Comparison of Negative Symptom Network Structures Between Patients With Early and Chronic Schizophrenia: A Network and Exploratory Graph Analysis.

BACKGROUND AND HYPOTHESIS: Despite the clinical relevance of negative symptoms in schizophrenia, our understanding of negative symptoms remains limited. Although various courses and stages of schizophrenia have been identified, variations in the negative symptom networks between distinct stages of schizophrenia remain unexplored. STUDY DESIGN: We examined 405 patients with early schizophrenia (ES) and 330 patients with chronic schizophrenia (CS) using the Scale for the Assessment of Negative Symptoms. Network analysis and exploratory graph analysis were used to identify and compare the network structures and community memberships of negative symptoms between the two groups. Further, associations between communities and social functioning were evaluated. The potential influences of other symptom domains and confounding factors were also examined. STUDY RESULTS: Multidimensional differences were found in the networks of negative symptoms between ES and CS. The global connectivity strength was higher in the network of ES than in the network of CS. In ES, central symptoms were mainly related to expressive deficits, whereas in CS they were distributed across negative symptom domains. A three-community structure was suggested across stages but with different memberships and associations with social functioning. Potential confounding factors and symptom domains, including mood, positive, disorganization, and excitement symptoms, did not affect the network structures. CONCLUSION: Our findings revealed the presence of stage-specific network structures of negative symptoms in schizophrenia, with negative symptom communities having differential significance for social functioning. These findings provide implications for the future development of tailored interventions to alleviate negative symptoms and improve functionality across stages.

Monopolar versus bipolar transurethral resection of bladder Tumour: post-hoc analysis of a prospective trial.

INTRODUCTION: Previously, in a randomised trial we demonstrated bipolar transurethral resection of bladder tumor (TURBT) could achieve a higher detrusor sampling rate than monopolar TURBT. We hereby report the long-term oncological outcomes following study intervention. METHODS: This is a post-hoc analysis of a randomized phase III trial comparing monopolar and bipolar TURBT. Only patients with pathology of non-muscle invasive bladder cancer (NMIBC) were included in the analysis. Per-patient analysis was performed. Primary outcome was recurrence-free survival (RFS). Secondary outcomes included progression-free survival (PFS), cancer-specific survival (CSS) and overall survival (OS). RESULTS: From the initial trial, 160 cases were randomised to receive monopolar or bipolar TURBT. 24 cases of non-urothelial carcinoma, 22 cases of muscle-invasive bladder cancer, and 9 cases of recurrences were excluded. A total of 97 patients were included in the analysis, with 46 in the monopolar and 51 in the bipolar group. The median follow-up was 97.1 months. Loss-to-follow-up rate was 7.2%. Regarding the primary outcome of RFS, there was no significant difference (HR = 0.731; 95%CI = 0.433-1.236; P = 0.242) between the two groups. PFS (HR = 1.014; 95%CI = 0.511-2.012; P = 0.969), CSS (HR = 0.718; 95%CI = 0.219-2.352; P = 0.584) and OS (HR = 1.135; 95%CI = 0.564-2.283; P = 0.722) were also similar between the two groups. Multifocal tumours were the only factor that was associated with worse RFS. CONCLUSION: Despite the superiority in detrusor sampling rate, bipolar TURBT was unable to confer long-term oncological benefits over monopolar TURBT.

Molecular insights into MpAGO1 and its regulatory miRNA, miR11707, in the high-temperature acclimation of Marchantia polymorpha.

As a model plant for bryophytes, Marchantia polymorpha offers insights into the role of RNA silencing in aiding early land plants navigate the challenges posed by high-temperature environments. Genomic analysis revealed unique ARGONAUTE1 ortholog gene (MpAGO1) in M. polymorpha that is regulated by two species-specific microRNAs (miRNAs), miR11707.1 and miR11707.2. Comparative studies of small RNA profiles from M. polymorpha cellular and MpAGO1 immunoprecipitation (MpAGO1-IP) profiles at various temperatures, along with analyses of Arabidopsis AGO1 (AtAGO1), revealed that MpAGO1 has a low-selectivity for a diverse range of small RNA species than AtAGO1. Protein structural comparisons revealed no discernible differences in the MID domains of MpAGO1 and AtAGO1, suggesting the complexity of miRNA species specificity and necessitating further exploration. Small RNA profiling and size exclusion chromatography have pinpointed a subset of M. polymorpha miRNAs, notably miR11707, that remain in free form within the cell at 22°C but are loaded into MpAGO1 at 28°C to engage in RNA silencing. Investigations into the mir11707 gene editing (mir11707ge) mutants provided evidence of the regulation of miR11707 in MpAGO1. Notably, while MpAGO1 mRNA expression decreases at 28°C, the stability of the MpAGO1 protein and its associated miRNAs is essential for enhancing the RISC activity, revealing the importance of RNA silencing in enabling M. polymorpha to survive thermal stress. This study advances our understanding of RNA silencing in bryophytes and provides groundbreaking insights into the evolutionary resilience of land plants to climatic adversities.

Bacteria extracellular vesicle as nanopharmaceuticals for versatile biomedical potential.

Bacteria extracellular vesicles (BEVs), characterized as the lipid bilayer membrane-surrounded nanoparticles filled with molecular cargo from parent cells, play fundamental roles in the bacteria growth and pathogenesis, as well as facilitating essential interaction between bacteria and host systems. Notably, benefiting from their unique biological functions, BEVs hold great promise as novel nanopharmaceuticals for diverse biomedical potential, attracting significant interest from both industry and academia. Typically, BEVs are evaluated as promising drug delivery platforms, on account of their intrinsic cell-targeting capability, ease of versatile cargo engineering, and capability to penetrate physiological barriers. Moreover, attributing to considerable intrinsic immunogenicity, BEVs are able to interact with the host immune system to boost immunotherapy as the novel nanovaccine against a wide range of diseases. Towards these significant directions, in this review, we elucidate the nature of BEVs and their role in activating host immune response for a better understanding of BEV-based nanopharmaceuticals' development. Additionally, we also systematically summarize recent advances in BEVs for achieving the target delivery of genetic material, therapeutic agents, and functional materials. Furthermore, vaccination strategies using BEVs are carefully covered, illustrating their flexible therapeutic potential in combating bacterial infections, viral infections, and cancer. Finally, the current hurdles and further outlook of these BEV-based nanopharmaceuticals will also be provided.

Androgen receptor-mediated pharmacogenomic expression quantitative trait loci: implications for breast cancer response to AR-targeting therapy.

BACKGROUND: Endocrine therapy is the most important treatment modality of breast cancer patients whose tumors express the estrogen receptor α (ERα). The androgen receptor (AR) is also expressed in the vast majority (80-90%) of ERα-positive tumors. AR-targeting drugs are not used in clinical practice, but have been evaluated in multiple trials and preclinical studies. METHODS: We performed a genome-wide study to identify hormone/drug-induced single nucleotide polymorphism (SNP) genotype - dependent gene-expression, known as PGx-eQTL, mediated by either an AR agonist (dihydrotestosterone) or a partial antagonist (enzalutamide), utilizing a previously well characterized lymphoblastic cell line panel. The association of the identified SNPs-gene pairs with breast cancer phenotypes were then examined using three genome-wide association (GWAS) studies that we have published and other studies from the GWAS catalog. RESULTS: We identified 13 DHT-mediated PGx-eQTL loci and 23 Enz-mediated PGx-eQTL loci that were associated with breast cancer outcomes post ER antagonist or aromatase inhibitors (AI) treatment, or with pharmacodynamic (PD) effects of AIs. An additional 30 loci were found to be associated with cancer risk and sex-hormone binding globulin levels. The top loci involved the genes IDH2 and TMEM9, the expression of which were suppressed by DHT in a PGx-eQTL SNP genotype-dependent manner. Both of these genes were overexpressed in breast cancer and were associated with a poorer prognosis. Therefore, suppression of these genes by AR agonists may benefit patients with minor allele genotypes for these SNPs. CONCLUSIONS: We identified AR-related PGx-eQTL SNP-gene pairs that were associated with risks, outcomes and PD effects of endocrine therapy that may provide potential biomarkers for individualized treatment of breast cancer.

Attentional Bias for Opioids in Taiwanese Heavy Smokers with Chronic Noncancer Pain.

Background and Objectives: Attentional bias (AB) for addictive substances is a feature of attention found in individuals with substance misuse or diagnosed with substance use disorders. When AB exists, the attention of the addicted individual may be quickly oriented to cues related to the addictive substance or be maintained on these cues for a longer time. AB toward opioids was found in Western samples of smokers with chronic noncancer pain. The level of AB was dose-responsive. However, similar studies in the Taiwanese population are lacking. This study compared the patterns of AB for opioid analgesics in Taiwanese participants with chronic noncancer pain to that of individuals without pain. This study aimed to investigate if AB toward opioids is presented in Taiwanese heavy smokers who are on long-term opioid therapy for pain control. Materials and Methods: Participants were grouped into chronic noncancer pain smokers, chronic pain nonsmokers, and smokers without pain, according to smoking habits and whether or not on long-term opioid therapy for pain control. Each participant completed demographic questionnaires, mood scales, and the opioid-related visual probe task. Differences in AB among the groups were compared using a three-way analysis of covariance controlling for daily cigarette consumption. Results: Chronic noncancer pain smokers (n = 17) and chronic pain nonsmokers (n = 16) displayed more severe levels of depression, anxiety, and pain, compared to smokers without pain (n = 28). Only did chronic pain nonsmokers show significant AB for opioid cues that were displayed for a short time. Analysis on reaction time found that smokers without pain consistently responded faster to the tasks. No difference in reaction time was found between the pain groups. Conclusions: The current study did not fully replicate findings from studies that were based in Western countries. Formulary availability and regulatory limitations might have affected patient's perception of prescription opioids in Taiwan. However, chronic pain nonsmokers exhibited initial orientation toward opioid-related cues when daily cigarette consumption was accounted for. According to previous research, this AB for shortly displayed opioid cues can be associated with the expectation of pain relief. The current finding also indicated general psychomotor retardation in individuals who were on long-term use of opioids.

Molecular autopsy in Chinese sudden cardiac death in the young.

Inherited cardiovascular conditions are significant causes of sudden cardiac death in the young (SCDY), making their investigation using molecular autopsy and prevention a public health priority. However, the molecular autopsy data in Chinese population is lacking. The 5-year result (2017-2021) of molecular autopsy services provided for victims of SCDY (age 1-40 years) was reviewed. The outcome of family cascade genetic screening and clinical evaluation was reviewed. A literature review of case series reporting results of molecular autopsy on SCDY in 2016-2023 was conducted. Among the 41 decedents, 11 were found to carry 13 sudden cardiac death (SCD)-causative genetic variants. Likely pathogenic (LP) variants were identified in the DSP, TPM1, TTN, and SCN5A genes. Cascade genetic testing identified four family members with LP variants. One family member with familial TPM1 variant was found to have hypertrophic cardiomyopathy upon clinical evaluation. This study provided insight into the genetic profile of molecular autopsy in a Chinese cohort of SCDY. The detection of important SCD-causative variants through molecular autopsy has facilitated family cascade screening by targeted genetic testing and clinical evaluation of at-risk family members. A literature review of the current landscape of molecular autopsy in the investigation of SCDY was conducted.

Mentalizing impairments and hypermentalizing bias in individuals with first-episode schizophrenia-spectrum disorder and at-risk mental state: the differential roles of neurocognition and social anxiety.

Mentalizing, or theory of mind (ToM), impairments and self-referential hypermentalizing bias are well-evident in schizophrenia. However, findings compared to individuals with at-risk mental states (ARMS) are inconsistent, and investigations into the relationship between social cognitive impairments and social anxiety in the two populations are scarce. This study aimed to examine and compare these deficits in first-episode schizophrenia-spectrum disorder (FES) and ARMS, and to explore potential specific associations with neurocognition and symptomatology. Forty patients with FES, 40 individuals with ARMS, and 40 healthy controls (HC) completed clinical assessments, a battery of neurocognitive tasks, and three social cognitive tasks. The comic strip and hinting tasks were used to measure non-verbal and verbal mentalizing abilities, and the gaze perception task was employed to assess self-referential hypermentalizing bias. FES and ARMS showed comparable mentalizing impairments and self-referential hypermentalizing bias compared to HC. However, only ambiguous self-referential gaze perception (SRGP) bias remained significantly different between three groups after controlling for covariates. Findings suggested that self-referential hypermentalizing bias could be a specific deficit and may be considered a potential behavioral indicator in early-stage and prodromal psychosis. Moreover, working memory and social anxiety were related to the social cognitive impairments in ARMS, whereas higher-order executive functions and positive symptoms were associated with the impairments in FES. The current study indicates the presence of stage-specific mechanisms of mentalizing impairments and self-referential hypermentalizing bias, providing insights into the importance of personalized interventions to improve specific neurocognitive domains, social cognition, and clinical outcomes for FES and ARMS.

Case report: Treatment response of NF-1-associated bladder ganglioneuroma to trametinib.

We present the clinical course of a 4-year-old girl with neurofibromatosis type 1-associated, unresectable, symptomatic urinary bladder ganglioneuroma. She was initially trialed on sirolimus without response and subsequently responded to MEK inhibitor trametinib, with improvement clinically and radiographically over 10 months. This report broadens the repertoire of therapeutic strategies for MEK inhibition in diseases related to the MAPK pathway.

Gestational age-specific reference intervals for androgens in pregnancy.

BACKGROUND: Androgen could impact cervical remodelling during pregnancy, and a higher level is associated with adverse pregnancy outcomes. A population-based gestation age-specific reference interval (RI) of total testosterone (TT), androstenedione (A4), and 17-hydroxyprogesterone (17-OHP) can help to diagnose maternal hyperandrogenism. METHODS: We enrolled 600 healthy Chinese women to obtain longitudinal serum samples across gestation. The serum androgen profile was measured by liquid chromatography-tandem mass spectrometry. The equations for medians of TT, A4, and 17-OHP were generated by MedCal, and the variances adjusted for 2-level modeling were generated by MLwiN, a system for the specification and analysis of a range of multilevel models. RESULTS: A4 and TT levels increased across the gestation, and they closely correlated with each other (R = 0.90, P=<0.001), whereas 17-OHP level decreased from 5th gestational week to 16th gestational week and then increased afterward towards the end of pregnancy. Women diagnosed with preeclampsia (PE) were found to have a significantly higher level of A4, TT, and 17-OHP when compared with non-PE cases with p ≤0.01, whereas mothers carrying male versus female fetuses have comparable levels of A4, TT, and 17-OHP. CONCLUSION: The study highlights a methodology for constructing gestational age-specific TT, A4, and 17-OHP levels to provide a better interpretation of results in a cohort of healthy Chinese women. The observation in PE supports previous findings, and the higher levels of TT, A4, and 17-OHP were observed before the onset of PE.

Evaluation of ImpENSA technology-enabled behaviour change module delivered to healthcare professionals in South Africa to improve micronutrient nutrition during the first 1000 days.

Healthcare professionals (HCPs) have vital roles in providing evidence-based care to promote healthy micronutrient nutrition in early life. Providing such care requires scalable training to strengthen knowledge and confident application of effective behaviour change skills. Among 33 public and private HCPs (primarily dietitians) in South Africa, we evaluated the behaviour change aspects of a technology-enabled National Qualification Sub-Framework level 6 programme, Improving Early Nutrition and Health in South Africa ('ImpENSA'). This programme comprises two self-directed micronutrient and behaviour change knowledge-based eLearning and one facilitated online practical skills modules to improve maternal and infant micronutrient nutrition. Using assessments, questionnaires and interviews, we collected data at baseline, after module completion and at 3-month follow-up after programme completion. Questionnaire and interview data showed major improvements in understanding of and attitudes towards person-centred behaviour change support immediately following the eLearning module on behaviour change. The assessment pass rate increased from 38% at baseline to 88% postmodule, demonstrating significant knowledge gain in behaviour change support. Intention to change practice towards a person-centred approach was high and many had already started implementing changes. Three months postprogramme, support was centred around patients' needs. Open relationships with patients, improved patient outcomes and increased job satisfaction were among reported outcomes. Many reported becoming better change facilitators and reflective practitioners. Additional improvements in understanding and attitudes to behaviour change support were evident, reinforced by making changes and experiencing positive outcomes. The findings suggest that technology-enabled learning can equip HCPs with knowledge and skills to effectively support behaviour change for healthy micronutrient nutrition during pregnancy and infancy.

Forecast Cosmological Constraints with the 1D Wavelet Scattering Transform and the Lyman-α Forest.

We make forecasts for the constraining power of the 1D wavelet scattering transform when used with a Lyman-α forest cosmology survey. Using mock simulations and a Fisher matrix, we show that there is considerable cosmological information in the scattering transform coefficients not captured by the flux power spectrum. We estimate mock covariance matrices assuming uncorrelated Gaussian pixel noise for each quasar at a level drawn from a simple log-normal model. The extra information comes from a smaller estimated covariance in the first-order wavelet power and from second-order wavelet coefficients that probe non-Gaussian information in the forest. Forecast constraints on cosmological parameters from the wavelet scattering transform are more than an order of magnitude tighter than for the power spectrum, shrinking a 4D parameter space by a factor of 10^{6}. Should these improvements be realized with the Dark Energy Spectroscopic Instrument, inflationary running would be constrained to test common inflationary models predicting α_{s}=-6×10^{-4} and neutrino mass constraints would be improved enough for a 5-σ detection of the minimal neutrino mass.

IL17RB genetic variants are associated with acamprosate treatment response in patients with alcohol use disorder: A proteomics-informed genomics study.

Acamprosate is a Food and Drug Administration (FDA) approved medication for the treatment of alcohol use disorder (AUD). However, only a subset of patients achieves optimal treatment outcomes. Currently, no biological measures are utilized to predict response to acamprosate treatment. We applied our established pharmaco-omics informed genomics strategy to identify potential biomarkers associated with acamprosate treatment response. Specifically, our previous open-label acamprosate clinical trial recruited 442 patients with AUD who were treated with acamprosate for three months. We first performed proteomics using baseline plasma samples to identify potential biomarkers associated with acamprosate treatment outcomes. Next, we applied our established "proteomics-informed genome-wide association study (GWAS)" research strategy, and identified 12 proteins, including interleukin-17 receptor B (IL17RB), associated with acamprosate treatment response.​ A GWAS for IL17RB concentrations identified several genome-wide significant signals. Specifically, the top hit single nucleotide polymorphism (SNP) rs6801605 with a minor allele frequency of 38% in the European American population mapped 4 kilobase (Kb) upstream of IL17RB, and intron 1 of the choline dehydrogenase (CHDH) gene on chromosome 3 (p: 4.8E-20). The variant genotype (AA) for the SNP rs6801605 was associated with lower IL17RB protein expression. In addition, we identified a series of genetic variants in IL17RB that were associated with acamprosate treatment outcomes. Furthermore, the variantgenotypes for all of those IL17RB SNPs were protective for alcohol relapse. Finally, we demonstrated that the basal level of mRNA expression of IL17RB was inversely correlated with those of nuclear factor-κB (NF-κB) subunits, and a significantly higher expression of NF-κB subunits was observed in AUD patients who relapsed to alcohol use. In summary, this study illustrates that IL17RB genetic variants might contribute to acamprosate treatment outcomes. This series of studies represents an important step toward generating functional hypotheses that could be tested to gain insight into mechanisms underlying acamprosate treatment response phenotypes. (The ClinicalTrials.gov Identifier: NCT00662571).

Clinical performance of ultrasonic backscatter parametric and nonparametric statistics in detecting early hepatic steatosis.

Diagnosis of early hepatic steatosis would allow timely intervention. B-mode ultrasound imaging was in question for detecting early steatosis, especially with a variety of concomitant parenchymal disease. This study aimed to use the surgical specimen as a reference standard to elucidate the clinical performance of ultrasonic echogenicity and backscatter parametric and nonparametric statistics in real-world scenarios. Ultrasound radio-frequency (RF) signals of right liver lobe and patient data were collected preoperatively. Surgical specimen was then used to histologically determine staging of steatosis. A backscatter nonparametric statistic (h), a known backscatter parametric statistic, i.e., the Nakagami parameter (m), and a quantitative echo intensity (env) were calculated. Among the 236 patients included in the study, 93 were grade 0 (<5% fat) and 143 were with steatosis. All the env, m and h statistics had shown significant discriminatory power of steatosis grades (AUC = 0.643-0.907 with p-value < 0.001). Mann-Whitney U tests, however, revealed that only the backscatter statistics m and h were significantly different between the groups of grades 0 and 1 steatosis. The two-way ANOVA showed a significant confounding effect of the elevated ALT on env (p-value = 0.028), but no effect on m or h. Additionally, the severe fibrosis was found to be a significant covariate for m and h. Ultrasonic signals acquired from different scanners were found linearly comparable.

Safety and Efficacy of Immediate Hyperthermic Intravesical Chemotherapy Following Transurethral Resection of Bladder Tumour (I-HIVEC).

The recurrence rate following endoscopic treatment of non-muscle-invasive bladder cancer (NMIBC) remains high. Standard treatment includes intravesical instillation of chemotoxic agents such as mitomycin C (MMC) to reduce recurrence. It is postulated that upfront administration of hyperthermic intravesical MMC (HIVEC) immediately after transurethral resection of bladder tumour (TURBT) may enhance its efficacy, but evidence from human trials is scant. This pilot study explored the safety of immediate intravesical MMC instillation following TURBT using a conductive HIVEC system (Combat BRS). Patients diagnosed with papillary bladder tumours scheduled for TURBT were recruited. Among 29 patients treated with HIVEC, there was minimal additional postoperative morbidity. The majority (79.3%) were discharged after a hospital stay of 1 d, and no patient required bladder irrigation. There were six grade I-II adverse events (20.7%) and one grade III event (3.4%). No recurrences were observed within 3 mo, and the 12-mo recurrence rate was 4.5%. The study findings demonstrate that immediate HIVEC MMC instillation following TURBT is safe. Further research is needed to assess long-term efficacy in comparison to standard cold MMC. PATIENT SUMMARY: Non-muscle-invasive bladder cancer is treated with tumour removal via a telescope inserted into the bladder through the urethra (called TURBT). We tested the safety of treating the bladder with a warm solution of a chemotherapy drug (mitomycin C) immediately after TURBT, as this may prevent tumour recurrence. The treatment was safe and well tolerated. Further trials are needed with more patients and longer follow-up to confirm the results.

Long-Term Outcomes of Orthotopic Neobladder Versus Ileal Conduit Urinary Diversion in Robot-Assisted Radical Cystectomy (RARC): Multicenter Results from the Asian RARC Consortium.

PURPOSE: Robot-assisted radical cystectomy (RARC) has gained traction in the management of muscle invasive bladder cancer. Urinary diversion for RARC was achieved with orthotopic neobladder and ileal conduit. Evidence on the optimal method of urinary diversion was limited. Long-term outcomes were not reported before. This study was designed to compare the perioperative and oncological outcomes of ileal conduit versus orthotopic neobladder cases of nonmetastatic bladder cancer treated with RARC. PATIENTS AND METHODS: The Asian RARC consortium was a multicenter registry involving nine Asian centers. Consecutive patients receiving RARC were included. Cases were divided into the ileal conduit and neobladder groups. Background characteristics, operative details, perioperative outcomes, recurrence information, and survival outcomes were reviewed and compared. Primary outcomes include disease-free and overall survival. Secondary outcomes were perioperative results. Multivariate regression analyses were performed. RESULTS: From 2007 to 2020, 521 patients who underwent radical cystectomy were analyzed. Overall, 314 (60.3%) had ileal conduit and 207 (39.7%) had neobladder. The use of neobladder was found to be protective in terms of disease-free survival [Hazard ratio (HR) = 0.870, p = 0.037] and overall survival (HR = 0.670, p = 0.044) compared with ileal conduit. The difference became statistically nonsignificant after being adjusted in multivariate cox-regression analysis. Moreover, neobladder reconstruction was not associated with increased blood loss, nor additional risk of major complications. CONCLUSIONS: Orthotopic neobladder urinary diversion is not inferior to ileal conduit in terms of perioperative safety profile and long-term oncological outcomes. Further prospective studies are warranted for further investigation.

Precisely Controlling Polymer Acceptors with Weak Intramolecular Charge Transfer Effect and Superior Coplanarity for Efficient Indoor All-Polymer Solar Cells with over 27% Efficiency.

Indoor photovoltaics (IPVs) are garnering increasing attention from both the academic and industrial communities due to the pressing demand of the ecosystem of Internet-of-Things. All-polymer solar cells (all-PSCs), emerging as a sub-type of organic photovoltaics, with the merits of great film-forming properties, remarkable morphological and light stability, hold great promise to simultaneously achieve high efficiency and long-term operation in IPV's application. However, the dearth of polymer acceptors with medium-bandgap has impeded the rapid development of indoor all-PSCs. Herein, a highly efficient medium-bandgap polymer acceptor (PYFO-V) is reported through the synergistic effects of side chain engineering and linkage modulation and applied for indoor all-PSCs operation. As a result, the PM6:PYFO-V-based indoor all-PSC yields the highest efficiency of 27.1% under LED light condition, marking the highest value for reported binary indoor all-PSCs to date. More importantly, the blade-coated devices using non-halogenated solvent (o-xylene) maintain an efficiency of over 23%, demonstrating the potential for industry-scale fabrication. This work not only highlights the importance of fine-tuning intramolecular charge transfer effect and intrachain coplanarity in developing high-performance medium-bandgap polymer acceptors but also provides a highly efficient strategy for indoor all-PSC application.