Nanopore Deciphering Single Digital Polymers Towards High-Density Data Storage.

Sequence-defined polymer is one of the most promising alternative media for high-density data storage. It could be used to alleviate the problem of insufficient storage capacity of conventional silicon-based devices for the explosively increasing data. To fulfil the goal of polymer data storage, suitable methods should be developed to accurately read and decode the information-containing polymers, especially for those composed by a combination of the natural and unnatural monomers. Nanopore-based approaches have become one of the most competitive analysis and sequencing techniques, which are expected to read both natural and synthetic polymers with single-molecule precision and monomeric resolution. Herein, this work emphasizes the advances being made in nanopore reading and decoding of information stored in the man-made polymers and DNA nanostructures, and discusses the challenges and opportunities towards the development and realization of high-density data storage.

A meta-analysis of the efficacy of Roux-en-Y anastomosis and jejunal interposition after total gastrectomy.

BACKGROUND: To compare the clinical efficacy of two alimentary tract reconstruction methods-"P"-shape jejunal interposition (PJI) and Roux-en-Y anastomosis after total gastrectomy. METHOD: The following search phrases were utilized to search PubMed, Cochrane Library, Embase, China Academic Journals Network Full-text Database (CNKI), and Wanfang Database as of April 2022: "gastrectomy," "Roux-en-Y," "interposition," "total gastrectomy," and "jejunal interposition." Meta-analysis of the operation time, intraoperative blood loss, complication rate, and postoperative nutritional status of patients was performed using RevMan 5.4 software. RESULTS: A total of 24 studies and 1887 patients were included in the study. Among patients who received a total gastrectomy, the operation time in the PJI group was substantially longer than that in the Roux-en-Y group (WMD = 19.77, 95% CI: 5.84-33.70, P = 0.005). The incidence of postoperative reflux esophagitis in the PJI group was considerably reduced than that in the Roux-en-Y group (OR = 0.39, 95% CI: 0.28-0.56, P < 0.01). The probability of postoperative dumping syndrome in the PJI group was significantly lower than that in the Roux-en-Y group (OR = 0.27, 95% CI: 0.17-0.43, P < 0.01), and the postoperative body mass changes were significantly lower in the PJI group than in the Roux-en-Y group (WMD = 3.94, 95% CI: 2.24-5.64, P < 0.01). The PJI group had substantially higher postoperative hemoglobin, albumin, and total protein levels than the Roux-en-Y group (WMD = 13.94, 95% CI: 7.77-19.20, P < 0.01; WMD = 3.97, 95% CI: 2.58-5.37, P < 0.01; WMD = 5.31, 95% CI: 3.45-7.16, P < 0.01). The prognostic nutritional index was higher in the PJI group than in the Roux-en-Y group (WMD = 9.25, 95% CI: 7.37-11.13, P < 0.01). CONCLUSION: PJI is a safe and effective reconstruction method and is superior to Roux-en-Y anastomosis in the prevention and treatment of postoperative complications and postoperative nutritional recovery in patients after total gastrectomy.

Time delay effect in a microchip pulse laser for the nonlinear photoacoustic signal enhancement.

The Grüneisen relaxation effect has been successfully employed to improve the photoacoustic (PA) imaging contrast. However, complex system design and cost hinder the progress from benchside to bedside, since an additional pre-heating laser source needs to be coupled into the original light path and synchronized with other equipment for conducting the nonlinear effect. To overcome the limitation, we propose a time delay heating PA imaging (TDH-PAI) method based on the time delay effect in a passively Q-switched laser. Experimentally, only one single microchip pulse laser is built and utilized for the nonlinear PA signal enhancement without additional components. The 808 nm pump pulse of the laser diode and the excited 1064 nm pulse are respectively used for pre-heating and acquiring PA signals. The heating effect is optimized by adjusting the input parameters and an enhancement of more than 30% in PA signals is achieved. TDH-PAI reduces the cost and complexity of the nonlinear PA system, which provides an efficient way for achieving a high-contrast PA imaging.

Low-intensity walking as mild medication for pressure control in prehypertensive and hypertensive subjects: how far shall we wander?

Successful prevention and treatment of hypertension depend on the appropriate combination of antihypertensive drug therapy and nondrug lifestyle modification. While most hypertension guidelines recommend moderate- to high-intensity exercise, we decided to explore a mild yet effective type of exercise to add to hypertension management, especially in populations with complications or frailty. After comparing the short-term cardiovascular effects of low-speed walking versus high-speed walking for 3 kilometers (km) (3 km/h versus 6 km/h) in young, healthy volunteers, we delivered low-speed walking (low-intensity walking, 2.5 metabolic equivalents of task, METs) as exercise therapy in 42 prehypertensive and 43 hypertensive subjects. We found that one session of 3 km low-intensity walking exerted a transient pressure-lowering effect as well as a mild negative chronotropic effect on heart rate in both the prehypertensive and hypertensive subjects; these short-term benefits on blood pressure and heart rate were accompanied by a brief increase in urine ß-endorphin output. Then we prescribed regular low-intensity walking with a target exercise dose (exercise volume) of 500-1000 METs·min/week (50-60 min/day and 5-7 times/week) in hypertensive subjects in addition to their daily activities. Regular low-intensity walking also showed mild but significant blood pressure-lowering and heart rate-reducing effects in 7 hypertensive subjects within two months. It is hypothesized that regular low-intensity exercise of the necessary dose could be taken as a pragmatic and supplementary medication for hypertension management.

A Handheld Real-Time Photoacoustic Imaging System for Animal Neurological Disease Models: From Simulation to Realization.

This article provides a guide to design and build a handheld, real-time photoacoustic (PA) imaging system from simulation to realization for animal neurological disease models. A pulsed laser and array-based ultrasound (US) platform were utilized to develop the system for evaluating vascular functions in rats with focal ischemia or subcutaneous tumors. To optimize the laser light delivery, finite element (FE)-based simulation models were developed to provide information regarding light propagation and PA wave generation in soft tissues. Besides, simulations were also conducted to evaluate the ideal imaging resolution of the US system. As a result, a PA C-scan image of a designed phantom in 1% Lipofundin was reconstructed with depth information. Performance of the handheld PA system was tested in an animal ischemia model, which revealed that cerebral blood volume (CBV) changes at the cortical surface could be monitored immediately after ischemia induction. Another experiment on subcutaneous tumors showed the anomalous distribution of the total hemoglobin concentration (HbT) and oxygen saturation (SO2), while 3D and maximum intensity projection (MIP) PA images of the subcutaneous tumors are also presented in this article. Overall, this system shows promise for monitoring disease progression in vascular functional impairments.

Encapsulated Conjugated Oligomer Nanoparticles for Real-Time Photoacoustic Sentinel Lymph Node Imaging and Targeted Photothermal Therapy.

Noninvasive and nonionizing imaging of sentinel lymph nodes (SLN) is highly desirable for the detection of breast cancer metastasis through sentinel lymph node biopsy. Photoacoustic (PA) imaging is an emerging imaging technique that can serve as a suitable approach for SLN imaging. Herein, novel conjugated oligomer based nanoparticles (NPs) with strong NIR absorption, good biocompatibility, excellent PA contrast, and good photothermal conversion efficiency are reported. Real-time PA imaging of SLN reveals high resolution of the NPs via injection from the left forepaw pad. In addition, the surface functionalized NPs can target breast cancer cells and kill them efficiently and specifically through photothermal therapy upon 808 nm laser irradiation. This work shows great potential of the nanoparticle PA contrast agent to serve as a multifunctional probe for photothermal therapy at SLNs to achieve the inhibition of cancer cell metastasis in the near future.

CagA promotes proliferation and secretion of extracellular matrix by inhibiting signaling pathway of apoptosis in rat glomerular mesangial cells.

Cytotoxin-associated antigen A (CagA), a major virulence factor of Helicobacter pylori (Hp), is associated with the pathogenesis of peptic ulcer and gastric cancer. Recent researches demonstrated that Hp exists in palatine tonsil in all studied IgA nephropathy (IgAN) patients, most of which were CagA-positive, suggesting that CagA may be a causative pathogenic factor of IgAN. However, the underlying molecular mechanisms and signaling pathway are still largely unclear. In the present study, CCK8 assay, enzyme-linked immunosorbent assay, and immunohistochemistry were performed to investigate the effect of CagA on cell proliferation and extracellular matrix secretion in rat glomerular mesangial cells. RT-PCR and western blotting were used to reveal the potential signaling pathway. Rat glomerular mesangial cells were treated with recombinant CagA protein for 72 h, in a dose- and time-dependent manner. We found that CagA promoted cell proliferation and extracellular matrix secretion by inhibiting signaling pathway of apoptosis. Taken together, these findings suggested that CagA induced cellular injury in glomerular mesangium by proliferation and secretion of extracellular matrix, and may play an important role in pathogenesis of IgAN.

Rescue of cortical neurovascular functions during the hyperacute phase of ischemia by peripheral sensory stimulation.

To investigate the potential therapeutic effects of peripheral sensory stimulation during the hyperacute phase of stroke, the present study utilized electrophysiology and photoacoustic imaging techniques to evaluate neural and vascular responses of the rat cortex following ischemic insult. We employed a rat model of photothrombotic ischemia (PTI), which targeted the forelimb region of the primary somatosensory cortex (S1FL), due to its high reproducibility in creating localized ischemic injury. We also established a hybrid, dual-modality system, including six-channel electrocorticography (ECoG) and functional photoacoustic microscopy (fPAM), termed ECoG-fPAM, to image brain functional responses to peripheral sensory stimulation during the hyperacute phase of PTI. Our results showed that the evoked cerebral blood volume (CBV) and hemoglobin oxygen saturation (SO2) recovered to 84±7.4% and 79±6.2% of the baseline, respectively, when stimulation was delivered within 2.5 h following PTI induction. Moreover, neural activity significantly recovered, with 77±8.6%, 76±5.3% and 89±8.2% recovery for the resting-state inter-hemispheric coherence, alpha-to-delta ratio (ADR) and somatosensory evoked potential (SSEP), respectively. Additionally, we integrated the CBV or SO2 with ADR values as a recovery indicator (RI) to assess functional recovery after PTI. The RI indicated that 80±4.2% of neurovascular function was preserved when stimulation was delivered within 2.5h. Additionally, stimulation treatment within this optimal time window resulted in a minimal infarct volume in the ischemic hemisphere (4.6±2.1%). In contrast, the infarct volume comprised 13.7±1.7% of the ischemic hemisphere when no stimulation treatment was applied.

Assessment of neurovascular dynamics during transient ischemic attack by the novel integration of micro-electrocorticography electrode array with functional photoacoustic microscopy.

This study developed a novel system combining a 16-channel micro-electrocorticography (µECoG) electrode array and functional photoacoustic microscopy (fPAM) to examine changes in neurovascular functions following transient ischemic attack (TIA) in rats. To mimic the pathophysiology of TIA, a modified photothrombotic ischemic model was developed by using 3 min illumination of 5 mW continuous-wave (CW) green laser light focusing on a distal branch of the middle cerebral artery (MCA). Cerebral blood volume (CBV), hemoglobin oxygen saturation (SO2), somatosensory evoked potentials (SSEPs) and alpha-to-delta ratio (ADR) were measured pre- and post-ischemia over a focal cortical region (i.e., 1.5×1.5 mm(2)). Unexpectedly, the SO2, peak-to-peak amplitude (PPA) of SSEPs and ADR recovered and achieved levels greater than the baseline values at the 4th hour post-ischemia induction without any intervention, whereas the CBV value only partially recovered. In other words, transient ischemia led to increased neural activity when the relative CBV was reduced, which may further compromise neural integrity or lead to subsequent vascular disease. This novel µECoG-fPAM system complements currently available imaging techniques and represents a promising technology for studying neurovascular coupling in animal models.

Recent progress in voltage-sensitive dye imaging for neuroscience.

Voltage-sensitive dye imaging (VSDi) enables visualization of information processing in different areas of the brain with reasonable spatial and temporal resolution. VSDi employs different chemical compounds to transduce neural activity directly into the changes in intrinsic optical signal. Physically, voltage-sensitive dyes (VSDs) are chemical probes that reside in the neural membrane and change their fluorescence or absorbance in response to membrane potential changes. Based on these features, VSDs can be divided into two groups-absorbance and fluorescence. The spatial and temporal resolution of the VSDi is limited mainly by the technical characteristics of the optical imaging setup (e.g., computer and light-sensitive device-charge-coupled device (CCD) camera or photodiode array). In this article, we briefly review the development of the VSD, technique of VSDi and applications in functional brain imaging.

Genome-wide analysis of Panonychus citri microRNAs with a focus on potential insecticidal activity of 4 microRNAs to eggs and nymphs.

Panonychus citri McGregor (Acari: Tetranychidae), a destructive citrus pest, causes considerable annual economic losses due to its short lifespan and rapid resistance development. MicroRNA (miRNA)-induced RNA interference is a promising approach for pest control because of endogenous regulation of pest growth and development. To search for miRNAs with potential insecticidal activity in P. citri, genome-wide analysis of miRNAs at different developmental stages was conducted, resulting in the identification of 136 miRNAs, including 73 known and 63 novel miRNAs. A total of 17 isomiRNAs and 12 duplicated miRNAs were characterized. MiR-1 and miR-252-5p were identified as reference miRNAs for P. citri and Tetranychus urticae. Based on differential expression analysis, treatments with miR-let-7a and miR-315 mimics and the miR-let-7a antagomir significantly reduced the egg hatch rate and resulted in abnormal egg development. Overexpression or downregulation of miR-34-5p and miR-305-5p through feeding significantly decreased the adult eclosion rate and caused molting defects. The 4 miRNAs, miR-let-7a, miR-315, miR-34-5p, and miR-305-5p, had important regulatory functions and insecticidal properties in egg hatching and adult eclosion. In general, these data advance our understanding of miRNAs in mite biology, which can assist future studies on insect-specific miRNA-based green pest control technology.

A 0D hybrid lead-free halide with near-unity photoluminescence quantum yield toward multifunctional optoelectronic applications.

Zero-dimensional (0D) hybrid metal halides have emerged as highly efficient luminescent materials, but integrated multifunction in a structural platform remains a significant challenge. Herein, a new hybrid 0D indium halide of (Im-BDMPA)InCl6·H2O was designed as a highly efficient luminescent emitter and X-ray scintillator toward multiple optoelectronic applications. Specifically, it displays strong broadband yellow light emission with near-unity photoluminescence quantum yield (PLQY) through Sb3+ doping, acting as a down-conversion phosphor to fabricate high-performance white light emitting diodes (WLEDs). Benefiting from the high PLQY and negligible self-absorption characteristics, this halide exhibits extraordinary X-ray scintillation performance with a high light yield of 55 320 photons per MeV, which represents a new scintillator in 0D hybrid indium halides. Further combined merits of a low detection limit (0.0853 µGyair s-1), ultra-high spatial resolution of 17.25 lp per mm and negligible afterglow time (0.48 ms) demonstrate its excellent application prospects in X-ray imaging. In addition, this 0D halide also exhibits reversible luminescence off-on switching toward tribromomethane (TBM) but fails in any other organic solvents with an ultra-low detection limit of 0.1 ppm, acting as a perfect real-time fluorescent probe to detect TBM with ultrahigh sensitivity, selectivity and repeatability. Therefore, this work highlights the multiple optoelectronic applications of 0D hybrid lead-free halides in white LEDs, X-ray scintillation, fluorescence sensors, etc.

Scanning optoacoustic angiography for assessing structural and functional alterations in superficial vasculature of patients with post-thrombotic syndrome: A pilot study.

This study highlights the potential of scanning optoacoustic angiography (OA) in identifying alterations of superficial vasculature in patients with post-thrombotic syndrome (PTS) of the foot, a venous stress disorder associated with significant morbidity developing from long-term effects of deep venous thrombosis. The traditional angiography methods available in the clinics are not capable of reliably assessing the state of peripheral veins that provide blood outflow from the skin, a key hallmark of personalized risks of PTS formation after venous thrombosis. Our findings indicate that OA can detect an increase in blood volume, diameter, and tortuosity of superficial blood vessels. The inability to spatially separate vascular plexuses of the dermis and subcutaneous adipose tissue serves as a crucial criterion for distinguishing PTS from normal vasculature. Furthermore, our study demonstrates the ability of scanning optoacoustic angiography to detect blood filling decrease in an elevated limb position versus increase in a lowered position.

Imaging of temperature dependent hemodynamics in the rat sciatic nerve by functional photoacoustic microscopy.

BACKGROUND: Vascular hemodynamics is central to the regulation of neuro-metabolism and plays important roles in peripheral nerves diseases and their prevention. However, at present there are only a few techniques capable of directly measuring peripheral nerve vascular hemodynamics. METHOD: Here, we investigate the use of dark-field functional photoacoustic microscopy (fPAM) for intrinsic visualizing of the relative hemodynamics of the rat sciatic nerve in response to localized temperature modulation (i.e., cooling and rewarming). RESULTS AND CONCLUSION: Our main results show that the relative functional total hemoglobin concentration (HbT) is more significantly correlated with localized temperature changes than the hemoglobin oxygen saturation (SO2) changes in the sciatic nerve. Our study also indicates that the relative HbT changes are better markers of neuronal activation than SO2 during nerve temperature changes. Our results show that fPAM is a promising candidate for in vivo imaging of peripheral nerve hemodynamics without the use of contrast agents. Additionally, this technique may shed light on the neuroprotective effect of hypothermia on peripheral nerves by visualizing their intrinsic hemodynamics.

Simultaneous Functional Magnetic Resonance and Optoacoustic Imaging of Brain-Wide Sensory Responses in Mice.

Functional magnetic resonance imaging (fMRI) has massively contributed to the understanding of mammalian brain function. However, the origin and interpretation of the blood oxygen level-dependent (BOLD) signals retrieved by fMRI remain highly disputed. This article reports on the development of a fully hybridized system enabling concurrent functional magnetic resonance optoacoustic tomography (MROT) measurements of stimulus-evoked brain-wide sensory responses in mice. The highly complementary angiographic and soft tissue contrasts of both modalities along with simultaneous multi-parametric readings of stimulus-evoked hemodynamic responses are leveraged in order to establish unequivocal links between the various counteracting physiological and metabolic processes in the brain. The results indicate that the BOLD signals are highly correlated, both spatially and temporally, with the total hemoglobin readings resolved with volumetric multi-spectral optoacoustic tomography. Furthermore, the differential oxygenated and deoxygenated hemoglobin optoacoustic readings exhibit superior sensitivity as compared to the BOLD signals when detecting stimulus-evoked hemodynamic responses. The fully hybridized MROT approach greatly expands the neuroimaging toolset to comprehensively study neurovascular and neurometabolic coupling mechanisms and related diseases.

Zero-Dimensional Hybrid Cuprous Halide of [BAPMA]Cu2Br5 as a Highly Efficient Light Emitter and an X-Ray Scintillator.

Lead halide perovskites have been explored as a new kind of promising X-ray with wide applications in radiation-associated fields, but low light yield and serious toxicity extremely restrict further applications. To address these issues, we herein demonstrated one new zero-dimensional (0D) organic-inorganic hybrid cuprous halide of [BAPMA]Cu2Br5 (BAPMA = N,N-Bis(3-aminopropyl) methylamine) containing discrete [Cu4Br10]6- tetramers as excellent lead-free scintillators. Upon UV light excitation, [BAPMA]Cu2Br5 displays highly efficient broadband yellowish-green light emission with one dominant peak at 526 nm, a large Stokes shift of 244 nm, and a high photoluminescent quantum yield of 53.40%. Significantly, this broadband light emission can also be excited by higher-energy X-ray as radioluminescence with a high scintillation light yield of 43,744 photons/MeV. The detection limit of 0.074 µGyair/s is also far less than the required value for regular medical diagnostics of 5.5 µGyair/s. The solution-assembled hybrid structure facilely enables the [BAPMA]Cu2Br5-based scintillation screen to display high-performance X-ray imaging with a spatial resolution of 15.79 lp/mm showcasing potential application in X-ray radiography. In brief, combined merits of low toxicity and cost, negligible self-absorption, a low detection limit, considerable light yield, and spatial resolution highlight the excellent scintillation performance of 0D hybrid cuprous halide.

Integrated oxidative stress score for predicting prognosis in stage III gastric cancer undergoing surgery.

Objective: This study aimed to develop a novel scoring system, named the integrated oxidative stress score (IOSS), based on oxidative stress indices to predict the prognosis in stage III gastric cancer. Methods: Retrospective analysis of stage III gastric cancer patients who were operated on between January 2014 and December 2016 were enrolled into this research. IOSS is a comprehensive index based on an achievable oxidative stress index, comprising albumin, blood urea nitrogen, and direct bilirubin. The patients were divided according to receiver operating characteristic curve into two groups of low IOSS (IOSS ≤ 2.00) and high IOSS (IOSS > 2.00). The grouping variable was performed by Chi-square test or Fisher's precision probability test. The continuous variables were evaluated by t-test. The disease free survival (DFS) and overall survival (OS) were performed by Kaplan-Meier and Log-Rank tests. Univariate Cox proportional hazards regression models and stepwise multivariate Cox proportional hazards regression analysis were determined to appraise the potential prognostic factors for DFS and OS. A nomogram of the potential prognostic factors by the multivariate analysis for DFS and OS was established with R software. In order to assess the accuracy of the nomogram in forecasting prognosis, the calibration curve and decision curve analysis were produced, contrasting the observed outcomes with the predicted outcomes. Results: The IOSS was significantly correlated with the DFS and OS, and was a potential prognostic factor in patients with stage III gastric cancer. Patients with low IOSS had longer survival (DFS: χ2 = 6.632, p = 0.010; OS: χ2 = 6.519, p = 0.011), and higher survival rates. According to the univariate and multivariate analyses, the IOSS was a potential prognostic factor. The nomograms were conducted on the potential prognostic factors to improve the correctness of survival prediction and evaluate the prognosis in stage III gastric cancer patients. The calibration curve indicated a good agreement in 1-, 3-, 5-year lifetime rates. The decision curve analysis indicated that the nomogram's predictive clinical utility for clinical decision was better than IOSS. Conclusion: IOSS is a nonspecific tumor predictor based on available oxidative stress index, and low IOSS is found to be a vigorous factor of better prognosis in stage III gastric cancer.

Immunoglobulin a vasculitis with testicular/epididymal involvement in children: A retrospective study of a ten-year period.

The clinical characteristics and risk factors for testicular/epididymal involvement in 73 children with immunoglobulin A vasculitis (IgAV) who were admitted to our hospital between January 2012 and November 2022 were reviewed. The demographic data, laboratory parameters, and follow-up data of the patients were compared to those of 146 males without testicular/epididymal involvement. A logistic regression analysis was performed to determine the variables associated with testicular/epididymal involvement. The prevalence of testicular/epididymal involvement among male patients with IgAV was 1.3% (73/5,556). Increased blood flow in the testes and/or epididymis on ultrasound was found in 71 patients. The remaining two patients underwent surgical exploration for loss or reduction of testicular blood flow. One patient underwent orchiectomy for intraoperative confirmation of complete right testicular infarction. Pathological findings revealed IgA immune complex deposition in the testis. Patient age (odds ratio [OR] = 0.792; 95% confidence interval [CI]: 0.682-0.919, p = 0.002), platelet count (OR = 1.011; 95% CI: 1.002-1.020, p = 0.013), and immunoglobulin M (IgM) levels (OR = 0.236; 95% CI: 0.091-0.608, p = 0.003) were strongly associated with the occurrence of testicular/epididymal involvement in IgAV. Therefore, young age, increased platelet count, and low IgM levels in patients with IgAV are potential risk factors for testicular/epididymal involvement. Doppler ultrasound can help differentiate IgAV from acute scrotum. Most patients with testicular/epididymal involvement have good prognoses, although serious complications such as testicular infarction may occur.

Reversible structural transformations and color-tunable emissions in organic manganese halides.

Herein, we for the first time report a reversible conversion between green-emissive [DMPZ]MnCl4 and red-emissive [DMPZ]4(MnCl6)(MnCl4)2·(H2O)2 (DMPZ = 1,4-dimethylpiperazine) using kinetic and thermodynamic controlling strategies. Significantly, the synchronous structural and emission transformations in single-component organic manganese halides with adjustable emission colors are highlighted.

Tracking Strain-Specific Morphogenesis and Angiogenesis of Murine Calvaria with Large-Scale Optoacoustic and Ultrasound Microscopy.

Skull bone development is a dynamic and well-coordinated process playing a key role in maturation and maintenance of the bone marrow (BM), fracture healing, and progression of diseases such as osteoarthritis or osteoporosis. At present, dynamic transformation of the growing bone (osteogenesis) as well as its vascularization (angiogenesis) remain largely unexplored due to the lack of suitable in vivo imaging techniques capable of noninvasive visualization of the whole developing calvaria at capillary-level resolution. We present a longitudinal study on skull bone development using ultrasound-aided large-scale optoacoustic microscopy (U-LSOM). Skull bone morphogenesis and microvascular growth patterns were monitored in three common mouse strains (C57BL/6J, CD-1, and Athymic Nude-Foxn1nu) at the whole-calvaria scale over a 3-month period. Strain-specific differences in skull development were revealed by quantitative analysis of bone and vessel parameters, indicating the coupling between angiogenesis and osteogenesis during skull bone growth in a minimally invasive and label-free manner. The method further enabled identifying BM-specific sinusoidal vessels, and superficial skull vessels penetrating into BM compartments. Our approach furnishes a new high-throughput longitudinal in vivo imaging platform to study morphological and vascular skull alterations in health and disease, shedding light on the critical links between blood vessel formation, skull growth, and regeneration. © 2022 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).