Simultaneous SERS Sensing of Cysteine and Homocysteine in Blood Based on the CBT-Cys Click Reaction: Toward Precisive Diagnosis of Schizophrenia.

At present, there is a lack of sufficiently specific laboratory diagnostic indicators for schizophrenia. Serum homocysteine (Hcy) levels have been found to be related to schizophrenia. Cysteine (Cys) is a demethylation product in the metabolism of Hcy, and they always coexist with highly similar structures in vivo. There are few reports on the use of Cys as a diagnostic biomarker for schizophrenia in collaboration with Hcy, mainly because the rapid, economical, accurate, and high-throughput simultaneous detection of Cys and Hcy in serum is highly challenging. Herein, a click reaction-based surface-enhanced Raman spectroscopy (SERS) sensor was developed for simultaneous and selective detection of Cys and Hcy. Through the efficient and specific CBT-Cys click reaction between the probe containing cyan benzothiazole and Cys/Hcy, the tiny methylene difference between the molecular structures of Cys and Hcy was converted into the difference between the ring skeletons of the corresponding products that could be identified by plasmonic silver nanoparticle enhanced molecular fingerprint spectroscopy to realize discriminative detection. Furthermore, the SERS sensor was successfully applied to the detection in related patient serum samples, and it was found that the combined analysis of Cys and Hcy can improve the diagnostic accuracy of schizophrenia compared to a single indicator.

Human Airway Organoids and Multimodal Imaging-Based Toxicity Evaluation of 1-Nitropyrene.

Despite significant advances in understanding the general health impacts of air pollution, the toxic effects of air pollution on cells in the human respiratory tract are still elusive. A robust, biologically relevant in vitro model for recapitulating the physiological response of the human airway is needed to obtain a thorough understanding of the molecular mechanisms of air pollutants. In this study, by using 1-nitropyrene (1-NP) as a proof-of-concept, we demonstrate the effectiveness and reliability of evaluating environmental pollutants in physiologically active human airway organoids. Multimodal imaging tools, including live cell imaging, fluorescence microscopy, and MALDI-mass spectrometry imaging (MSI), were implemented to evaluate the cytotoxicity of 1-NP for airway organoids. In addition, lipidomic alterations upon 1-NP treatment were quantitatively analyzed by nontargeted lipidomics. 1-NP exposure was found to be associated with the overproduction of reactive oxygen species (ROS), and dysregulation of lipid pathways, including the SM-Cer conversion, as well as cardiolipin in our organoids. Compared with that of cell lines, a higher tolerance of 1-NP toxicity was observed in the human airway organoids, which might reflect a more physiologically relevant response in the native airway epithelium. Collectively, we have established a novel system for evaluating and investigating molecular mechanisms of environmental pollutants in the human airways via the combinatory use of human airway organoids, multimodal imaging analysis, and MS-based analyses.

Exposure to real-ambient bedroom light at night delayed circadian rhythm in healthy Chinese young adults: A cross-sectional study.

BACKGROUND: Light at night (LAN) have attracted increased research attention on account of its widespread health hazards. However, the underlying mechanism remains unknown. The objective of this study was to investigate the effects of real-ambient bedroom LAN exposure on circadian rhythm among young adults and potential sex differences. METHODS: Bedroom LAN exposure was measured at 60-s intervals for 2 consecutive days using a portable illuminance meter. Circadian phase was determined by the dim light melatonin onset (DLMO) time in 7 time-series saliva samples. RESULTS: The mean age of the 142 participants was 20.7 ± 0.8 years, and 59.9% were women. The average DLMO time was 21:00 ± 1:11 h, with men (21:19 ± 1:12 h) later than women (20:48 ± 1:07 h). Higher level of LAN intensity (LANavg ≥ 3lx vs. LANavg < 3lx) was associated with an 81.0-min later in DLMO time (95% CI: 0.99, 1.72), and longer duration of nighttime light intensity ≥ 5lx (LAN5; LAN5 ≥ 45 min vs. LAN5 < 45 min) was associated with a 51.6-min later in DLMO time (95% CI: 0.46, 1.26). In addition, the delayed effect of LAN exposure on circadian phase was more pronounced in men than in women (all P-values <0.05). CONCLUSIONS: Overall, bedroom LAN exposure was significantly associated with delayed circadian rhythm. Additionally, the delayed effect is more significant in men. Keeping bedroom dark at night may be a practicable option to prevent circadian disruption and associated health implications. Future studies with more advanced light measurement instrument and consensus methodology for DLMO assessment are warranted.

Real-ambient bedroom light at night increases systemic inflammation and disrupts circadian rhythm of inflammatory markers.

BACKGROUND: Exposure to light at night (LAN) has been associated with multiple adverse health outcomes. However, evidence is limited regarding the impacts of LAN exposure on human inflammation. OBJECTIVES: To examine the association between real-ambient bedroom LAN exposure with systemic inflammation and circadian rhythm of inflammatory markers. METHODS: Using data from a prospective cohort study of Chinese young adults. At baseline, bedroom LAN exposure was measured with a portable illuminance meter; fasting blood sample for high-sensitivity C-reactive protein (hs-CRP) assay was collected. At 3-year follow-up, 20 healthy young adults (10 LANavg < 5 lx, 10 LANavg ≥ 5 lx) were recruited from the same cohort; time-series venous blood samples were sampled every 4 h over a 24 h-cycle for the detection of 8 inflammatory markers. Circadian rhythm of inflammatory markers was assessed using cosinor analysis. RESULTS: At baseline, the average age of the 276 participants was 18.7 years, and 33.3 % were male. Higher levels of bedroom LAN exposure were significantly associated with increased hs-CRP levels. The association between bedroom LAN exposure and systemic inflammation was only significant in the inactive group (MVPA < 2 h/d) but not in the physically active group (MVPA ≥ 2 h/d). In addition, exposure to higher levels of nighttime light (LANavg ≥ 5 lx) disrupted circadian rhythms (including rhythmic expression, circadian amplitude and circadian phase) of some inflammatory cytokines and inflammatory balance indicators. CONCLUSION: Exposure to bedroom nighttime light increases systemic inflammation and disrupts circadian rhythm of inflammatory markers. Keep bedroom darkness at night may represent important strategies for the prevention of chronic inflammation. Additionally, for people living a community with higher nighttime light pollution, regular physical activity may be a viable option to counteract the negative impacts of LAN exposure on chronic inflammation.

In Situ Transmission Electron Microscopy Investigation on Oriented Attachment of Nanodiamonds.

Oriented attachment (OA) plays an important role in the assembly of nanoparticles and the regulation of their size and morphology, which is expected to be an effective means to modulate the properties of nanodiamonds (NDs). However, there remains a dearth of comprehensive investigation into the OA mechanism of NDs. Using in situ transmission electron microscopy, we conducted atomic-resolution investigation on the OA events of ND pairs under electron beam irradiation. The occurrence of an OA event is contingent upon the alignment between two ND surfaces, and the coalesced particles undergo recrystallization to form spherical shapes. Both experimental observations and molecular dynamics (MD) simulations reveal that ND pairs exhibit a preference for coalescing along the {111} surfaces. Additionally, MD simulations indicate that kinetic factors, such as contact surface area and contact angle, also influence the coalescence process.

Shifting levels of peripheral inflammatory profiles as an indicator for comorbid multiple autoimmune diseases and bipolar disorder: a case report.

Autoimmune diseases (AID) cause inflammatory changes in the peripheral blood, which might be a predisposing factor for the development of comorbid bipolar disorder (BD). The levels of peripheral inflammatory indicators and cytokines may also serve as potential biomarkers for predicting BD susceptibility and the efficacy of antipsychotics in patients with AID. Herein, we present the case of a 43-year-old female who has suffered from AID for over 16 years and was recently diagnosed with "bipolar and related disorder due to another medical condition".

Tubal ectopic pregnancy: a retrospective cohort study on clinical characteristics, treatment options and reproductive outcomes within 5 years.

PURPOSE: To investigate the association between different treatments of tubal ectopic pregnancy (EP) -expectant management, methotrexate (MTX), selected or recommended laparoscopic surgery-and the subsequent reproductive outcomes. METHODS: We conducted a retrospective cohort study including 228 EPs. The patients were divided into four treatment groups: 28 (12.3%) with expectant management successfully, 60 (26.3%) with MTX successfully, 140 patients with laparoscopic salpingectomy, of which 47 (20.6%) were assigned to selected surgery group because they opted for surgical treatment versus MTX, 93 (40.8%) were assigned to recommended surgery group as recommended by the attending physician. RESULTS: The recommended surgery group had the lowest rate of intrauterine pregnancy (IUP) (77.42%) and live birth (LB) (72.04%), while the incidence of recurrent EP (REP) (20.43%) was the highest, but the statistical differences were not significant. We did not observe significant differences of the EP-IUP time interval, rates of LB and miscarriage (MIS) between the four groups. Compared to the MTX group, recommended surgery was negatively associated with IUP (adjusted OR, 95%CI: 0.34, 0.11-1.03) and LB (0.35, 0.14-0.92), while it had higher risk for REP (3.48, 1.03-11.74) in the subsequent pregnancy. Further, compared to selective surgery group, recommended surgery was negatively associated with IUP (0.15, 0.03-0.68) and LB (0.23, 0.07-0.74), while it had higher risk for REP (6.83, 1.43-32.67) in the subsequent pregnancy. Expectant treatment was negatively associated with assisted reproductive technology (ART) (0.08, 0.02-0.40) compared with MTX. Of the185 patients who had LBs, all adverse outcomes were not statistically different between the four groups. CONCLUSION: Patients with recommended laparoscopic salpingectomy had worse reproductive outcomes than the other treatment groups. The disease status of EP may play an important role in the association rather than the surgery alone.

Cross-Modal Object Detection Based on a Knowledge Update.

As an important field of computer vision, object detection has been studied extensively in recent years. However, existing object detection methods merely utilize the visual information of the image and fail to mine the high-level semantic information of the object, which leads to great limitations. To take full advantage of multi-source information, a knowledge update-based multimodal object recognition model is proposed in this paper. Specifically, our method initially uses Faster R-CNN to regionalize the image, then applies a transformer-based multimodal encoder to encode visual region features (region-based image features) and textual features (semantic relationships between words) corresponding to pictures. After that, a graph convolutional network (GCN) inference module is introduced to establish a relational network in which the points denote visual and textual region features, and the edges represent their relationships. In addition, based on an external knowledge base, our method further enhances the region-based relationship expression capability through a knowledge update module. In summary, the proposed algorithm not only learns the accurate relationship between objects in different regions of the image, but also benefits from the knowledge update through an external relational database. Experimental results verify the effectiveness of the proposed knowledge update module and the independent reasoning ability of our model.

A new simple method for quantification of cilostazol and its active metabolite in human plasma by LC-MS/MS: Application to pharmacokinetics of cilostazol associated with CYP genotypes in healthy Chinese population.

A simple, sensitive, and fully automated liquid chromatography-tandem mass spectrometry (LC-MS/MS) method was developed and validated for the simultaneous quantification of cilostazol (CIL) and its active metabolite, 3,4-dehydro cilostazol (CIL-M), in human plasma. Plasma samples were processed by protein precipitation in 2 mL 96-deep-well plates, and all liquid transfer steps were performed through robotic liquid handling workstation, enabling the whole procedure fast, compared to the reported methods. Separation of analytes was successfully achieved on a UPLC BEH C18 column (2.1 × 100 mm, 1.7 µm) with mobile phase A (5 mM ammonium formate containing 0.1% formic acid) and mobile phase B (methanol) at a flow rate of 0.30 mL min-1 . The total run time was 3.5 min per sample. Mass spectrometric detection was conducted by electrospray ion source in positive ion multiple reaction monitoring mode. Calibration curves were linear over the concentration range of 1.0-800 ng·mL-1 for CIL and 0.05-400 ng·mL-1 for CIL-M. The coefficient of variation for the assay's precision was 12.3%, and the accuracy was 88.8-99.8%. It was fully validated and successfully applied to assess the influence of CYP genotypes on the pharmacokinetics of CIL after oral administration of 50 mg tablet formulations of CIL to healthy Chinese volunteers. The results suggest that, in Chinese population, the genotype of CYP3A5 affects the plasma exposure of CIL.

Anomalous Shape Evolution of Ag2O2 Nanocrystals Modulated by Surface Adsorbates during Electron Beam Etching.

An understanding of nanocrystal shape evolution is significant for the design, synthesis, and applications of nanocrystals with surface-enhanced properties such as catalysis or plasmonics. Surface adsorbates that are selectively attached to certain facets may strongly affect the atomic pathways of nanocrystal shape development. However, it is a great challenge to directly observe such dynamic processes in situ with a high spatial resolution. Here, we report the anomalous shape evolution of Ag2O2 nanocrystals modulated by the surface adsorbates of Ag clusters during electron beam etching, which is revealed through in situ transmission electron microscopy (TEM). In contrast to the Ag2O2 nanocrystals without adsorbates, which display the near-equilibrium shape throughout the etching process, Ag2O2 nanocrystals with Ag surface adsorbates show distinct facet development during etching by electron beam irradiation. Three stages of shape changes are observed: a sphere-to-a cube transformation, side etching of a cuboid, and bottom etching underneath the surface adsorbates. We find that the Ag adsorbates modify the Ag2O2 nanocrystal surface configuration by selectively capping the junction between two neighboring facets. They prevent the edge atoms from being etched away and block the diffusion path of surface atoms. Our findings provide critical insights into the modulatory function of surface adsorbates on the shape control of nanocrystals.

SNCA rs11931074 polymorphism correlates with spontaneous brain activity and motor symptoms in Chinese patients with Parkinson's disease.

The α-synuclein (SNCA) gene is thought to be involved in levels of α-synuclein and influence the susceptibility for the development of Parkinson's disease (PD). The aim of the present study is to explore the association among SNCA rs1193074 polymorphism, spontaneous brain activity and clinical symptoms in PD patients. 62 PD patients and 47 healthy controls (HC) were recruited and underwent resting-state functional magnetic resonance imaging (rs-fMRI) scans. Also blood sample of each participant was genotyped for rs11931074 polymorphism (PD: TT = 19, GT = 32, GG = 11; HC: TT = 10, GT = 25, GG = 12) and then examined to ascertain the influence of different genotypes on regional brain activity with amplitude low-frequency fluctuation analysis (ALFF). Furthermore, we evaluated the relationship among genotypes, interactive brain region and clinical symptoms in PD. Compared with HC subjects, PD patients showed decreased ALFF values in right lingual gyrus and increased ALFF values in right cerebellum posterior lobe. Significant interaction of ''groups × genotypes'' was found in the right angular gyrus, where there were higher ALFF values in TT genotype than in GT or GG genotype in the PD group and there was a contrary trend in the HC group. And further Spearman's correlative analyses revealed that ALFF values in right angular gyrus were negatively associated with unified Parkinson's disease rating scale (UPDRS) III score in PD-TT genotype. Our study shows for the first time that SNCA rs11931074 polymorphism might modulate brain functional alterations and correlate with motor symptoms in Chinese PD patients.

Correlations between abnormal iron metabolism and non-motor symptoms in Parkinson's disease.

Despite a growing body of evidence suggests that abnormal iron metabolism plays an important role in the pathogenesis of Parkinson's disease (PD), few studies explored its role in non-motor symptoms (NMS) of PD. The present study aimed to investigate the relationship between abnormal iron metabolism and NMS of PD. Seventy PD patients and 64 healthy controls were consecutively recruited to compare serum iron, ceruloplasmin, ferritin, and transferrin levels. We evaluated five classic NMS, including depression, anxiety, pain, sleep disorder, and autonomic dysfunction in PD patients using the Hamilton Depression Scale (HAMD), the Hamilton Anxiety Scale (HAMA), the short form of the McGill Pain Questionnaire, the Pittsburgh Sleep Quality Index and the Scale for Outcomes in Parkinson's disease for Autonomic Symptoms, respectively. Hierarchical multiple regression analysis was used to investigate the correlations between abnormal iron metabolism and NMS. No differences in serum ceruloplasmin and ferritin levels were examined between PD patients and healthy controls, but we observed significantly decreased serum iron levels and increased serum transferrin levels in PD patients in comparison with healthy controls. After eliminating confounding factors, HAMD scores and HAMA scores were both negatively correlated with serum iron levels and positively correlated with serum transferrin levels. In summary, abnormal iron metabolism might play a crucial role in the pathogenesis of depression and anxiety in PD. Serums levels of iron and transferrin could be peripheral markers for depression and anxiety in PD.

Oxygen-enriched fermentation of sodium gluconate by Aspergillus niger and its impact on intracellular metabolic flux distributions.

Different concentrations of oxygen-enriched air were utilized for sodium gluconate (SG) fermentation by Aspergillus niger. The fermentation time shortened from 20 to 15.5 h due to the increase of volumetric oxygen transfer coefficient (KLa) and the formation of more dispersed mycelia when inlet oxygen concentration ascended from 21 to 32%. According to metabolic flux analysis, during the growth phase, extracellular glucose for SG synthesis accounted for 79.0 and 85.3% with air and oxygen-enriched air (25%), respectively, whereas the proportions were 89.4 and 93.0% in the stationary phase. Intracellular glucose consumption decreased in oxygen-enriched fermentation, as cell respiration was more high-efficiently performed. Metabolic profiling indicated that most intermediates in TCA cycle and EMP pathway had smaller pool sizes in oxygen-enriched fermentations. Moreover, the main by-product of citric acid dramatically decreased from 1.36 to 0.34 g L-1 in oxygen-enriched fermentation. And the sodium gluconate yield increased from 0.856 to 0.903 mol mol-1.

Kinetic analysis of sodium gluconate production by Aspergillus niger with different inlet oxygen concentrations.

To further understand fermentation kinetics of sodium gluconate (SG) production by Aspergillus niger with different inlet oxygen concentrations, logistic model for cell growth and two-step models for SG production and glucose consumption were established. The results demonstrated that the maximum specific growth rate (µm) presented exponential relationship with inlet oxygen concentration and the maximum biomass (Xm) exhibited linear increase. In terms of SG production, two-step model with Luedeking-Piret equation during growth phase and oxygen-dependent equation during stationary phase could well fit the experimental data. Notably, high inlet oxygen concentration exponentially improved SG yield (YP/S), whereas biomass yield to glucose (YX/S) and cell maintenance coefficient (m) were almost independent on inlet oxygen concentration, indicating that high oxygen supply enhancing SG synthesis not only functioning as a substrate directly, but also regulating glucose metabolism towards SG formation. Finally, the applicability and predictability of the proposed models were further validated by additional experiments.

Electron Beam Etching of CaO Crystals Observed Atom by Atom.

With the rapid development of nanoscale structuring technology, the precision in the etching reaches the sub-10 nm scale today. However, with the ongoing development of nanofabrication the etching mechanisms with atomic precision still have to be understood in detail and improved. Here we observe, atom by atom, how preferential facets form in CaO crystals that are etched by an electron beam in an in situ high-resolution transmission electron microscope (HRTEM). An etching mechanism under electron beam irradiation is observed that is surprisingly similar to chemical etching and results in the formation of nanofacets. The observations also explain the dynamics of surface roughening. Our findings show how electron beam etching technology can be developed to ultimately realize tailoring of the facets of various crystalline materials with atomic precision.

Triphenyltin chloride induces spindle microtubule depolymerisation and inhibits meiotic maturation in mouse oocytes.

Meiosis produces haploid gametes for sexual reproduction. Triphenyltin chloride (TPTCL) is a highly bioaccumulated and toxic environmental oestrogen; however, its effect on oocyte meiosis remains unknown. We examined the effect of TPTCL on mouse oocyte meiotic maturation in vitro and in vivo. In vitro, TPTCL inhibited germinal vesicle breakdown (GVBD) and first polar body extrusion (PBE) in a dose-dependent manner. The spindle microtubules completely disassembled and the chromosomes condensed after oocytes were exposed to 5 or 10µgmL(-1) TPTCL. γ-Tubulin protein was abnormally localised near chromosomes rather than on the spindle poles. In vivo, mice received TPTCL by oral gavage for 10 days. The general condition of the mice deteriorated and the ovary coefficient was reduced (P<0.05). The number of secondary and mature ovarian follicles was significantly reduced by 10mgkg(-1) TPTCL (P<0.05). GVBD decreased in a non-significant, dose-dependent manner (P>0.05). PBE was inhibited with 10mgkg(-1) TPTCL (P<0.05). The spindles of in vitro and in vivo metaphase II oocytes were disassembled with 10mgkg(-1) TPTCL. These results suggest that TPTCL seriously affects meiotic maturation by disturbing cell-cycle progression, disturbing the microtubule cytoskeleton and inhibiting follicle development in mouse oocytes.

Scutellaria barbata inhibits angiogenesis through downregulation of HIF-1 α in lung tumor.

Hypoxia, a hallmark of many solid tumors, is associated with angiogenesis and tumor progression. Hypoxia-inducible factor-1 (HIF-1) plays a significant role in tumor angiogenesis. In this study, the authors constructed a selective platform to screen the traditional Chinese medicine as anti-angiogenic agent. The authors examined the molecular mechanism by which Scutellaria barbata regulates HIF-1-dependent expression of vascular endothelial growth factor (VEGF), which is an important angiogenic factor. Hypoxia promotes angiogenesis by increasing VEGF expression and secretion. Herein, the expression of VEGF was decreased by treatment with S. barbata in tumor cells. Meanwhile, S. barbata reduced the migration and proliferation of endothelial cells under hypoxic condition. S. barbata inhibited the expression of HIF-1α, as well as phosphorylated their upstream signal mediators AKT. S. barbata significantly inhibited the tumor growth in vivo and immunohistochemical studies in the tumors revealed decreased intratumoral microvessel density. These results suggest that the traditional Chinese medicine therapy using S. barbata, which exerts anti-angiogenic activities, represents a promising strategy for the treatment of tumors.

The impact of quetiapine monotherapy or in combination with lithium on the thyroid function in patients with bipolar depression: A retrospective study.

OBJECTIVE: This study aims to investigate whether quetiapine monotherapy or in combination with lithium significantly disturbs thyroid function in depressed patients with bipolar disorder (BD), and whether difference exists in the post-treatment thyroid function between the two therapies. METHODS: Based on the electric medical records, outpatients and inpatients with a current depressive episode of BD from January 2016 to December 2022 were screened. All patients were treated with quetiapine monotherapy or in combination with lithium. In addition to the demographic data and depression scale, thyroid profiles including total thyroxine (TT4), total triiodothyronine (TT3), free thyroxine (FT4), free triiodothyronine (FT3), thyroid-stimulating hormone (TSH), thyroid peroxidase antibody (TPOAb), and antithyroglobulin antibody (TGAb) were recorded, analyzed, and compared before and after the treatment. RESULTS: Totally, 73 eligible patients were enrolled, including 53 in the monotherapy group (MG) and 20 in the combined therapy group (CG). No significant differences in thyroid profiles were detected between the two groups at the baseline (p > 0.05). After one-month treatment, in the MG, serum levels of TT4, TT3, FT4, and FT3 reduced significantly (p < 0.05), while TSH, TPOAb, and TGAb increased significantly (p < 0.05). In the CG, serum levels of TT4, TT3, and FT4 reduced and TSH increased following one-month treatment (p < 0.05), with no significant change in FT3, TPOAb, or TGAb (p > 0.05). After one-month treatment, no difference of TT4, TT3, FT4, FT3, and TSH was found between the two groups (p > 0.05). CONCLUSION: Both quetiapine monotherapy and a combined therapy with lithium significantly disturbed thyroid function in patients with bipolar depression, while quetiapine monotherapy seems to be associated with immune dysregulation in the thyroid.

Gradient-based adaptive wavelet de-noising method for photoacoustic imaging in vivo.

Photoacoustic imaging (PAI) has been applied to many biomedical applications over the past decades. However, the received PA signal usually suffers from poor SNR. Conventional solution of employing higher-power laser, or doing long-time signal averaging, may raise the system cost, time consumption, and tissue damage. Another strategy is de-noising algorithm design. In this paper, we propose a gradient-based adaptive wavelet de-noising method, which sets the energy gradient mutation point of low-frequency wavelet components as the threshold. We conducted simulation, ex-vivo and in-vivo experiments using acoustic-resolution PAM. The quality of de-noised PA image/signal by our proposed algorithm has improved by at least 30%, in comparison to the traditional signal denoising algorithms, which produces better contrast and clearer details. Moreover, it produces good results when dealing with multi-layer structures. The proposed de-noising method provides potential to improve the SNR of PA signal under single-shot low-power laser illumination for biomedical applications in vivo.

Photoacoustic imaging plus X: a review.

Significance: Photoacoustic (PA) imaging (PAI) represents an emerging modality within the realm of biomedical imaging technology. It seamlessly blends the wealth of optical contrast with the remarkable depth of penetration offered by ultrasound. These distinctive features of PAI hold tremendous potential for various applications, including early cancer detection, functional imaging, hybrid imaging, monitoring ablation therapy, and providing guidance during surgical procedures. The synergy between PAI and other cutting-edge technologies not only enhances its capabilities but also propels it toward broader clinical applicability. Aim: The integration of PAI with advanced technology for PA signal detection, signal processing, image reconstruction, hybrid imaging, and clinical applications has significantly bolstered the capabilities of PAI. This review endeavor contributes to a deeper comprehension of how the synergy between PAI and other advanced technologies can lead to improved applications. Approach: An examination of the evolving research frontiers in PAI, integrated with other advanced technologies, reveals six key categories named "PAI plus X." These categories encompass a range of topics, including but not limited to PAI plus treatment, PAI plus circuits design, PAI plus accurate positioning system, PAI plus fast scanning systems, PAI plus ultrasound sensors, PAI plus advanced laser sources, PAI plus deep learning, and PAI plus other imaging modalities. Results: After conducting a comprehensive review of the existing literature and research on PAI integrated with other technologies, various proposals have emerged to advance the development of PAI plus X. These proposals aim to enhance system hardware, improve imaging quality, and address clinical challenges effectively. Conclusions: The progression of innovative and sophisticated approaches within each category of PAI plus X is positioned to drive significant advancements in both the development of PAI technology and its clinical applications. Furthermore, PAI not only has the potential to integrate with the above-mentioned technologies but also to broaden its applications even further.