Heterogeneous Prototype Learning From Contaminated Faces Across Domains via Disentangling Latent Factors.

This article studies an emerging practical problem called heterogeneous prototype learning (HPL). Unlike the conventional heterogeneous face synthesis (HFS) problem that focuses on precisely translating a face image from a source domain to another target one without removing facial variations, HPL aims at learning the variation-free prototype of an image in the target domain while preserving the identity characteristics. HPL is a compounded problem involving two cross-coupled subproblems, that is, domain transfer and prototype learning (PL), thus making most of the existing HFS methods that simply transfer the domain style of images unsuitable for HPL. To tackle HPL, we advocate disentangling the prototype and domain factors in their respective latent feature spaces and then replacing the source domain with the target one for generating a new heterogeneous prototype. In doing so, the two subproblems in HPL can be solved jointly in a unified manner. Based on this, we propose a disentangled HPL framework, dubbed DisHPL, which is composed of one encoder-decoder generator and two discriminators. The generator and discriminators play adversarial games such that the generator embeds contaminated images into a prototype feature space only capturing identity information and a domain-specific feature space, while generating realistic-looking heterogeneous prototypes. Experiments on various heterogeneous datasets with diverse variations validate the superiority of DisHPL.

Assessing tobacco-related ischemic stroke in Pakistan (1990-2019): Insights from the Global Burden of Disease Study.

INTRODUCTION: This study analyzes the impact of active smoking and secondhand smoke on the ischemic stroke burden of Pakistan, 1990-2019. METHODS: We used data from the Global Burden of Disease (GBD) database to conduct a comprehensive evaluation of ischemic stroke-related indicators in Pakistan, including the number of deaths, mortality rates, disability-adjusted life years (DALYs), DALY rates, and the estimated annual percentage change (EAPC). Joinpoint analysis was applied to assess sex-specific temporal trends in the burden of active smoking and secondhand smoke in Pakistan and regions of Pakistan. These assessments incorporated the Socio-Demographic Index (SDI) and we have made comparative analyses of epidemiological differences between active smoking and secondhand smoke exposure. RESULTS: The burden of ischemic stroke related to tobacco use is presented in terms of the age-standardized mortality rate (ASMR) and the age-standardized disability-adjusted life year rate (ASDR) per 100000 population. The results (ASMR/ASDR) for Pakistan were 6.04/130.81, in the middle SDI region 7.69/176.54, and low-middle SDI region 5.64/124.22. Pakistan's ASMR is higher than the global average of 5.85, while ASDR is lower than the global average of 140.23. From 1990 to 2019, a downward trend in both ASMR and ASDR was observed, indicating progress in controlling tobacco-related stroke burdens. Individuals aged ≥70 years experienced the highest rates of stroke (ASMR: 66.31; ASDR: 1091.20). Gender disparities were evident: men were more affected by active smoking (ASMR: 3.08; ASDR: 78.47) than women (ASMR: 0.79; ASDR: 20.76), while women faced a higher burden from secondhand smoke (ASMR: 0.66; ASDR: 16.33) compared to men (ASMR: 0.79; ASDR: 9.93). Regional differences within Pakistan show fluctuating death and DALY rates. Notably, an increasing trend in female ASDR due to secondhand smoke in the Khyber Pakhtunkhwa Region (annual percentage change, APC=0.17 from 2010 to 2019) calls for focused health interventions. CONCLUSIONS: The study finds ASMR for tobacco-related ischemic stroke in Pakistan exceeds global averages, with significant gender and age disparities in exposure to smoke, highlighting the need for targeted health interventions.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation: publisher's note.

This publisher's note contains a correction to Opt. Lett.49, 674 (2024)10.1364/OL.509981.

Melatonin MT1 receptors regulate the Sirt1/Nrf2/Ho-1/Gpx4 pathway to prevent α-synuclein-induced ferroptosis in Parkinson's disease.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by the loss of dopaminergic (DA) neurons and aggregation of α-synuclein (α-syn). Ferroptosis, a form of cell death induced by iron accumulation and lipid peroxidation, is involved in the pathogenesis of PD. It is unknown whether melatonin receptor 1 (MT1) modulates α-syn and ferroptosis in PD. Here, we used α-syn preformed fibrils (PFFs) to induce PD models in vivo and in vitro. In PD mice, α-syn aggregation led to increased iron deposition and ferroptosis. MT1 knockout exacerbated these changes and resulted in more DA neuronal loss and severe motor impairment. MT1 knockout also suppressed the Sirt1/Nrf2/Ho1/Gpx4 pathway, reducing resistance to ferroptosis, and inhibited expression of ferritin Fth1, leading to more release of ferrous ions. In vitro experiments confirmed these findings. Knockdown of MT1 enhanced α-syn PFF-induced intracellular α-syn aggregation and suppressed expression of the Sirt1/Nrf2/Ho1/Gpx4 pathway and Fth1 protein, thereby aggravating ferroptosis. Conversely, overexpression of MT1 reversed these effects. Our findings reveal a novel mechanism by which MT1 activation prevents α-syn-induced ferroptosis in PD, highlighting the neuroprotective role of MT1 in PD.

Continuous tuning of pulse parameters in a soliton fiber laser by adjusting the effect of nonlinear polarization rotation.

We demonstrate that through inserting a short length of highly birefringent small-core photonic crystal fiber (Hi-Bi SC-PCF) into a soliton fiber laser, the nonlinear polarization rotation effect in this laser can be manipulated, leading to continuous tuning of the output pulse parameters. In experiments, we observed that by adjusting the polarization state of light launched into the Hi-Bi SC-PCF and varying the cavity attenuation, the laser spectral width can be continuously tuned from ∼7.1 to ∼1.7 nm, corresponding to a pulse-width-tuning range from ∼350 fs to ∼1.56 ps. During the parameter tuning, the output pulses strictly follow the soliton area theory, giving an almost constant time-bandwidth-product of ∼0.31. This soliton fiber laser, being capable of continuous parameter tuning, could be applied as the seed source in ultrafast laser systems and may find some applications in nonlinear-optics and soliton-dynamics experiments.

The Osmolality and Hemolysis of High-Concentration Monoclonal Antibody Formulations.

PURPOSES: Highly concentrated monoclonal antibody (mAb) formulations for subcutaneous administration are becoming increasingly preferred within the biopharmaceutical industry for ease of use and improved patient compliance. A common phenomenon observed in the industry is that osmolality detected via freezing-point depression (FPD) in high-concentration mAb formulations is much higher than the theoretical concentrations, yet the occurrence of this phenomenon and its possible safety issues have been rarely reported. METHODS: The current study summarized theoretical osmolality of U.S. Food and Drug Administration approved high-concentration mAb formulations and evaluated effects of high osmolality on safety using hemolysis experiments for the first time. Two mAbs formulated at 150 mg/mL were used as models and configured into two isotonic solutions: a, a theoretically calculated molarity in the isotonic range (H) and b, an osmolality value measured via the FPD in the isotonic range (I). The H and I formulations of each mAb were individually subjected to hemolysis experiments, and the hemolysis rates of the two formulations of the same mAb were compared. Besides, the effect of mAb concentration on osmolality detected by FPD was explored as well. RESULTS: The results indicated that the hemolysis rates were similar between the H and I formulations of mAbs at the same sample addition volume, and the osmolality values increased approximately linearly with the increase in mAb concentration. CONCLUSIONS: High osmolality for high-concentration mAb formulations would not affect product safety and the excipients could be added at relatively high levels to maintain product stability, especially for labile products.

Inhibition of GluN2D-Containing NMDA Receptors Protects Dopaminergic Neurons against 6-OHDA-Induced Neurotoxicity via Activating ERK/NRF2/HO-1 Signaling.

Abnormal glutamate signaling is implicated in the heightened vulnerability of dopaminergic neurons in Parkinson's disease (PD). NMDA receptors are ion-gated glutamate receptors with high calcium permeability, and their GluN2D subunits are prominently distributed in the basal ganglia and brainstem nuclei. Previous studies have reported that dopamine depletion led to the dysfunctions of GluN2D-containing NMDA receptors in PD animal models. However, it remains unknown whether selective modulation of GluN2D could protect dopaminergic neurons against neurotoxicity in PD. In this study, we found that allosteric activation of GluN2D-containing NMDA receptors decreased the cell viability of MES23.5 dopaminergic cells and the GluN2D inhibitor, QNZ46, showed antioxidant effects and significantly relieved apoptosis in 6-OHDA-treated cells. Meanwhile, we demonstrated that QNZ46 might act via activation of the ERK/NRF2/HO-1 pathway. We also verified that QNZ46 could rescue abnormal behaviors and attenuate dopaminergic cell loss in a 6-OHDA-lesioned rat model of PD. Although the precise mechanisms underlying the efficacy of QNZ46 in vivo remain elusive, the inhibition of the GluN2D subunit should be a considerable way to treat PD. More GluN2D-selective drugs, which present minimal side effects and broad therapeutic windows, need to be developed for PD treatment in future studies.

Experimental studies on the core-structure dependence of backward Brillouin gain in solid-core photonic crystal fibers.

Stimulated Brillouin scattering (SBS) in solid-core photonic crystal fibers (PCFs) differs significantly from that in standard optical fibers due to the tight confinement of both optical and acoustic fields in their µm-sized fiber cores, as resultantly evident in their Brillouin gain spectra. Despite many theoretical studies based on either simplified models or numerical simulations, the structural dependency of Brillouin gain spectra in small-core PCFs has not been characterized comprehensively using PCFs with elaborated parameter controls. In this work we report a comprehensive characterization on the core-structure dependences of backward SBS effects in solid-core PCFs that are drawn with systematically varied core-diameter, revealing several key trends of the fiber Brillouin spectrum in terms of its gain magnitude, Brillouin shift and multi-peak structure, which have not been reported in detail previously. Our work provides some practical guidance on PCF design for potential applications like Brillouin fiber lasers and Brillouin fiber sensing.

Safety and efficacy of brivaracetam in children epilepsy: a systematic review and meta-analysis.

Background: Epilepsy is one of the most common neurological diseases, affecting people of any age. Although the treatments of epilepsy are more and more diverse, the uncertainty regarding efficacy and adverse events still exists, especially in the control of childhood epilepsy. Methods: We performed a systematic review and meta- analysis following the Cochrane Handbook and preferred reporting items for systematic reviews and meta-analyses (PRISMA) guidelines. Four databases including PubMed, Embase, Web of Science and Cochrane library were searched. Studies reporting the use of brivaracetam monotherapy or adjuvant therapy in children (aged ≤18 years) were eligible for inclusion. Each stage of the review was conducted by two authors independently. Random-effects models were used to combine effect sizes for the estimation of efficacy and safety. Results: A total of 1884 articles were retrieved, and finally 9 articles were included, enrolling 503 children with epilepsy. The retention rate of BRV treatment was 78% (95% CI: 0.64-0.91), the responder rate (reduction of seizure frequency ≥ 50%) was 35% (95% CI: 0.24-0.47), the freedom seizure rate (no seizure) was 18% (95% CI: 0.10-0.25), and the incidence rate of any treatment-emergent adverse events (TEAE) was 39% (95% CI: 0.09-0.68). The most common TEAE was somnolence, which had an incidence rate of 9% (95% CI: 0.07-0.12). And the incidence rate of mental or behavioral disorders was 12% (95% CI: 0.06-0.17). Conclusion: Our systematic review and meta-analysis showed that BRV seemed to be safe and effective in the treatment of childhood epilepsy.

Lesion patterns and mechanism analysis of acute contralateral ischemic stroke accompanying stenosis of unilateral extracranial internal carotid artery.

BACKGROUND: Previous studies on unilateral internal carotid artery occlusive disease have focused on the mechanisms of ipsilateral hemispheric stroke, and contralateral stroke is considered to be an accidental phenomenon. Little is known about the relationship between severe stenosis (including occlusion) of the unilateral extracranial segment of the internal carotid artery and contralateral cerebral stroke, and the infarct patterns and pathogenesis require further study. The purpose of this study was to investigate the clinical characteristics and pathogenesis of contralateral acute stroke with unilateral extracranial internal carotid artery stenosis (including occlusion). METHODS: Thirty-four patients were enrolled in this study, and all patients underwent routine clinical evaluation, including medical history, physical examination, laboratory tests, and various imaging evaluations. The morphological characteristics of diffusion-weighted magnetic resonance imaging were applied to determine infarct patterns. The etiological classification was confirmed according to the TOAST classification. RESULTS: There were six distinctive lesion patterns: small subcortical infarcts (six patients), large subcortical infarcts (one patient), diffuse infarcts (eight patients), multiple anterior circulation infarcts (eight patients), multiple posterior circulation infarcts (two patients), and multiple anterior and posterior circulation infarcts (nine patients). CONCLUSION: Diffuse and multiple infarcts were the most common topographic patterns in ischemic stroke contralateral to internal carotid artery stenosis or occlusion. Hemodynamic impairment of the contralateral hemisphere due to hypoperfusion and blood theft is regarded as the basis of stroke occurrence. Low ischemic tolerance and embolism are the main causes of acute ischemic stroke.

Docosahexaenoic acid promotes M2 microglia phenotype via activating PPARγ-mediated ERK/AKT pathway against cerebral ischemia-reperfusion injury.

In ischemia-reperfusion stroke, microglia play a dual role in brain injury as well as brain repair, and promoting their switch from a pro-inflammatory M1 phenotype to an anti-inflammatory M2 phenotype is considered to be a potential therapeutic strategy. Docosahexaenoic acid (DHA) is an essential long-chain omega-3 polyunsaturated fatty acid that exhibits potent anti-inflammatory properties in the acute phase of ischemic stroke, but its effect on microglia polarization is unknown. Thus, the objective of this study was to investigate the neuroprotective effects of DHA on rat brain following ischemia-reperfusion injury, and to investigate the mechanism by which DHA regulates microglia polarization. We administered DHA 5 mg/kg intraperitoneally daily for 3 d following a transient middle cerebral artery occlusion reperfusion model in rats. The protective effects of DHA on cerebral ischemia-reperfusion injury were detected by TTC staining, HE staining, Nissler staining, and TUNEL staining. Quantitative real-time PCR, immunofluorescence, western blot, and enzyme-linked immunosorbent assay were used to detect the expression of M1 and M2 microglia-associated markers and PPARγ-mediated ERK/AKT signaling pathway proteins. We found that DHA significantly improved brain injury by decreasing the expression of the M1 phenotypic marker (iNOS, CD16) and increasing the expression of the M2 phenotypic marker (Arg-1, CD206). DHA also increased the expression of peroxisome proliferator-activated receptor gamma (PPARγ) mRNA and protein, increased the expression of the pathway protein AKT, and decreased the expression of ERK1/2. In addition, DHA promoted the expression of anti-inflammatory factor IL-10 and decreased the expression of pro-inflammatory factors TNF-α and IL-1ß. However, the PPARγ antagonist GW9662 greatly blocked these beneficial effects. These results suggest that DHA may activate PPARγ to inhibit ERK and activate AKT signaling pathways to regulate microglia polarization, thereby reducing neuroinflammation and promoting neurological recovery to alleviate cerebral ischemia-reperfusion injury.

Highly stable, flexible delivery of microjoule-level ultrafast pulses in vacuumized anti-resonant hollow-core fibers for active synchronization.

We demonstrate the stable and flexible light delivery of multi-microjoule, sub-200-fs pulses over a ∼10-m-long vacuumized anti-resonant hollow-core fiber (AR-HCF), which was successfully used for high-performance pulse synchronization. Compared with the pulse train launched into the AR-HCF, the transmitted pulse train out of the fiber exhibits excellent stabilities in pulse power and spectrum, with pointing stability largely improved. The walk-off between the fiber-delivery and the other free-space-propagation pulse trains, in an open loop, was measured to be <6 fs root mean square (rms) over 90 minutes, corresponding to a relative optical-path variation of <2 × 10-7. This walk-off can be further suppressed to ∼2 fs rms simply by using an active control loop, highlighting the great application potentials of this AR-HCF setup in large-scale laser and accelerator facilities.

Auto Diagnosis of Parkinson's Disease Via a Deep Learning Model Based on Mixed Emotional Facial Expressions.

Parkinson's disease (PD) is a common degenerative disease of the nervous system in the elderly. The early diagnosis of PD is very important for potential patients to receive prompt treatment and avoid the aggravation of the disease. Recent studies have found that PD patients always suffer from emotional expression disorder, thus forming the characteristics of "masked faces". Based on this, we thus propose an auto PD diagnosis method based on mixed emotional facial expressions in the paper. Specifically, the proposed method is cast into four steps: Firstly, we synthesize virtual face images containing six basic expressions (i.e., anger, disgust, fear, happiness, sadness, and surprise) via generative adversarial learning, in order to approximate the premorbid expressions of PD patients; Secondly, we design an effective screening scheme to assess the quality of the above synthesized facial expression images and then shortlist the high-quality ones; Thirdly, we train a deep feature extractor accompanied with a facial expression classifier based on the mixture of the original facial expression images of the PD patients, the high-quality synthesized facial expression images of PD patients, and the normal facial expression images from other public face datasets; Finally, with the well-trained deep feature extractor, we thus adopt it to extract the latent expression features for six facial expression images of a potential PD patient to conduct PD/non-PD prediction. To show real-world impacts, we also collected a new facial expression dataset of PD patients in collaboration with a hospital. Extensive experiments are conducted to validate the effectiveness of the proposed method for PD diagnosis and facial expression recognition.

Role of α-synuclein in microglia: autophagy and phagocytosis balance neuroinflammation in Parkinson's disease.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disease, and is characterized by accumulation of α-synuclein (α-syn). Neuroinflammation driven by microglia is an important pathological manifestation of PD. α-Syn is a crucial marker of PD, and its accumulation leads to microglia M1-like phenotype polarization, activation of NLRP3 inflammasomes, and impaired autophagy and phagocytosis in microglia. Autophagy of microglia is related to degradation of α-syn and NLRP3 inflammasome blockage to relieve neuroinflammation. Microglial autophagy and phagocytosis of released α-syn or fragments from apoptotic neurons maintain homeostasis in the brain. A variety of PD-related genes such as LRRK2, GBA and DJ-1 also contribute to this stability process. OBJECTIVES: Further studies are needed to determine how α-syn works in microglia. METHODS: A keyword-based search was performed using the PubMed database for published articles. CONCLUSION: In this review, we discuss the interaction between microglia and α-syn in PD pathogenesis and the possible mechanism of microglial autophagy and phagocytosis in α-syn clearance and inhibition of neuroinflammation. This may provide a novel insight into treatment of PD.

DisP+V: A Unified Framework for Disentangling Prototype and Variation From Single Sample per Person.

Single sample per person face recognition (SSPP FR) is one of the most challenging problems in FR due to the extreme lack of enrolment data. To date, the most popular SSPP FR methods are the generic learning methods, which recognize query face images based on the so-called prototype plus variation (i.e., P+V) model. However, the classic P+V model suffers from two major limitations: 1) it linearly combines the prototype and variation images in the observational pixel-spatial space and cannot generalize to multiple nonlinear variations, e.g., poses, which are common in face images and 2) it would be severely impaired once the enrolment face images are contaminated by nuisance variations. To address the two limitations, it is desirable to disentangle the prototype and variation in a latent feature space and to manipulate the images in a semantic manner. To this end, we propose a novel disentangled prototype plus variation model, dubbed DisP+V, which consists of an encoder-decoder generator and two discriminators. The generator and discriminators play two adversarial games such that the generator nonlinearly encodes the images into a latent semantic space, where the more discriminative prototype feature and the less discriminative variation feature are disentangled. Meanwhile, the prototype and variation features can guide the generator to generate an identity-preserved prototype and the corresponding variation, respectively. Experiments on various real-world face datasets demonstrate the superiority of our DisP+V model over the classic P+V model for SSPP FR. Furthermore, DisP+V demonstrates its unique characteristics in both prototype recovery and face editing/interpolation.

1,25-D3 attenuates cerebral ischemia injury by regulating mitochondrial metabolism via the AMPK/AKT/GSK3ß pathway.

The brain injury caused by cerebral ischemia-reperfusion is related to mitochondrial damage. Maintaining the normal function of mitochondria, promoting angiogenesis, protecting neuronal cells, and resisting oxidative stress are the keys to functional recovery after acute ischemic stroke. In this study, we established a middle cerebral artery occlusion (MCAO) model and investigated the effects of 1α,25-dihydroxyvitamin D3 (VitD or 1,25-D3) on mitochondrial function via the adenosine 5'-monophosphate-activated protein kinase (AMPK)/protein kinase B (AKT)/glycogen synthase kinase-3ß (GSK-3ß) signaling pathway in rats with cerebral ischemia-reperfusion injury. The neurological function and infarct size were measured in each group. Hematoxylin-eosin, neuronal nucleus, and Nissl staining procedures were conducted to observe the morphology and number of the cerebral cortical neurons. Western blotting was then used to analyze p-AMPK, vitamin D receptor (VDR), p-GSK-3ß, p-AKT, P53, cytochrome C (CytC), TGF-ß, and vascular endothelial growth factor (VEGF) in mitochondria. Immunofluorescence staining was used to observe the expression of CytC and caspase-3. Succinate dehydrogenase, ATPase, reactive oxygen species, and malondialdehyde were detected by kits. RT-qPCR was used to analyze TGF-ß, VEGF, P53, and CytC mRNA. The results revealed that the cerebral infarct volume, neurological function score, apoptotic protein P53, CytC, caspase-3, reactive oxygen species, and malondialdehyde were significantly increased in MCAO rats. 1,25-D3 reduced the infarct size and neurological function score, activated VDR, upregulated TGF-ß, p-AMPK, p-AKT, p-GSK-3ß, VEGF, ATP, and succinate dehydrogenase, and downregulated P53, CytC, caspase-3, reactive oxygen species, and malondialdehyde. As an antagonist of VDRs, pyridoxal-5-phosphate could partially block the neuroprotective effect of 1,25-D3. In conclusion, 1,25-D3 activated AMPK/AKT/GSK-3ß signaling and VDRs, inhibited P53, CytC, and caspase-3, increased TGF-ß and VEGF, regulated mitochondrial metabolism, reduced neuronal apoptosis, promoted vascular growth, and exerted neuroprotective effects. These findings suggest that this signaling pathway may be an effective target for the treatment of ischemic stroke.

Measurements of microjoule-level, few-femtosecond ultraviolet dispersive-wave pulses generated in gas-filled hollow capillary fibers.

To the best of our knowledge, we demonstrate the first time-domain measurement of µJ-level, few-fs ultraviolet dispersive-wave (DW) pulses generated in gas-filled hollow capillary fibers (HCFs) in an atmosphere environment using several chirped mirrors. The pulse temporal profiles, measured using a self-diffraction frequency-resolved optical gating setup, exhibit full width at half maximum pulse widths of 9.6 fs at 384 nm and 9.4 fs at 430 nm, close to the Fourier-transform limits. Moreover, theoretical and experimental studies reveal the strong influences of driving pulse energy and HCF length on temporal width and shape of the measured DW pulses. The ultraviolet pulses obtained in an atmosphere environment with µJ-level pulse energy, few-fs pulse width, and broadband wavelength tunability are ready to be used in many applications.

Large evanescently-induced Brillouin scattering at the surrounding of a nanofibre.

Brillouin scattering has been widely exploited for advanced photonics functionalities such as microwave photonics, signal processing, sensing, lasing, and more recently in micro- and nano-photonic waveguides. Most of the works have focused on the opto-acoustic interaction driven from the core region of micro- and nano-waveguides. Here we observe, for the first time, an efficient Brillouin scattering generated by an evanescent field nearby a single-pass sub-wavelength waveguide embedded in a pressurised gas cell, with a maximum gain coefficient of 18.90 ± 0.17 m-1W-1. This gain is 11 times larger than the highest Brillouin gain obtained in a hollow-core fibre and 79 times larger than in a standard single-mode fibre. The realisation of strong free-space Brillouin scattering from a waveguide benefits from the flexibility of confined light while providing a direct access to the opto-acoustic interaction, as required in free-space optoacoustics such as Brillouin spectroscopy and microscopy. Therefore, our work creates an important bridge between Brillouin scattering in waveguides, Brillouin spectroscopy and microscopy, and opens new avenues in light-sound interactions, optomechanics, sensing, lasing and imaging.

Freeze-Dried Biopharmaceutical Formulations are Surprisingly Less Stable than Liquid Formulations during Dropping.

PURPOSES: This article describes an interesting phenomenon in which optimized freeze-dried (FD) biopharmaceutical formulations are generally more prone to degradation than their liquid counterparts during dropping and proposes an underlying cause for this surprising phenomenon. METHODS: Two monoclonal antibodies (mAbs) and a fusion protein (FP) were used as model biopharmaceuticals. The stability after dropping stress was determined by ultraviolet-visible (UV-Vis), size exclusion high-performance liquid chromatography (SE-HPLC), micro-flow imaging (MFI), and dynamic light scattering (DLS). RESULTS: Contrary to what we would normally assume, the FD formulations of the three biopharmaceuticals studied here generally showed much higher amounts of protein sub-visible particles (SbVPs) than liquid formulations after applying the same dropping stress as determined by MFI and DLS. Traditional techniques, such as UV-Vis and SE-HPLC, could hardly detect such degradation. CONCLUSIONS: We propose that the higher temperature caused by dropping for the FD powders than the liquid formulations was probably one of the root causes for the higher amount of particles formed for the FD powders. We also recommend that dropping stress should be included for early-stage screening and choosing liquid versus FD biopharmaceutical formulations.