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Prevalence and determinants of anemia among HIV-positive children in central Uganda: A cross sectional study

PLoS ONE Abdirashid Dahir Herow, Ndeezi Grace, Joel Kimera et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0333825

Background Anemia remains a critical public health issue, especially in low-resource settings like Uganda, with severe consequences especially in HIV-positive children. Limited research has been conducted in low-income settings especially about anaemia in HIV-Positive children. This study aimed to determine the prevalence and factors associated with anemia among HIV positive children at Kayunga Regional Referral Hospital. In addition to assess iron deficiency anemia using Mentzer index. Methods This was a hospital based cross-sectional study conducted at KRRH. 384 HIV-positive children aged 6 months to 12 years attended the KRRH ART clinic between November 2024 to January 2025 were enrolled.Data was collected using structured questionnaires,information regarding their sociodemographic, medical and laboratory was obtained asking care giver or reviewing the medical record. Anthropometric measurements were done and interpreted compared to the WHO z-scores and obtained blood sample for CBC and analyzed. Anemia was defined based on age-specific hemoglobin thresholds: < 11.0 g/dL for children aged 6–59 months, < 11.5 g/dL for those aged 5–11 years, and <12.0 g/dL for children aged 12–14 years. Iron deficiency anemia was diagnosed with MI > 13. Logistic regression in STATA was done to determine the factors that were significantly associated with anaemia. Results Majority of the children (63.5%) were over 5 years of age and 52.9% were male and 57.3% had anemia with 95% confidence interval of 52.3–62.2%. The predominant severity category of anemia was moderate (48.6%). Multivariable analysis showed that caretakers who stopped in primary, having more than four siblings, being in current HIV stages 2 or 3, any history of hospital admission in the preceding six months, and being severely stunted, wasted, or experiencing concurrent stunting and wasting were independently associated with anemia among children infected with HIV (P-value < 0.05 for all). Iron deficiency anemia accounted for 54.1% of all children with anemia.

Automaticity speeds the retrieval of instances from the human hippocampus

Proceedings of the National Academy of Sciences Yuanyuan Zhang, Junxi Chen, Geoffrey F. Woodman et al. Nov 04, 2025 DOI: 10.1073/pnas.2518523122

Automatic processing allows humans to perform tasks with minimal effort following learning. Although theories of automaticity propose that learning should result in faster processing, studies have universally found that learning reduces the amplitude of neural activity, not that it speeds neural activity. Here, we show that with intracranial activity recorded from the hippocampus of twenty-two humans, we could decode the target the participant was about to report faster across learning. Theta oscillations in the hippocampus afforded faster decoding of the to-be-reported target as learning progressed, unlike in prefrontal and temporal regions of the cortex. Furthermore, hippocampal ripples (70 to 180 Hz bursts) appear to support memory retrieval after learning established automaticity. Our findings demonstrate that the hippocampus plays a key role in speeding memory retrieval of previous learning episodes as humans gain expertise, supporting a critical but untested prediction of learning theories.

Shading net and foliar applications of Si and K alleviates heat stress and improves pomegranate fruit quality

Scientific Reports Samira Moradi, Zabihollah Zamani, Reza Fatahi et al. Nov 04, 2025 DOI: 10.1038/s41598-025-22501-5

Evaluation of a new implant for Tibial Tuberosity Transposition in dogs: An ex vivo study

PLoS ONE Gabriel Rampanelli, Olicies da Cunha, Anderson Luiz de Carvalho et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0335274

The present study aims to describe and evaluate the effectiveness and potential applicability of a new implant designed to transpose the tibial tuberosity. The implant consists of a customized plate for fixation on the tibia, containing a hole for the insertion of a transposition screw in the tibial tuberosity. Computed tomography was performed on 21 cadaveric canine tibias to plan the surgical technique and calculate the desired transposition. Subsequently, an osteotomy of the tibial tuberosity was performed, extending 60% of the lateral cortex and 80% of the medial cortex to maintain a bone bridge between the tibial shaft and the osteotomized segment. After the osteotomy, the implant was fixed to the tibia, and the tibial tuberosity was transposed slowly and gradually using the transposition screw. The samples underwent radiographic evaluation and manual palpation following the application to detect tibial crest fractures. The plate’s shape adequately fit the medial surface of the tibia, and the implant was effective in promoting a slow and gradual transposition in canine cadavers without the need for an additional surgical device to perform the maneuver. The implant proved to be effective in achieving the desired transposition in a progressive, gradual, and slow manner.

Neutron crystallography of the covalent intermediate of β-glucosidase reveals remodeling of the catalytic center

Proceedings of the National Academy of Sciences Naomine Yano, Toma Kashima, Hiromu Arakawa et al. Nov 04, 2025 DOI: 10.1073/pnas.2502828122

Anomer-retaining glycoside hydrolases (GHs) generally catalyze a double displacement reaction via a covalent intermediate. However, neutron crystallography of glycoside ligand-bound states has not been performed. In this study, we investigated β-glucosidase Td2F2 from GH family 1 as a model enzyme for anomer-retaining GHs. We determined joint X-ray/neutron structures of Td2F2 in ligand-free form, covalent intermediate with a 2-deoxy-2-fluoro glucoside (2F-Glc) inhibitor, and glucose product complex using hydrogen/deuterium-exchanged crystals at room temperature, with neutron diffraction resolutions of 1.80–1.70 Å. Extensive hydrogen bonds recognizing the hydroxy groups of 2F-Glc were identified, along with the positions of deuterium atoms. The acid/base catalyst residue Glu166 was anchored by a hydrogen bond network pivoted by Asn293. Tyr295 forms a hydrogen bond with the catalytic nucleophile residue Glu352 in the ligand-free and glucose complex forms, while the active center undergoes significant reorganization, including side chain displacements of Glu352 and Tyr295, as well as the incorporation of a water molecule. An alternative conformation of Tyr295 was observed in the 2F-Glc structure at room temperature, suggesting its role in positioning the nucleophilic water during the deglycosylation step. Steady-state and pre-steady-state kinetic analyses of Y295F mutant supported the functional involvement of Tyr295 in both glycosylation and deglycosylation steps. The tyrosine hydrogen bonded to the nucleophile is also conserved in many other anomer-retaining GH families, underscoring its importance in catalysis. Based on the deuterium/hydrogen positions determined from neutron structures, we proposed a detailed reaction mechanism for Td2F2.

Generalized triangle group based S-box construction for secure image encryption

Scientific Reports Aqsa Zafar Abbasi, Ayesha Rafiq, Ines Hilali Jaghdam et al. Nov 04, 2025 DOI: 10.1038/s41598-025-22558-2

Green synthesis of silver nanoparticles from Brownlowia tersa leaf extract: multifaceted evaluation of antibacterial, antioxidant, cytotoxic, and anti-alzheimer potential

PLoS ONE Md Ridoy Hossain, Md Al Saber, Md. Anisul Hoque et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0335524

This study reports the first green synthesis of silver nanoparticles (AgNPs) using an aqueous leaf extract of Brownlowia tersa ( B. tersa ), confirming their formation via UV-Vis spectrophotometry with a peak at 472 nm. The AgNPs were evaluated for their antimicrobial and neuroprotective activities, particularly for Alzheimer’s disease. GC-MS and FT-IR analyses identified phenolics and flavonoids as the capping and reducing agents in the synthesis process. FESEM imaging showed nanoparticles of varied shapes and sizes, while EDX analysis confirmed the presence of silver, oxygen, and carbon. The antimicrobial activity was demonstrated with inhibition zones ranging from 8.5 to 10.5 mm against Staphylococcus aureus , Bacillus cereus , Shigella flexneri , and Pseudomonas aeruginosa at concentrations of 100 and 200 μg/disc, compared to control, deionised water. In antioxidant assays, AgNPs exhibited an IC₅₀ of 1533.448 μg/ml, significantly higher than L-ascorbic acid (IC₅₀: 83.948 μg/ml) and the plant extract (IC₅₀: 254.438 μg/ml), indicating weaker antioxidant properties of AgNPs. The cytotoxicity of the AgNPs was assessed using the brine shrimp lethality test, yielding LC₅₀ value of 13.50 μg/ml, indicating moderate toxicity. Neuropharmacological tests, except the elevated plus maze, on swiss albino mice revealed significant anxiolytic effects ( p < 0.05 ) and enhanced locomotor activity. Molecular docking studies of bioactive compounds from B. tersa leaves with Alzheimer’s and bacterial infection-related proteins revealed binding energies from −7.7 to −5.2 kcal/mol, with Benzamide, N-ethyl-N-[(4-ethylaminophenyl) sulfonyl]- and 3,4-Dihydroxyphenylglycol showing the strongest affinities. While the results are promising, the study acknowledges challenges in scaling up the synthesis process and emphasises the need for further research into the long-term biological effects and safety of AgNPs. Overall, B. tersa -derived AgNPs show great potential for therapeutic applications in bacterial infections and neurological disorders, but scalability and safety require more investigation.

Habenula–ventral tegmental area functional coupling and risk aversion in humans

Proceedings of the National Academy of Sciences Wanjun Lin, Jiahua Xu, Xiaoying Zhang et al. Nov 04, 2025 DOI: 10.1073/pnas.2500815122

Maladaptive responses to uncertainty, including excessive risk seeking or avoidance, are linked to a range of mental disorders. One expression of these is a provariance bias (PVB), i.e., risk-seeking manifests as a preference for choosing options with higher variances/uncertainty. Using a magnitude learning task, we show that individual differences in PVB are explained by a model that includes asymmetric learning rates, allowing differential learning from positive prediction errors (PPEs) and negative prediction errors (NPEs). Using high-resolution 7T functional MRI (fMRI), we identify distinct neural responses to PPEs and NPEs in value-sensitive regions, including habenula (Hb), ventral tegmental area (VTA), nucleus accumbens (NAcc), and ventral medial prefrontal cortex (vmPFC) in humans. Notably, prediction error signals in NAcc and vmPFC were boosted for high variance options. NPEs responses in NAcc were associated with a negative bias in learning rates that was linked to the strength of Hb-VTA negative functional coupling during NPE encoding, with a mediation analysis revealing this coupling influenced NAcc responses to NPEs via an impact on learning rate bias. Our findings implicate Hb-VTA functional coupling in the emergence of risk preferences during learning, with implications for psychopathology.

Specific recruitment properties of spinal reflex of thigh muscle in sprinter

Scientific Reports Gaku Kakehata, Kento Nakagawa, Naotsugu Kaneko et al. Nov 04, 2025 DOI: 10.1038/s41598-025-22504-2

Abstract Thigh muscles activation pattern plays a key role in high-performance sprint running. We investigated spinal neural mechanisms underlying sprinters’ specific thigh muscle control by examining spinal reflex recruitment properties and reciprocal inhibition of the thigh muscles in sprinters. Ten high-level national sprinters and ten controls participated in this study. Transcutaneous spinal cord stimulation (tSCS) was used to evoke spinal reflexes in biceps femoris (BF) and soleus (SOL) muscles. To assess the recruitment properties of thigh muscles, in Experiment 1, tSCS was applied at varying intensities to analyze recruitment curves. In Experiments 2–4, reciprocal inhibition of the thigh muscles was assessed under electrical stimulation, voluntary contraction, and muscle vibration. Sprinters exhibited a significantly steeper recruitment curve slope for BF spinal reflex compared to controls, whereas the groups did not differ for the SOL. Reciprocal inhibition from the rectus femoris to BF showed no significant differences between groups. These findings suggest that spinal neural circuits in sprinters undergo plastic changes, allowing higher motor output induced by reflexes with small changes in sensory input. This sprinter-specific spinal reflex recruitment, particularly in BF, likely aligns with their specific thigh muscle activation patterns.

Study on crude oil displacement efficiency by fracturing fluid in tight sandstone reservoir

PLoS ONE Jinfeng Li, Xingjun Gao, Lianru Yang et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0335233

Tight sandstone reservoirs usually experience a long flowback period after hydraulic fracturing, which significantly affects oil production. After fracturing, the well-soaking is commonly employed to control fracturing fluid flowback and enhance oil recovery, so that the oil in the reservoir matrix is replaced by fracturing fluid, which can improve the crude oil recovery and reduce the flowback of the fracturing fluid. In this paper, the gel breaking fluid of slick water fracturing fluid, guanidine gum fracturing fluid and cross-linked guanidine gum fracturing fluid are used as displacement working fluids to study the effect of gel breaking fluid on oil displacement in tight sandstone reservoirs. The results show that it is not the smaller the pore radius that the higher the displacement efficiency, but the oil displacement efficiency is higher for the equilibrium of capillary force and percolation resistance in a certain radius of pore throat. For tight sandstone reservoir, the oil displacement efficiency of small pore, middle pore and large pore is higher, the oil displacement efficiency of micro-pore is lower, and the oil in pore throat with radius less than 0.01 μm is difficult to be replaced. The lower the interfacial tension is, the lower the viscosity is, and the higher the oil displacement efficiency is. For tight sandstone reservoir, the displacement efficiency of crude oil can reach 13.11% −33.31%, the displacement of crude oil in the early stage is mainly displaced out of the middle and small pores, and then replaced out of the large pores and micro-pores of crude oil.

Programming cellular condensates for living materials using an intrinsically disordered protein display platform

Proceedings of the National Academy of Sciences Rong Chang, Hann X. Tu, Hongyu Ma et al. Nov 04, 2025 DOI: 10.1073/pnas.2510167122

Self-organization underpins the emergence of complex structure in living systems but remains a major challenge for engineering synthetic multicellular materials. Here, we present intrinsically disordered protein display platform (iDP 2 ), a generalizable platform for high-density display of intrinsically disordered proteins (IDPs) on the surface of Escherichia coli . iDP 2 uses CsgF as a surface-tethered scaffold, enabling efficient fusion and presentation of protein domains that lack stable tertiary structure. Successful display selectively favors disordered sequences, which, when endowed with phase separation propensity, drive the formation of dynamic cellular condensates. Programming cells with orthogonal IDPs enables sequence-specific segregation of mixed populations, allowing the design of spatially organized living assemblies. The aggregation state of these condensates is dynamically tunable by environmental cues such as ionic strength, and temperature, with responses predictable from the known phase behavior of the displayed IDPs. Extrusion processing of condensates generates macroscale filaments that maintain structural integrity and population segregation. By linking protein sequence to emergent collective behaviors, iDP 2 offers a programmable framework for rational control of cell–cell interactions. This approach establishes a foundation for engineering living materials with customizable viscoelastic properties, environmental responsiveness, and multicellular organization. More broadly, our work highlights the potential of disordered protein motifs as versatile tools for the design of adaptive, self-organizing biological systems.

Integrating RUSLE, AHP, GIS, and cloud-based geospatial analysis for soil erosion assessment under mediterranean conditions

Scientific Reports Mohamed E. Fadl, Mohammedi Zekari, Rima Labad et al. Nov 04, 2025 DOI: 10.1038/s41598-025-22503-3

Effects of COVID-19 pandemic lockdowns on college students’ physical fitness: A comparative study

PLoS ONE Jianzhong Sun, Minghao Wu, Jun Li et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0335309

Background The impact of the COVID-19 outbreak has been significant and far-reaching. This paper retrospectively examines its effects on changes in the physical fitness of university students. Method From 2018 to 2020, a comprehensive undergraduate institution in southern Anhui Province was selected to assess the impact of the COVID-19 pandemic on physical health indicators among college students. Results The overall physical fitness of students at Chizhou University was clustered near the passing threshold of 80.8%, with 13.0% of students failing to meet the standard. The COVID-19 pandemic contributed to an increased prevalence of overweight (11.3%) and obesity (4.4%) among the student population. In endurance running, both male and female students displayed a similar trend—initial improvement followed by a decline—resulting in reduced performance times by 16.7 s for males and 13.2 s for females in 2020. Notably, vital capacity and upper limb strength showed consistent upward trends from 2018 to 2020 for both genders. Specifically, male students’ vital capacity increased by 2.0% and 3.4%, and upper limb strength by 4.8% and 8.3%, in consecutive years. Similarly, female students’ vital capacity rose by 1.3% and 4.4%, while their upper limb strength improved by 3.9% and 3.5%, respectively. Conclusion The short-term impact of the COVID-19 epidemic significant effected college students’ endurance running performance. Future efforts should focus on the important long-term lagging effects of the pandemic. Meanwhile, there is an urgent need to better understand and develop alternative exercise modalities during major public health events to ensure the maintenance of physical fitness and overall health.

LRP8 is an entry receptor for tick-borne encephalitis viruses

Proceedings of the National Academy of Sciences Pengfei Li, Sean Hui, Zhenlu Chong et al. Nov 04, 2025 DOI: 10.1073/pnas.2525771122

Orthoflaviviruses are a genus of arthropod-transmitted RNA viruses that infect humans and other vertebrate animals on a global scale, resulting in extensive morbidity and mortality. Among the orthoflaviviruses, tick-borne encephalitis viruses (TBEV) are an antigenic group that causes severe neurological disease in humans. However, the entry receptors for TBEV, which contribute to cell and tissue tropism, remain largely unknown. Because recent studies identified members of the low-density lipoprotein receptor (LDLR) family as possible receptors for some orthoflaviviruses and distantly related alphaviruses, we performed a targeted screen in transgenic cells expressing different LDLR members and identified LRP8 (also called ApoER2) as a candidate receptor for TBEV strains from the five different subtypes. Genetic ablation of LRP8 impaired TBEV reporter virus particle or authentic virus infection in neuronal cells. Reciprocally, complementation or ectopic expression of LRP8 increased TBEV infection. LRP8 was used as a receptor by multiple strains of TBEV and several closely related tick-borne viruses but not by the mosquito-transmitted orthoflaviviruses we tested. LRP8 bound directly to TBEV envelope proteins and promoted virus attachment to and internalization in cells through LDLR type A (LA) binding domain, which we narrowed down to LA domains 1 and 2 through functional experiments. Soluble LRP8-Fc decoy receptors neutralized TBEV in cell culture, and reduced viral infection was observed in Lrp8 −/− neuronal cells obtained from knockout mice. Our studies establish a role for LRP8 in TBEV entry and infection, which has implications for the development of soluble receptor, antibody-based, and vaccine countermeasures.

Adaptive tuning of fractional order PID controllers for nonlinear processes using hybrid PSO DQN reinforcement learning

Scientific Reports Reza Shahouni, Masoud Bahraini, Moslem Abrofarakh et al. Nov 04, 2025 DOI: 10.1038/s41598-025-22509-x

Long-term potentiation and neurotransmitters expression and segregation are altered in the Metabolic Syndrome-associated dysautonomia

PLoS ONE Diana Elinos, Fernanda Veladiz-Gracia, Constanza González-Sierra et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0335728

The autonomic nervous system (ANS) dynamically regulates the internal environment to maintain homeostasis. The ANS exhibits some forms of synaptic plasticity, including long-term potentiation (LTP) and plastic changes in neurotransmitter distribution, both of which may contribute to autonomic function. Dysautonomia refers to an abnormality in the function of the ANS, with an imbalance between sympathetic and parasympathetic activity. Dysautonomia has been reported in conditions such as stress, hypertension, and metabolic syndrome (MS). MS is a cluster of risk factors for cardiovascular disease, diabetes, and premature death. In MS, the signs of dysautonomia include elevated plasma norepinephrine levels and increased arterial blood pressure. In this study, we characterized the effect of a high-sucrose diet (HSD) on synaptic plasticity in sympathetic ganglia of the rat by measuring LTP expression in the superior cervical ganglion (SCG) and analyzing the expression of acetylcholine (ACh) and GABA, as well as their balance of colocalization/segregation in ganglionic nerve terminals. The HSD consists of adding 30% sucrose to drinking water, which is an accepted model of MS. We observed an impairment in LTP expression, along with a decrease in ACh presence and a reduction in its segregation from GABA. These findings suggest the emergence of an inhibitory effect on synaptic transmission and plasticity within the SCG. We propose that dysautonomia associated with MS might involve changes in sympathetic activity, at least at the level of ganglionic cholinergic transmission. These results may help to improve our understanding of autonomic dysfunction in the context of this metabolic disorder.

A cell-based scrambling assay reveals the phospholipid headgroup preference of TMEM16F on the plasma membrane

Proceedings of the National Academy of Sciences Chin Fen Teo, Sami T. Tuomivaara, Niek van Hilten et al. Nov 04, 2025 DOI: 10.1073/pnas.2516822122

The asymmetric resting distribution of the three major phospholipid classes on the mammalian plasma membrane, with phosphatidylserine and phosphatidylethanolamine mostly on the inner leaflet and phosphatidylcholine mostly on the outer leaflet, is maintained by ATP-dependent flippases and floppases that exhibit headgroup selectivity. Upon signaling cues, this asymmetry can be dissipated by various phospholipid scramblases, allowing cells to respond to stimuli and adapt to different physiological contexts. The prevailing view in the field is that phospholipid scramblases on the plasma membrane act without headgroup preference. Here, we report contrary experimental evidence based on a phospholipid scrambling assay that quantifies the fluorescence polarization (FP) of nitrobenzoxadiazole (NBD)-labeled phospholipids for kinetic monitoring of phospholipid scrambling on the plasma membrane of living cells. Our experiments reveal that the plasma membrane-residing calcium-activated phospholipid scramblase TMEM16F preferentially acts on phosphatidylserine and phosphatidylcholine over phosphatidylethanolamine.

Network construction using sparse Gaussian graphical model based on GWAS summary statistics

Scientific Reports Megh Subedi, Xuewei Cao, Byung-Jun Kim et al. Nov 04, 2025 DOI: 10.1038/s41598-025-22475-4

Adolescent morphine exposure does not alter low-dose lipopolysaccharide (LPS)-induced sickness behavior in adult C57/BL6 mice

PLoS ONE Natalie V. Davidson, Cynthia Masese, Caitlin Han et al. Nov 04, 2025 DOI: 10.1371/journal.pone.0328026

Adolescent opioid use in the United States commands attention: millions of twelve- to nineteen-year-olds are exposed to opioids each year by prescription and misuse. Recent findings show that opioids bind not only to canonical opioid receptors but also interact with receptors on immune cells within both the central and peripheral nervous systems. The potential for early life opioid exposure to give rise to long-term changes in the neuroimmune system is not fully understood, particularly given the adolescent brain’s high susceptibility to neuroplastic changes. The goal of this study was to investigate the hypothesis that adolescent opioid use potentiates physiological and behavioral responses to lipopolysaccharide (LPS)-induced sickness later in life. To achieve this, we treated adolescent (postnatal day 35–42) male and female C57/BL6 mice with saline or bi-daily escalating doses of morphine for 5 days to model opioid dependence and, in adulthood (postnatal day 60–67), administered saline or a low dose of LPS (0.1 mg/kg) to promote an immune response. Body weight, body surface temperature, and locomotor activity were recorded up to 48 hours after LPS administration. Mice were also tested in the forced swim test 52 hours after LPS administration to assess depressive-like behavior. In contrast to our hypotheses, we found that adolescent morphine exposure had no additive effect on low-dose LPS-induced sickness measures when assessed in adulthood. These data suggest that adolescent opioid exposure may have minimal effects on future immune challenges, although further research is needed to confirm this.

Analgesia through FKBP51 inhibition at disease onset confers lasting relief from sensory and emotional chronic pain symptoms

Proceedings of the National Academy of Sciences Sara Hestehave, Roxana Florea, Samuel Singleton et al. Nov 04, 2025 DOI: 10.1073/pnas.2517405122

Chronic pain affects 20 to 30% of the population and imposes a significant socioeconomic burden as it is often accompanied by substantial emotional comorbidities such as anxiety and depression. Yet, the mechanisms underlying the interactions between the sensory and emotional aspects of chronic pain remain poorly understood. Here, we investigated the role of FKBP51, a regulator of the stress response, in mediating both sensory and emotional symptoms of chronic pain. Inhibition of FKBP51, via genetic deletion or pharmacological blockade, in persistent joint pain reduced fast-onset sensory, functional and activity-related symptoms, as well as late anxio-depressive comorbidities. FKBP51 inhibition after the establishment of the hypersensitive state provided only temporary symptoms relief, while acute inhibition at disease onset protected from the full development of sensory and anxio-depressive symptoms for up to 6 mo. Our results also indicated that early pain symptoms could predict the late sensory and emotional outcomes of chronic pain. RNA sequencing of spinal cord tissue revealed that late FKBP51 inhibition transiently altered nociceptive genes associated with mechanical hypersensitivity. In contrast, early inhibition persistently downregulated the Naaa gene, a key regulator of the transition to chronic pain, and reorganized spinal cilia. Our results indicate that early FKBP51 inhibition after injury can persistently reduce chronic pain and prevent the onset of associated emotional comorbidities by modulating critical spinal neurobiological pathways that play pivotal roles in the transition to chronic pain.