of accurate UE information. Therefore, we propose a Vickrey-Clarke-Groves (VCG) auction-based mechanism to incentivize the UEs to reveal their valuations over resources truthfully. This mechanism guarantees solution efficiency and maximizes social welfare. Third, as 3GPP standards allow for different priorities for different multicast flows, and video content providers distinguish between ordinary and premium UEs, we take UE priority into account. In this regard, we extend the valuation-based mechanism to a multi-priority one. Finally, the mathematical analysis validates some desirable properties of the proposed scheme, such as incentive-compatibility. Simulation results also justify our superior performance in the 5G MBS system compared with other resource allocation schemes.

Abstract Isofagomine (IFG) and its analogues possess promising glycosidase inhibitory activities. However, a flexible synthetic strategy toward both C5a-functionalized IFGs remains to be explored. Here we show a practical synthesis of C5a-S and R aminomethyl IFG-based derivatives via the diastereoselective addition of cyanide to cyclic nitrone 1. Nitrone 1 was conveniently prepared on a gram scale and in high yield from inexpensive (−)-diethyl d-tartrate via a straightforward method, with a stereoselective Michael addition of a nitroolefin and a Nef reaction as key steps. A 268-membered library (134 × 2) of the C5a-functionalized derivatives was submitted to enzyme- or cell-based bio-evaluations, which resulted in the identification of a promising β-glucocerebrosidase (GCase) stabilizer demonstrating a 2.7-fold enhancement at 25 nM in p.Asn370Ser GCase activity and a 13-fold increase at 1 μM in recombinant human GCase activity in Gaucher cell lines.

Traditional village culture is an important part of rural culture as well as a precious heritage and historical memory of the Chinese nation, and its effective inheritance and sustainable development have attracted much attention. However, traditional village culture is often in a disadvantaged position in the process of urban-rural cultural exchanges, and the cultural adaptation problem of traditional village residents creates difficulties for the integration of urban-rural culture and the development of traditional cultural inheritance in China. In the context of traditional village conservation and tourism development, the cultural adaptation of traditional village residents is related to the resolution of the contradiction among traditional village development and conservation, the realization of the residents' good life, and the realization of the creative transformation and innovative development of traditional culture. Based on the literature on cultural adaptation, case summaries, and long-term field research experiences, this study clarifies the practical objectives of the cultural adaptation of tourism-driven traditional village residents, refines the process mechanism of their cultural adaptation by combining dimensions and processes, and explores the integration path of cultural adaptation based on positive psychology. The results show that first, the process mechanism of cultural adaptation of the residents of tourism-driven traditional villages can be investigated by combining the context of the evolution of urban-rural relationships in China and the U-curve theory of cultural adaptation. During the period of foreign culture entry, residents' external actions are actively cooperative, although their internal perceptions show foreign culture biases and development opportunity expectations. During the period of cultural clash and adjustment, conflicts and contradictions in daily life and behavioral expressions of residents are frequent, causing negative internal psychological emotions and cultural assimilation. The goal of the cultural integration period is that after a series of conflicts, residents will actively cooperate in their external behavior, and will be able to pass on their culture and seek progress. In terms of internal perceptions, residents will have increased psychological satisfaction, cultural confidence, and positive and open cultural perceptions. Further, borrowing from the research concept of positive psychology, we created a positive social organization system with three aspects: government macro-control, coordination of multiple groups, and a preventive supervision mechanism; a positive personality trait system with three aspects: cross-cultural interaction skills, ownership concept, and flexible and open cultural cognition; and a positive emotional experience system with three aspects: cultural identity, positive gaze of visitors, and community care. Based on the above systems, corresponding countermeasures to be taken at different stages of the cultural adaptation process are proposed to construct an integrated path of cultural adaptation for residents of traditional villages. This study explores the process mechanism and integration path of cultural adaptation of traditional village residents to deepen the interactive logic of locality and cultural adaptation, and provides a scientific reference for community governance and conservation practices in traditional villages, supporting traditional village locality protection and urban-rural integration.

Abstract Background The involvement of quality of life as the UNAIDS fourth 90 target to monitor the global HIV response highlighted the development of patient-reported outcome (PRO) measures to help address the holistic needs of people living with HIV/AIDS (PLWHA) beyond viral suppression. This study developed and tested preliminary measurement properties of a new patient-reported outcome (PROHIV-OLD) measure designed specifically to capture influences of HIV on patients aged 50 and older in China. Methods Ninety-three older people living with HIV/AIDS (PLWHA) were interviewed to solicit items and two rounds of patient cognitive interviews were conducted to modify the content and wording of the initial items. A validation study was then conducted to refine the initial instrument and evaluate measurement properties. Patients were recruited between February 2021 and November 2021, and followed six months later after the first investigation. Classical test theory (CTT) and item response theory (IRT) were used to select items using the baseline data. The follow-up data were used to evaluate the measurement properties of the final instrument. Results A total of 600 patients were recruited at the baseline. Of the 485 patients who completed the follow-up investigation, 483 were included in the validation sample. The final scale of PROHIV-OLD contained 25 items describing five dimensions (physical symptoms, mental status, illness perception, family relationship, and treatment). All the PROHIV-OLD dimensions had satisfactory reliability with Cronbach’s alpha coefficient, McDonald’s ω, and composite reliability of each dimension being all higher than 0.85. Most dimensions met the test-retest reliability standard except for the physical symptoms dimension (ICC = 0.64). Confirmatory factor analysis supported the structural validity of the final scale, and the model fit index satisfied the criterion. The correlations between dimensions of PROHIV-OLD and MOS-HIV met hypotheses in general. Significant differences on scores of the PROHIV-OLD were found between demographic and clinical subgroups, supporting known-groups validity. Conclusions The PROHIV-OLD was found to have good feasibility, reliability and validity for evaluating health outcome of Chinese older PLWHA. Other measurement properties such as responsiveness and interpretability will be further examined.

Summary: Background: Masked hypertension is associated with target organ damage (TOD) and adverse health outcomes, but whether antihypertensive treatment improves TOD in patients with masked hypertension is unproven. Methods: In this multicentre, randomised, double-blind, placebo-controlled trial at 15 Chinese hospitals, untreated outpatients aged 30–70 years with an office blood pressure (BP) of

Microvascular invasion (MVI) is an adverse prognostic indicator of tumor recurrence after surgery for hepatocellular carcinoma (HCC). Therefore, developing a nomogram for estimating the presence of MVI before liver resection is necessary. We retrospectively included 260 patients with pathologically confirmed HCC at the Fifth Medical Center of Chinese PLA General Hospital between January 2021 and April 2024. The patients were randomly divided into a training cohort (n = 182) for nomogram development, and a validation cohort (n = 78) to confirm the performance of the model (7:3 ratio). Significant clinical variables associated with MVI were then incorporated into the predictive nomogram using both univariate and multivariate logistic analyses. The predictive performance of the nomogram was assessed based on its discrimination, calibration, and clinical utility. Serum carnosine dipeptidase 1 ([CNDP1] OR 2.973; 95 % CI 1.167–7.575; p = 0.022), cirrhosis (OR 8.911; 95 % CI 1.922–41.318; p = 0.005), multiple tumors (OR 4.095; 95 % CI 1.374–12.205; p = 0.011), and tumor diameter ≥3 cm (OR 4.408; 95 % CI 1.780–10.919; p = 0.001) were independent predictors of MVI. Performance of the nomogram based on serum CNDP1, cirrhosis, number of tumors and tumor diameter was achieved with a concordance index of 0.833 (95 % CI 0.771–0.894) and 0.821 (95 % CI 0.720–0.922) in the training and validation cohorts, respectively. It fitted well in the calibration curves, and the decision curve analysis further confirmed its clinical usefulness. The nomogram, incorporating significant clinical variables and imaging features, successfully predicted the personalized risk of MVI in HCC preoperatively.

ABSTRACT The emerging prevalence of drug-resistant Staphylococcus aureus isolates underscores the urgent need for alternative therapeutic strategies due to the declining effectiveness of traditional antibiotics in clinical settings. MgrA, a key virulence regulator in S. aureus, orchestrates the expression of numerous virulence factors. Here, we report the discovery of isorhapontigenin, a methoxylated analog of resveratrol, as a potential anti-virulence agent against S. aureus. Isorhapontigenin effectively inhibits the hemolytic activity of S. aureus in a non-bactericidal manner. Additionally, it significantly reduces the cytotoxicity of S. aureus and impairs its ability to survive in macrophages. Mechanistically, isorhapontigenin modulates the expression of virulence factors, dose-dependently downregulating hla and upregulating the MgrA-regulated gene spa. Electrophoretic mobility shift assays demonstrated that isorhapontigenin inhibits the binding of MgrA to the hla promoter in a dose-dependent manner. Thermal shift assays confirmed the direct interaction between isorhapontigenin and the MgrA protein. The in vivo experiments demonstrated that isorhapontigenin significantly reduced the area of skin abscesses and improved survival in a pneumonia model while decreasing bacterial burden and inflammation in the lungs. In conclusion, isorhapontigenin holds potential as a candidate drug for further development as an anti-virulence agent for treating S. aureus infections.IMPORTANCEThe emergence of antibiotic-resistant Staphylococcus aureus strains presents a formidable challenge to public health, necessitating novel approaches in combating these pathogens. Traditional antibiotics are becoming increasingly ineffective, leading to a pressing need for innovative therapeutic strategies. In this study, targeting virulence factors that play a crucial role in the pathogenesis of bacterial infections offers a promising alternative to circumvent resistance mechanisms. The discovery of isorhapontigenin as an inhibitor of S. aureus virulence represents a significant advance in anti-virulence therapy.

ABSTRACT Polymyxin is used as a last resort antibiotics for infections caused by multi-drug resistant (MDR) Gram-negative bacteria and is often combined with other antibiotics to improve clinical effectiveness. However, the synergism of colistin and other antibiotics remains obscure. Here, we revealed a notable synergy between colistin and flavomycin, which was traditionally used as an animal growth promoter and has limited activity against Gram-negative bacteria, using checkerboard assay and time–kill curve analyses. The importance of membrane penetration induced by colistin was assessed by examining the intracellular accumulation of flavomycin and its antimicrobial impact on Escherichia coli (E. coli) strains with truncated lipopolysaccharides. Besides, a mutation in the flavomycin binding site was created to confirm its role in the observed synergy. This synergy is manifested as an augmented penetration of the E. coli outer membrane by colistin, leading to increased intracellular accumulation of flavomycin and enhanced cell killing thereafter. The observed synergy was dependent on the antimicrobial activity of flavomycin, as mutation of its binding site abolished the synergy. In vivo studies confirmed the efficacy of colistin combined with flavomycin against MDR E. coli infections. This study is the first to demonstrate the synergistic effect between colistin and flavomycin, shedding light on their respective roles in this synergism. Therefore, we propose flavomycin as an adjuvant to enhance the potency of colistin against MDR Gram-negative bacteria.IMPORTANCEColistin is a critical antibiotic in combating multi-drug resistant Gram-negative bacteria, but the emergence of mobilized colistin resistance (mcr) undermines its effectiveness. Previous studies have found that colistin can synergy with various drugs; however, its exact mechanisms with hydrophobic drugs are still unrevealed. Generally, the membrane destruction of colistin is thought to be the essential trigger for its interactions with its partner drugs. Here, we use clustered regularly interspaced palindromic repeats (CRISPR)–CRISPR-associated protein 9 (Cas9) for specifically mutating the binding site of one hydrophobic drug (flavomycin) and show that antimicrobial activity of flavomycin is critical for the synergy. Our results first give the evidence that the synergy is set off by colistin's membrane destruction and operated the final antimicrobial function by its partner drugs.

Abstract Background Social frailty (SF) is associated with multiple adverse health outcomes, yet there has been an inadequate focus on social frailty. The convoy model portrays the social networks through the perspective of the life course, thus providing a framework to explain the occurrence of social frailty. This study aimd to figure out the prevalence of social frailty and loneliness among community-dwelling older adults and to explore their correlations based on convoy model. Methods This was a cross-sectional study, and 295 older adults from 10 communities of Zhengzhou in Henan Province participated in the study. Social frailty and loneliness were assessed separately with the Social Frailty Scale and University of California at Los Angeles-Loneliness Scale. The scores of social frailty of the older adults in different characteristic communities were compared by independent sample t-test and single factor analysis of variance. The influencing factors of social frailty were analysed by multiple stepwise linear regression and the structural equation model. The correlation between social frailty and loneliness was analysed by Pearson correlation analysis. Results The total scores of social frailty and loneliness of the older adults in the community were (2.09 ± 1.53) and (43.19 ± 8.91), respectively. There was a moderate positive correlation between social frailty and loneliness (r = 0.621, P

Abstract Understanding temporal coherence in particulate matter (PM) pollution across East Asian outflow regions is crucial for collaborative efforts in addressing air pollution challenges. In this study, we analyze daily PM exceedance patterns using ground-based measurements over the past two decades, focusing on the influence of El Niño-Southern Oscillation (ENSO) and Asian dust activity. ENSO-related coherent PM exceedance shows lower occurrence during El Niño compared to La Niña in spring, due to weakened continental outflows and increased precipitation. Temporal distribution of dust-related coherent PM exceedance closely mirrors springtime dust activity in source regions, indicating significant dust emission impact on outflow regions. Our findings have implications for climate variability and the assessment of multi-decade model simulations.

Strains of the freshwater cyanobacterium Synechococcus elongatus were first isolated approximately 60 years ago, and PCC 7942 is well established as a model for photosynthesis, circadian biology, and biotechnology research. The recent isolation of UTEX 3055 and subsequent discoveries in biofilm and phototaxis phenotypes suggest that lab strains of S. elongatus are highly domesticated. We performed a comprehensive genome comparison among the available genomes of S. elongatus and sequenced two additional laboratory strains to trace the loss of native phenotypes from the standard lab strains and determine the genetic basis of useful phenotypes. The genome comparison analysis provides a pangenome description of S. elongatus, as well as correction of extensive errors in the published sequence for the type strain PCC 6301. The comparison of gene sets and single nucleotide polymorphisms (SNPs) among strains clarifies strain isolation histories and, together with large-scale genome differences, supports a hypothesis of laboratory domestication. Prophage genes in laboratory strains, but not UTEX 3055, affect pigmentation, while unique genes in UTEX 3055 are necessary for phototaxis. The genomic differences identified in this study include previously reported SNPs that are, in reality, sequencing errors, as well as SNPs and genome differences that have phenotypic consequences. One SNP in the circadian response regulator rpaA that has caused confusion is clarified here as belonging to an aberrant clone of PCC 7942, used for the published genome sequence, that has confounded the interpretation of circadian fitness research. IMPORTANCE Synechococcus elongatus is a versatile and robust model cyanobacterium for photosynthetic metabolism and circadian biology research, with utility as a biological production platform. We compared the genomes of closely related S. elongatus strains to create a pangenome annotation to aid gene discovery for novel phenotypes. The comparative genomic analysis revealed the need for a new sequence of the species type strain PCC 6301 and includes two new sequences for S. elongatus strains PCC 6311 and PCC 7943. The genomic comparison revealed a pattern of early laboratory domestication of strains, clarifies the relationship between the strains PCC 6301 and UTEX 2973, and showed that differences in large prophage regions, operons, and even single nucleotides have effects on phenotypes as wide-ranging as pigmentation, phototaxis, and circadian gene expression.